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Meta-Analysis
. 2012 Apr 18;2012(4):CD003495.
doi: 10.1002/14651858.CD003495.pub3.

Intravenous secretin for autism spectrum disorders (ASD)

Katrina Williams  1 , John A Wray, Danielle M Wheeler
Affiliations
Meta-Analysis

Intravenous secretin for autism spectrum disorders (ASD)

Katrina Williams et al. Cochrane Database Syst Rev. .

Abstract

Background: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence.

Objectives: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005.

Search methods: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies.

Selection criteria: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported.

Data collection and analysis: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms.

Main results: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD.

Authors' conclusions: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

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Conflict of interest statement

Katrina Williams ‐ I gave a talk about treatments for autism at a symposium organised by Janssen‐Cilag Pty Ltd. Janssen‐Cilag had no control over the content of the talk and the speaker's fee was paid to the University that employs me. I have no ongoing relationship with Janssen‐Cilag.

John A Wray ‐ was involved in two trials included within this review (Wray; Levy 2003). Dr Wray has declared he delivered a previous testimony for inclusion of risperidone for children with autism on Australia's Public Medicines Prescription Benefit Scheme. Airfares and accommodation were paid for by Janssen Pharmaceutical.

Danