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Meta-Analysis
. 2009 Jan 21;2009(1):CD006153.
doi: 10.1002/14651858.CD006153.pub2.

Treatment for familial amyotrophic lateral sclerosis/motor neuron disease

Michael Benatar  1 , Jerome Kurent, Dan H Moore
Affiliations
Meta-Analysis

Treatment for familial amyotrophic lateral sclerosis/motor neuron disease

Michael Benatar et al. Cochrane Database Syst Rev. .

Abstract

Background: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a rare neurodegenerative disease. Approximately 5% to 7% of ALS/MND patients report a family history of a similarly affected relative. Superoxide dismutase-1 gene mutations are the cause in about 20% of familial cases. In those with non-familial (sporadic) ALS/MND the cause is unknown. Also unknown is whether patients with familial and sporadic ALS/MND respond differently to treatment.

Objectives: To systematically review the literature and to answer the specific question: 'Is there a difference in the response to treatment between patients with sporadic and familial forms of ALS?'

Search strategy: In May 2006 we searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (January 1966 to May 2006) and EMBASE (January 1980 to May 2006) for randomized controlled trials (RCTs). Two review authors read the titles and abstracts of all articles and reviewed the full text of all possibly relevant articles. We scanned references of all included trials to identify additional relevant articles. For all trials eligible for inclusion we contacted the authors to request the necessary raw data.

Selection criteria: Studies had to meet two criteria: (a) randomized controlled study design, and (b) inclusion of patients with both familial and sporadic ALS/MND.

Data collection and analysis: We attempted to contact authors of all trials that met inclusion criteria. We obtained data regarding ALS/MND type (sporadic versus familial), treatment assignment (active versus placebo), survival and ALS Functional Rating Scale scores for four large RCTs that included 822 sporadic and 41 familial ALS patients. We could not obtain data from 25 potentially eligible studies (17 trial authors could not be contacted and eight were unwilling to provide data).

Main results: There was no statistical evidence for a different response to treatment in patients with familial ALS/MND compared to those with sporadic ALS/MND. The pooled estimate of the hazard ratio for the interaction term (treatment x familial ALS) suggested a more beneficial response with respect to survival among patients with familial ALS/MND, but the result was not statistically significant. Estimates of the rate of decline on the ALS Functional Rating Scale also suggested a slightly better response to treatment among those with familial ALS/MND, but the result was not statistically significant.

Authors' conclusions: Future RCTs should document whether patients with familial ALS/MND are included and the presence or absence of a mutation in the superoxide dismutase-1 gene amongst those with familial ALS/MND.

PubMed Disclaimer

Conflict of interest statement

Michael Benatar is the principal investigator of the ongoing randomized, double‐blind, placebo‐controlled of arimoclomol in SOD1 positive familial ALS. This trial is jointly funded by the ALS Association and the Food & Drug Administration.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Cudkowicz 2003 {published and unpublished data}
    1. Cudkowicz ME, Shefner JM, Schoenfeld DA, Brown RH Jr, Johnson H, Qureshi M, et al. A randomized, placebo‐controlled trial of topiramate in amyotrophic lateral sclerosis [see comment]. Neurology 2003;61(4):456‐64. [PUBMED: 12939417] - PubMed
Cudkowicz 2006 {published and unpublished data}
    1. Cudkowicz ME, Shefner JM, Schoenfeld DA, Zhang H, Andreasson KI, Rothstein JD, et al. Trial of celecoxib in amyotrophic lateral sclerosis. Annals of Neurology 2006;60(1):22‐31. [PUBMED: 16802291] - PubMed
Cudkowicz 2008 {published and unpublished data}
    1. Cudkowicz ME, Shefner JM, Simpson E, Grasso D, Yu H, Zhang H, et al. Arimoclomol at dosages up to 300mg/day is well tolerated and safe in amyotropic lateral sclerosis. Muscle and Nerve 2008;38(1):837‐844. [PUBMED: 18551622] - PubMed
Groeneveld 2003 {published and unpublished data}
    1. Groeneveld GJ, Veldink JH, Tweel I, Kalmijn S, Beijer C, Visser M, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Annals of Neurology 2003;53(4):437‐45. [PUBMED: 12666111 ] - PubMed
Shefner 2004 {published and unpublished data}
    1. Shefner JM, Cudkowicz ME, Schoenfeld D, Conrad T, Taft J, Chilton M, et al. A clinical trial of creatine in ALS. Neurology 2004;63(9):1656‐61. [PUBMED: 15534251] - PubMed

References to studies excluded from this review

Appel 1988 {published data only}
    1. Appel SH, Stewart SS, Appel V, Harati Y, Mietlowski W, Weiss W, et al. A double‐blind study of the effectiveness of cyclosporine in amyotrophic lateral sclerosis. Archives of Neurology 1988;45(4):381‐6. [PUBMED: 3281637] - PubMed
Askmark 1993 {published data only}
    1. Askmark H, Aquilonius SM, Gillberg PG, Liedholm LJ, Stålberg E, Wuopio R. A pilot trial of dextromethorphan in amyotrophic lateral sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 1993;56(2):197‐200. [PUBMED: 8437010] - PMC - PubMed
Beghi 1993 {published data only}
    1. Branched‐chain amino acids and amyotrophic lateral sclerosis: a treatment failure? The Italian Study Group. Neurology 1993;43(12):2466‐70. [PUBMED: 8255440] - PubMed
Beghi 2000 {published data only}
    1. Beghi E, Chiò A, Inghilleri M, Mazzini L, Micheli A, Mora G, et a. A randomized controlled trial of recombinant interferon beta‐1a in ALS. Italian Amyotrophic Lateral Sclerosis Study Group. Neurology 2000;54(2):469‐74. [PUBMED: 10668716] - PubMed
Bello‐Haas 2007 {published data only}
    1. Bello‐Haas VD, Florence JM, Kloos AD, Scheirbecker J, Lopate G, Hayes SM, et al. A randomized controlled trial of resistance exercise in individuals with ALS. Neurology 2007;68(23):2003‐7. [PUBMED: 17548549] - PubMed
Bensimon 1994 {published data only}
    1. Bensimon G, Lacomblez L, Meininger V, A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. New England Journal of Medicine 1994;330(9):585‐91. [PUBMED: 8302340] - PubMed
Bensimon 2002 {published data only}
    1. Bensimon G, Lacomblez L, Delumeau JC, Bejuit R, Truffinet P, Meininger V. Riluzole/ALS Study Group. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis.[see comment]. Journal of Neurology 2002;249(5):609‐15. [PUBMED: 12021952] - PubMed
Berto 2007 {published data only}
    1. Berto MC, Filha SC, Camelier A, Rosa FW, Souza Bulle Oliveira A, Jardim JR. Acute action of aminophylline in patients with amyotrophic lateral sclerosis. Acta Neurologica Scandinavica 2007;115(3):301‐5. [PUBMED: 17489939] - PubMed
Blin 1992 {published data only}
    1. Blin O, Pouget J, Aubrespy G, Guelton C, Crevat A, Serratrice G. A double‐blind placebo‐controlled trial of L‐threonine in amyotrophic lateral sclerosis. Journal of Neurology 1992;239(2):79‐81. [PUBMED: 1313078] - PubMed
Blin 1996 {published data only}
    1. Blin O, Azulay JP, Desnuelle C, Billé‐Turc F, Braguer D, Besse D, et al. A controlled one‐year trial of dextromethorphan in amyotrophic lateral sclerosis. Clinical Neuropharmacology 1996;19(2):189‐92. [PUBMED: 8777774] - PubMed
Borasio 1998 {published data only}
    1. Borasio GD, Robberecht W, Leigh PN, Emile J, Guiloff RJ, Jerusalem F, et al. A placebo‐controlled trial of insulin‐like growth factor‐I in amyotrophic lateral sclerosis. European ALS/IGF‐I Study Group. Neurology 1998;51(2):583‐6. [PUBMED: 9710040] - PubMed
Bourke 2006 {published data only}
    1. Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non‐invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial [see comment]. Lancet Neurology 2006;5(2):140‐7. [PUBMED: 16426990] - PubMed
Bradley 1984 {published data only}
    1. Bradley WG, Hedlund W, Cooper C, Desousa GJ, Gabbai A, Mora JS, et al. A double‐blind controlled trial of bovine brain gangliosides in amyotrophic lateral sclerosis. Neurology 1984;34(8):1079‐82. [PUBMED: 6379506] - PubMed
Brody 1974 {published data only}
    1. Brody JA, Chen KM, Yase Y, Holden EM, Morris CE. Inosiplex and amyotrophic lateral sclerosis. Therapeutic trial in patients on Guam. Archives of Neurology 1974;30(4):322‐3. [PUBMED: 4593550] - PubMed
Brooke 1986 {published data only}
    1. Brooke MH, Florence JM, Heller SL, Kaiser KK, Phillips D, Gruber A, et al. Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis. Neurology 1986;36(2):146‐51. [PUBMED: 3080694] - PubMed
Brooks 1985 {published data only}
    1. Brooks BR, Sufit RL, Beaulieu DA, Erickson LM, Montgomery GK, Peters HA, et al. Intravenous (10 mg/kg) thyrotropin releasing hormone (TRH) administration in amyotrophic lateral sclerosis (ALS): decreased loss of muscle strength in TRH‐treated patients during parallel‐placebo controlled pilot study. Journal of Neurology 1985;232:264.
Brooks 1996 {published data only}
    1. A double‐blind placebo‐controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 1996;46(5):1244‐9. [PUBMED: 8628460] - PubMed
Caroscio 1986 {published data only}
    1. Caroscio JT, Cohen JA, Zawodniak J, Takai V, Shapiro A, Blaustein S, et al. A double‐blind, placebo‐controlled trial of TRH in amyotrophic lateral sclerosis. Neurology 1986;36(2):141‐5. [PUBMED: 3080693] - PubMed
Chio 1998 {published data only}
    1. Chiò A, Cucatto A, Terreni AA, Schiffer D. Reduced glutathione in amyotrophic lateral sclerosis: an open, crossover, randomized trial. Italian Journal of Neurological Sciences 1998;19(6):363‐6. [PUBMED: 10935831] - PubMed
Desnuelle 2001 {published data only}
    1. Desnuelle C, Dib M, Garrel C, Favier A. A double‐blind, placebo‐controlled randomized clinical trial of alpha‐tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole‐tocopherol Study Group. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2001;2(1):9‐18. [PUBMED: 11465936] - PubMed
Drachman 1994 {published data only}
    1. Drachman DB, Chaudhry V, Cornblath D, Kuncl RW, Pestronk A, Clawson L, et al. Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation [see comment]. Annals of Neurology 1994;35(2):142‐50. [PUBMED: 8109895] - PubMed
Drory 2001 {published data only}
    1. Drory VE, Goltsman E, Goldman‐Reznick J, Mosek A. The value of muscle exercise in patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2001;187(Suppl 1):S125. - PubMed
Eisen 1993 {published data only}
    1. Eisen A, Stewart H, Schulzer M, Cameron D. Anti‐glutamate therapy in amyotrophic lateral sclerosis: a trial using lamotrigine. Canadian Journal of Neurological Sciences 1993;20(4):297‐301. [PUBMED: 7906190] - PubMed
Farkkila 1996 {published data only}
    1. Färkkilä M, Laaksovirta H, Hokkanen L, Cantell K. High‐dose alpha‐interferon treatment in amyotrophic lateral sclerosis. Biotechnologia Aplicada 1996;13(4).
Fornai 2008 {published data only}
    1. Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M, Manca M L, et al. Lithium delays progression of amyotrophic lateral sclerosis.[see comment][erratum appears in Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16404‐7]. Proceedings of the National Academy of Sciences of the United States of America 2008;105(6):2052‐7. [PUBMED: 18250315] - PMC - PubMed
Goonetilleke 1995 {published data only}
    1. Goonetilleke A, Guiloff R J. Continuous response variable trial design in motor neuron disease: long term treatment with a TRH analogue (RX77368). Journal of Neurology, Neurosurgery and Psychiatry 1995;58(2):201‐8. [PUBMED: 7876852] - PMC - PubMed
Gordon 2006 {published data only}
    1. Gordon PH, Doorish C, Montes J, Mosely RL, Diamond B, Macarthur RB, et al. Randomized controlled phase II trial of glatiramer acetate in ALS. Neurology 2006;66(7):1117‐9. [PUBMED: 16606934] - PubMed
Gordon 2007 {published data only}
    1. Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.[see comment]. Lancet Neurology 2007;6(12):1045‐53. [PUBMED: 17980667] - PubMed
Gordon 2008 {published data only}
    1. Gordon PH, Cheung YK, Levin B, Andrews H, Doorish C, MacArthur RB, et al. A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS. Amyotrophic Lateral Sclerosis 2008;9(4):212‐22. [PUBMED: 18608093] - PMC - PubMed
Graf 2005 {published data only}
    1. Graf M, Ecker D, Horowski R, Kramer B, Riederer P, Gerlach M, et al. High dose vitamin E therapy in amyotrophic lateral sclerosis as add‐on therapy to riluzole: results of a placebo‐controlled double‐blind study. Journal of Neural Transmission 2005;112(5):649‐60. [PUBMED: 15517433] - PubMed
Gredal 1997 {published data only}
    1. Gredal O, Werdelin L, Bak S, Christensen PB, Boysen G, Kristensen MO, et al. A clinical trial of dextromethorphan in amyotrophic lateral sclerosis. Acta Neurologica Scandinavica 1997;96(1):8‐13. [PUBMED: 9262126] - PubMed
Guiloff 1987 {published data only}
    1. Guiloff RJ, Eckland DJ, Demaine C, Hoare RC, MacRae KD, Lightman SL. Controlled acute trial of a thyrotrophin releasing hormone analogue (RX77368) in motor neuron disease. Journal of Neurology, Neurosurgery and Psychiatry 1987;50(10):1359‐70. [PUBMED: 3119776] - PMC - PubMed
Harrington 1984 {published data only}
    1. Harrington H, Hallett M, Tyler HR. Ganglioside therapy for amyotrophic lateral sclerosis: a double‐blind controlled trial. Neurology 1984;34(8):1083‐5. [PUBMED: 6379507] - PubMed
Hesselmans 1993 {published data only}
    1. Hesselmans LF, Wieneke GH, Oey PL, Groenhout DM, Graaf Y, Gispen WH, et al. Evaluation of electrophysiological and clinical tests in an exploratory trial of Org 2766 in motor neuron disease. Neuromuscular Disorders 1993;3(4):319‐25. [PUBMED: 8268729] - PubMed
Imoto 1984 {published data only}
    1. Imoto K, Saida K, Iwamura K, Saida T, Nishitani H. Amyotrophic lateral sclerosis: a double‐blind crossover trial of thyrotropin‐releasing hormone. Journal of Neurology, Neurosurgery and Psychiatry 1984;47(12):1332‐4. [PUBMED: 6439824] - PMC - PubMed
Janik 1996 {published data only}
    1. Janik P, Kwiecinski H, Jamrozik Z, Czyzewski K, Opuchlik A. A randomised trial of antioxidative therapy in amyotrophic lateral sclerosis. Journal of Neurology 1996;243:S25.
Jossan 1994 {published data only}
    1. Jossan SS, Ekblom J, Gudjonsson O, Hagbarth KE, Aquilonius SM. Double blind cross over trial with deprenyl in amyotrophic lateral sclerosis. Journal of Neural Transmission Supplementum 1994;41:237‐41. [PUBMED: 7931231] - PubMed
Kasarskis 1999 {published data only}
    1. A controlled trial of recombinant methionyl human BDNF in ALS. The BDNF Study Group (Phase III). Neurology 1999;52(7):1427‐33. [PUBMED: 10227630] - PubMed
Kaufmann 2008 {published data only}
    1. Kaufmann P, Thompson JL, Levy G, Barsdorf AI, Buchsbaum R, Montes J, et al. Is a phase III trial of coenzyme Q10 (CoQ10) for ALS justified? Results of a phase II randomized controlled trial of CoQ10 for ALS. Neurology 2008;70(11 Suppl 1):A238, Abstract no: S29.005.
Kodama 2000 {published data only}
    1. Kodama M, Kaji R, Kohara N, Imamura A, Inui K, Kimura J, et al. Double‐blind controlled crossover trial of ultra‐high dose methylcobalamin for amyotrophic lateral sclerosis. Neurology 2000;54(Suppl 3):A255.
Kwiecinski 2001 {published data only}
    1. Kwieciński H, Janik P, Jamrozik Z, Opuchlik A. [The effect of selegiline and vitamin E in the treatment of ALS: an open randomized clinical trial]. Neurologia i Neurochirurgia Polska 2001;35(1 Suppl):101‐6. [PUBMED: 11732275] - PubMed
Lacomblez 1996 {published data only}
    1. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V. Dose‐ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996;347(9013):1425‐31. [PUBMED: 8676624] - PubMed
Lacomblez 1996a {published data only}
    1. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Powe L, Durrleman S, et al. A confirmatory dose‐ranging study of riluzole in ALS. ALS/Riluzole Study Group‐II. Neurology 1996;47(6 Suppl 4):S242‐50. [PUBMED: 8959996] - PubMed
Lacomblez 2004 {published data only}
    1. Lacomblez L, Bensimon G, Douillet P, Doppler V, Salachas F, Meininger V. Xaliproden in amyotrophic lateral sclerosis: early clinical trials. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2004;5(2):99‐106. [PUBMED: 15204011] - PubMed
Lai 1997 {published data only}
    1. Lai EC, Felice KJ, Festoff BW, Gawel MJ, Gelinas DF, Kratz R, et al. Effect of recombinant human insulin‐like growth factor‐I on progression of ALS. A placebo‐controlled study. The North America ALS/IGF‐I Study Group. Neurology 1997;49(6):1621‐30. [PUBMED: 9409357] - PubMed
Lange 1996 {published data only}
    1. Lange DJ, Felice KJ, Festoff BW, Gawel MJ, Gelinas DF, Kratz R, et al. Recombinant human insulin‐like growth factor‐I in ALS: description of a double‐blind, placebo‐controlled study. North American ALS/IGF‐I Study Group. Neurology 1996;47(4 Suppl 2):S94‐5. [PUBMED: 8858058] - PubMed
Lange 1998 {published data only}
    1. Lange DJ, Murphy PL, Diamond B, Appel V, Lai EC, Younger DS, et al. Selegiline is ineffective in a collaborative double‐blind, placebo‐controlled trial for treatment of amyotrophic lateral sclerosis. Archives of Neurology 1998;55(1):93‐6. [PUBMED: 9443715] - PubMed
Lauria 2009 {published data only}
    1. Lauria G, Campanella A, Filippini G, Martini A, Penza P, Maggi L, et al. Erythropoietin in amyotrophic lateral sclerosis: a pilot, randomized, double‐blind, placebo‐controlled study of safety and tolerability. Amyotrophic lateral sclerosis: official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 2009;10(5‐6):410‐5. - PubMed
Lomen‐Hoerth 2007 {published data only}
    1. Lomen‐Hoerth C, Scott S, Ramasubbu J, Vieira F, Olney R K. Double‐blind, placebo controlled safety study of ritonavir and hydroxyurea in patients with ALS. Annals of Neurology 2007;62(Suppl 11):S63, Abstract no: T‐54.
Louwerse 1995 {published data only}
    1. Louwerse ES, Weverling GJ, Bossuyt PM, Meyjes FE, Jong JMB. Randomized double‐blind controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Archives of Neurology 1995;52(6):559‐64. [PUBMED: 7763202] - PubMed
Mazzini 1994 {published data only}
    1. Mazzini L, Testa D, Balzarini C, Mora G. An open‐randomized clinical trial of selegiline in amyotrophic lateral sclerosis. Journal of Neurology 1994;241(4):223‐7. [PUBMED: 8195821] - PubMed
Meininger 2004 {published data only}
    1. Meininger V, Bensimon G, Bradley WR, Brooks B, Douillet P, Eisen AA, et al. Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2004;5(2):107‐17. [PUBMED: 15204012] - PubMed
Meininger 2006 {published data only}
    1. Meininger V, Asselain B, Guillet P, Leigh PN, Ludolph A, Lacomblez L, et al. Pentoxifylline in ALS: a double‐blind, randomized, multicenter, placebo‐controlled trial. Neurology 2006;66(1):88‐92. [PUBMED: 16401852] - PubMed
Meyer 2008 {published data only}
    1. Meyer T, Maier A, Borisow N, Dullinger JS, Splettstösser G, Ohlraun S, et al. Thalidomide causes sinus bradycardia in ALS. Journal of Neurology 2008;255(4):587‐91. - PubMed
Miller 1994 {published data only}
    1. Miller RG, Mendoza M, Graves J, Shepard R, Smith S. Controlled trial of nimodipine in amyotrophic lateral sclerosis. Annals of Neurology 1994;36(2):330‐1.
Miller 1996 {published data only}
    1. Miller RG, Moore D, Young LA, Armon C, Barohn RJ, Bromberg MB, et al. Placebo‐controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group. Neurology 1996;47(6):1383‐8. [PUBMED: 8960715] - PubMed
Miller 1996a {published data only}
    1. Miller RG, Petajan JH, Bryan WW, Armon C, Barohn RJ, Goodpasture JC, et al. A placebo‐controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group. Annals of Neurology 1996;39(2):256‐60. [PUBMED: 8967757] - PubMed
Miller 2001 {published data only}
    1. Miller RG, Moore DH 2nd, Gelinas DF, Dronsky V, Mendoza M, Barohn RJ, et al. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 2001;56(7):843‐8. [PUBMED: 11294919] - PubMed
Miller 2007 {published data only}
    1. Miller R, Bradley W, Cudkowicz M, Hubble J, Meininger V, Mitsumoto H, et al. Phase II/III randomized trial of TCH346 in patients with ALS. Neurology 2007;69(8):776‐84. [PUBMED: 17709710] - PubMed
Mitsumoto 1986 {published data only}
    1. Mitsumoto H, Salgado ED, Negroski D, Hanson MR, Salanga VD, Wilber JF, et al. Amyotrophic lateral sclerosis: effects of acute intravenous and chronic subcutaneous administration of thyrotropin‐releasing hormone in controlled trials. Neurology 1986;36(2):152‐9. [PUBMED: 3080695] - PubMed
Munsat 1992 {published data only}
    1. Munsat TL, Taft J, Jackson IM, Andres PL, Hollander D, Skerry L, et al. Intrathecal thyrotropin‐releasing hormone does not alter the progressive course of ALS: experience with an intrathecal drug delivery system. Neurology 1992;42(5):1049‐53. [PUBMED: 1579228] - PubMed
Murphy 1995 {published data only}
    1. Murphy MF, Felice K, Gawel M, Gelinas D, Kratz R, Lai E, et al. A double blind placebo controlled study of myotrophin (CEP 151) in the treatment of amyotrophic lateral sclerosis. Annals of Neurology 1995;38(2):335.
Nagano 2005 {published data only}
    1. Nagano I, Shiote M, Murakami T, Kamada H, Hamakawa Y, Matsubara E, et al. Beneficial effects of intrathecal IGF‐1 administration in patients with amyotrophic lateral sclerosis. Neurological Research 2005;27(7):768‐72. [PUBMED: 16197815] - PubMed
Nefussy 2010 {published data only}
    1. Nefussy B, Artamonov I, Deutsch V, Naparstek E, Nagler A, Drory VE. Recombinant human granulocyte‐colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study. Amyotrophic Lateral Sclerosis 2010;11(1‐2):187‐193. - PubMed
Norris 1974 {published data only}
    1. Norris FH Jr, Calanchini PR, Fallat RJ, Panchari S, Jewett B. The administration of guanidine in amyotrophic lateral sclerosis. Neurology 1974;24(8):721‐8. [PUBMED: 4858705] - PubMed
Norris 1986 {published data only}
    1. Norris FH, Denys EH, Fallat RJ. Trial of octacosanol in amyotrophic lateral sclerosis. Neurology 1986;36(9):1263‐4. [PUBMED: 3528918] - PubMed
Norris 1993 {published data only}
    1. Norris FH, Tan Y, Fallat RJ, Elias L. Trial of oral physostigmine in amyotrophic lateral sclerosis. Clinical Pharmacology and Therapeutics 1993;54(6):680‐2. [PUBMED: 8275623] - PubMed
Ochs 2000 {published data only}
    1. Ochs G, Penn RD, York M, Giess R, Beck M, Tonn J, et al. A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis [see comment]. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2000;1(3):201‐6. [PUBMED: 11464953] - PubMed
Olarte 1979 {published data only}
    1. Olarte MR, Gersten JC, Zabriskie J, Rowland LP. Transfer factor is ineffective in amyotrophic lateral sclerosis. Annals of Neurology 1979;5(4):385‐8. [PUBMED: 443772] - PubMed
Olarte 1985 {published data only}
    1. Olarte MR, Shafer SQ. Levamisole is ineffective in the treatment of amyotrophic lateral sclerosis. Neurology 1985;35(7):1063‐6. [PUBMED: 4010949] - PubMed
Olson 1978 {published data only}
    1. Olson WH, Simons JA, Halaas GW. Therapeutic trial of tilorone in ALS: lack of benefit in a double‐blind, placebo‐controlled study. Neurology 1978;28(12):1293‐5. [PUBMED: 366454] - PubMed
Palma 2000 {published data only}
    1. Palma V, Brescia Morra V, Polverino M, Santoro L, Caruso G. An open study of riluzole versus riluzole plus gabapentin in amyotrophic lateral sclerosis. Journal of the Peripheral Nervous System 2000;5(1):46‐7.
Pascuzzi 2010 {published data only}
    1. Pascuzzi RM, Shefner J, Chappell AS, Bjerke JS, Tamura R, Chaudhry V, et al. A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis 2010;11(3):266‐271. - PubMed
Piepers 2008 {published and unpublished data}
    1. Piepers S, Jong S, Veldink JH, Tweel I, Pol WL, Groeneveld GJG, et al. A randomized, placebo‐controlled, sequential trial of valproic acid in ALS. Neurology 2008;70(11 Suppl 1):A192.
Piepers 2009 {published data only}
    1. Piepers S, Veldink JH, Jong SW, Tweel I, Pol WL, Uijtendaal EV, et al. Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis. Annals of Neurology 2009;66(2):227‐34. - PubMed
Plaitakis 1988 {published data only}
    1. Plaitakis A, Smith J, Mandeli J, Yahr MD. Pilot trial of branched‐chain aminoacids in amyotrophic lateral sclerosis. Lancet 1988;1(8593):1015‐8. [PUBMED: 2896868] - PubMed
Pontieri 2005 {published data only}
    1. Pontieri FE, Ricci A, Pellicano C, Benincasa D, Buttarelli FR. Minocycline in amyotrophic lateral sclerosis: a pilot study. Neurological Sciences 2005;26(4):285‐7. [PUBMED: 16193258] - PubMed
Rivera 1980 {published data only}
    1. Rivera VM, Grabois M, Deaton W, Breitbach W, Hines M. Modified snake venom in amyotrophic lateral sclerosis ‐ lack of clinical effectiveness. Archives of Neurology 1980;37(4):201‐3. [PUBMED: 7362484] - PubMed
Rosenfeld 2008 {published data only}
    1. Rosenfeld J, King RM, Jackson CE, Bedlack RS, Barohn RJ, Dick A, et al. Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Amyotrophic Lateral Sclerosis 2008;9(5):266‐72. [PUBMED: 18608103] - PMC - PubMed
Ryberg 2003 {published data only}
    1. Ryberg H, Askmark H, Persson LI. A double‐blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched‐chain amino acid levels and clinical parameters. Acta Neurologica Scandinavica 2003;108(1):1‐8. [PUBMED: 12807386] - PubMed
Scelsa 2005 {published data only}
    1. Scelsa SN, MacGowan DJ, Mitsumoto H, Imperato T, LeValley AJ, Liu MH, et al. A pilot, double‐blind, placebo‐controlled trial of indinavir in patients with ALS. Neurology 2005;64(7):1298‐300. [PUBMED: 15824372] - PubMed
Smith 1993 {published data only}
    1. Smith RA, Melmed S, Sherman B, Frane J, Munsat TL, Festoff BW. Recombinant growth hormone treatment of amyotrophic lateral sclerosis. Muscle and Nerve 1993;16(6):624‐33. [PUBMED: 8502260] - PubMed
Smith 1994 {published data only}
    1. Smith SA, Miller RG, Murphy JR, Ringel SP. Treatment of ALS with high dose pulse cyclophosphamide. Journal of the Neurological Sciences 1994;124 Suppl:84‐7. [PUBMED: 7807153] - PubMed
Sorenson 2008 {published data only}
    1. Sorenson EJ, Windbank AJ, Mandrekar JN, Bamlet WR, Appel SH, Armon C, et al. Subcutaneous IGF‐1 is not beneficial in 2‐year ALS trial. Neurology 2008;71(22):1770‐5. [PUBMED: 19029516] - PMC - PubMed
Steele 2007 {published data only}
    1. Steele J, Zutshi D, Bradley WG. Negative results of a phase II study of hyperbaric oxygen therapy for amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis 2007;8(5):274‐5. [PUBMED: 17852024] - PubMed
Stommel 2009 {published data only}
    1. Stommel EW, Cohen JA, Fadul CE, Cogbill CH, Graber DJ, Kingman L, et al. Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial. Amyotrophic Lateral Sclerosis 2009;10(5‐6):393‐404. - PMC - PubMed
Szczudlik 1998 {published data only}
    1. Szczudlik A, Tomik B, Slowik A, Kasprzyk K. [Assessment of the efficacy of treatment with pimozide in patients with amyotrophic lateral sclerosis. Introductory notes]. Neurologia i Neurochirurgia Polska 1998;32(4):821‐9. [PUBMED: 9864711] - PubMed
Tandan 1996 {published data only}
    1. Tandan R, Bromberg MB, Forshew D, Fries TJ, Badger GJ, Carpenter J, et al. A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data. Neurology 1996;47(5):1220‐6. [PUBMED: 8909433] - PubMed
Testa 1989 {published data only}
    1. Testa D, Caraceni T, Fetoni V. Branched‐chain amino acids in the treatment of amyotrophic lateral sclerosis. Journal of Neurology 1989;236(8):445‐7. [PUBMED: 2614487] - PubMed
Testa 1992 {published data only}
    1. Testa D, Caraceni T, Fetoni V, Girotti F. Chronic treatment with L‐threonine in amyotrophic lateral sclerosis: a pilot study. Clinical Neurology and Neurosurgery 1992;94(1):7‐9. [PUBMED: 1353011] - PubMed
Tyler 1979 {published data only}
    1. Tyler HR. Double‐blind study of modified neurotoxin in motor neuron disease. Neurology 1979;29(1):77‐81. [PUBMED: 370685] - PubMed
Yanagisawa 1997 {published data only}
    1. Yanagisawa N, Tashiro K, Tohgi H, Mizuno Y, Kowa H, Kimuma J, et al. Efficacy and safety of riluzole in patients with amyotrophic lateral sclerosis: double‐blind placebo‐controlled study in Japan. Igakuno Ayumi 1997;182:851‐66.
Ziv 1994 {published data only}
    1. Ziv I, Achiron A, Djaldetti R, Abraham M, Melamed E. Can nimodipine affect progression of motor neuron disease? A double‐blind pilot study. Clinical Neuropharmacology 1994;17(5):423‐8. [PUBMED: 9316691] - PubMed

References to studies awaiting assessment

Aggarwal 2010 {published data only}
    1. Aggarwal SP, Zinman L, Simpson E, McKinley J, Jackson KE, Pinto H, et al. Northeast, Canadian Amyotrophic Lateral Sclerosis consortia. Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double‐blind, placebo‐controlled trial. Lancet Neurology 2010;9(5):449‐51. [PUBMED: 20363190] - PMC - PubMed
Cudkowicz 2009 {published data only}
    1. Cudkowicz ME, Andres PL, Macdonald SA, Bedlack RS, Choudry R, Brown RH, Jr, et al. Phase 2 study of sodium phenylbutyrate in ALS. Amyotrophic Lateral Sclerosis 2009;10(2):99‐106. [PUBMED: 18688762] - PubMed
Di Lazzaro V 2009 {published data only}
    1. Lazzaro V, Pilato F, Profice P, Ranieri F, Musumeci G, Florio L, et al. Motor cortex stimulation for ALS: a double blind placebo‐controlled study. Neuroscience Letters 2009;464(1):18‐21. [PUBMED: 19682544] - PubMed
Kaufmann 2009 {published data only}
    1. Kaufmann P, Thompson JL, Levy G, Buchsbaum R, Shefner J, Krivickas LS, et al. QALS study group. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Annals of Neurology 2009;66(2):235‐244. [PUBMED: 19743457] - PMC - PubMed
Meininger 2009 {published data only}
    1. Meininger V, Drory VE, Leigh PN, Ludolph A, Robberecht W, Silani V, et al. Glatiramer acetate has no impact on disease progression in ALS at 40 mg/day: a double‐ blind, randomized, multicentre, placebo‐controlled trial. Amyotrophic Lateral Sclerosis 2009;10(5‐6):378‐83. [PUBMED: 19922128] - PubMed
Parry 2010 {published data only}
    1. Parry GJ, Rodrigues CM, Aranha MM, Hilbert SJ, Davey C, Kelkar P, et al. Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic acid in patients with amyotrophic lateral sclerosis. Clinical Neuropharmacology 2010;33(1):17‐21. [PUBMED: 19935406] - PubMed
Sacca 2009 {published data only}
    1. Sacca F, Quarantelli M, Rinaldi C, Tucci T, Piro R, Carotenuto B, et al. A double‐blind, placebo‐controlled, randomized trial of growth hormone as add‐on therapy to riluzole in patients with amyotrophic lateral sclerosis: preliminary MRS, hormonal, and population analysis. Neurology 2009;72(Suppl 3):A36, Abstract no: P07.164.
Zanette 2008 {published data only}
    1. Zanette G, Forgione A, Manganotti P, Fiaschi A, Tamburin S. The effect of repetitive transcranial magnetic stimulation on motor performance, fatigue and quality of life in amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2008;270(1‐2):18‐22. [PUBMED: 18304580] - PubMed

Additional references

Arimoclomol
    1. Benatar M, Cudkowicz M. Phase II/III Randomized, Placebo‐controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis. http://clinicaltrials.gov/ct2/show/NCT00706147?term=arimoclomol&rank=1 June 24, 2008.
BDNF Study 1999
    1. The BDNF Study Group (Phase III). A controlled trial of recombinant methionyl human BDNF in ALS. Neurology 1999;52(7):1427‐33. [PUBMED: 10227630] - PubMed
Beghi 2000
    1. Beghi E, Chiò A, Inghilleri M, Mazzini L, Micheli A, Mora G, et al. A randomized controlled trial of recombinant interferon beta‐1a in ALS. Italian Amyotrophic Lateral Sclerosis Study Group. Neurology 2000;54(2):469‐74. [PUBMED: 10668716] - PubMed
Benatar 2006
    1. Benatar M, Polak M, Kaplan S, Glass J. Preventing familial amyotrophic lateral sclerosis: is a clinical trial feasible?. Journal of the Neurological Sciences 2006; Vol. 251, issue 1‐2:3‐9. [PUBMED: 17005203] - PubMed
Bensimon 1994
    1. Bensimon G, Lacomblez L, Meninger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole study group. New England Journal of Medicine 1994;330(9):585‐91. [PUBMED: 8302340] - PubMed
Bensimon 2002
    1. Bensimon G, Lacomblez L, Delumeau JC, Bejuit R, Truffinet P, Meninger V, ALS/Riluzole study group II. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. Journal of Neurology 2002;249(5):609‐15. [PUBMED: 12021952] - PubMed
Borasio 1998
    1. Borasio GD, Robberecht W, Leigh PN, Emile J, Guiloff RJ, Jerusalem F, et al. A placebo‐controlled trial of insulin‐like growth factor‐I in amyotrophic lateral sclerosis. European ALS/IGF‐I Study Group. Neurology 1998;51(2):583‐6. [PUBMED: 9710040] - PubMed
Chio 2008
    1. Chiò A, Traynor BJ, Lombardo F, Fimognari M, Calvo A, Ghiglione P, et al. Prevalence of SOD1 mutations in the Italian ALS population. Neurology 2008;70(7):533‐537. [PUBMED: 18268245] - PubMed
CNTF Study 1996
    1. A double‐blind placebo‐controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 1996;46(5):1244‐9. [PUBMED: 8628460] - PubMed
Cudkowicz 1997
    1. Cudkowicz ME, McKenna‐Yasek D, Sapp PE, Chin W, Geller B, Hayden DL, et al. Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Annals of Neurology 1997;41(2):210‐21. [PUBMED: 9029070] - PubMed
Cudkowicz 2003
    1. Cudkowicz ME, Shefner JM, Schoenfeld DA, Brown RH Jr, Johnson H, Qureshi M, et al. A randomized, placebo‐controlled trial of topiramate in amyotrophic lateral sclerosis. Neurology 2003;61(4):456‐64. [PUBMED: 12939417 ] - PubMed
Desnuelle 2001
    1. Desnuelle C, Dib M, Garrel C, Favier A. A double‐blind, placebo‐controlled randomized clinical trial of a‐tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS Riluzole‐Tocopherol Study Group. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2001;2(1):9‐18. [PUBMED: 11465936] - PubMed
Forsgren 1983
    1. Forsgren L, Almay BG, Holmgren G, Walls S. Epidemiology of motor neuron disease in northern Sweden. Acta Neurologica Scandinavica 1983;68(1):20‐9. [PUBMED: 6604389] - PubMed
Groeneveld 2003
    1. Groeneveld GJ, Veldink JH, Tweel I, Kalmijn S, Beijer C, Visser M, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Annals of Neurology 2003;53(4):437‐45. [PUBMED: 12666111] - PubMed
Gurney 1994
    1. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 1994;264(5166):1772‐5. [PUBMED: 8209258] - PubMed
Higgins 2008
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Chichester (UK): John Wiley & Sons, 2008.
ISIS 333611
    1. Miller T, Cudkowicz, M. Safety, Tolerability, and Activity Study of ISIS SOD Rx to Treat Familial Amyotrophic Lateral Sclerosis (ALS) Caused by SOD1 Gene Mutations (SOD‐1). http://clinicaltrials.gov/ct2/show/NCT01041222?term=isis&rank=8 December 30, 2009.
Kwiatkowski 2009
    1. Kwiatkowski TJ Jr, Bosco DA, Leclerc A L, Tamrazian E, Vanderburg CR, Russ C, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009;323(5918):1205‐8. - PubMed
Lacomblez 1996
    1. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meninger V. Dose‐ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis/Riluzole Study Group II. Lancet 1996;347(9013):1425‐31. [PUBMED: 8676624] - PubMed
Lai 1997
    1. Lai EC, Felice KJ, Festoff BW, Gawel MJ, Gelinas DF, Kratz R, et al. Effect of recombinant human insulin‐like growth factor‐I on progression of ALS. A placebo‐controlled study. The North America ALS/IGF‐I Study Group. Neurology 1997;49(6):1621‐30. [PUBMED: 9409357] - PubMed
Lopez‐Vega 1988
    1. López‐Vega JM, Calleja J, Combarros O, Polo JM, Berciano J. Motor neuron disease in Cantabria. Acta Neurologica Scandinavica 1988;77(1):1‐5. [PUBMED: 3354306] - PubMed
Meininger 2004
    1. Meininger V, Bensimon G, Bradley WR, Brooks B, Douillet P, Eisen AA, et al. Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2004;5(2):107‐17. [PUBMED: 15204012] - PubMed
Miller 2001
    1. Miller RG, Moore DH 2nd, Gelinas DF, Dronsky V, Mendoza M, Barohn RJ, et al. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 2001;56(7):843‐8. [PUBMED: 11294919] - PubMed
Norris 1993
    1. Norris F, Shepherd R, Denys E, UK, Mukai E, Elias L, et al. Onset, natural history and outcome in idiopathic adult motor neuron disease. Journal of the Neurological Sciences 1993;118(1):48‐55. [PUBMED: 8229050] - PubMed
Orrell 1997
    1. Orrell RW, Habgood JJ, Gardiner I, King AW, Bowe FA, Hallewell RA, et al. Clinical and functional investigation of 10 missense mutations and a novel frameshift insertion mutation of the gene for copper‐zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis. Neurology 1997;48(3):746‐51. [PUBMED: 9065559] - PubMed
Pyrimethamine
    1. Lange D. SOD1 Inhibition by Pyrimethamine in Familial Amyotrophic Lateral Sclerosis (ALS). http://clinicaltrials.gov/ct2/show/NCT01083667?term=lange+d&rank=5 December 17, 2009.
Shefner 2004
    1. Shefner JM, Cudkowicz ME, Schoenfeld D, Conrad T, Taft J, Chilton M, et al. A clinical trial of creatine in ALS. Neurology 2004;63(9):1656‐61. [PUBMED: 15534251] - PubMed
Valdmanis 2008
    1. Valdmanis PN, Rouleau GA. Genetics of familial amyotrophic lateral sclerosis. Neurology 2008;70(2):144‐52. [PUBMED: 18180444] - PubMed
Van Deerlin 2008
    1. Deerlin VM, Leverenz JB, BekrisLM, BirdTD, Yuan W, Elman LB, et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP‐43 neuropathology: a genetic and histopathological analysis. Lancet Neurology 2008;7(5):409‐16. - PMC - PubMed
Vance 2009
    1. Vance C, Rogelj B, Hortobagyi T, Vos KJ, Nishimura AL, Sreedharan J, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009;323(5918):1208‐11. - PMC - PubMed

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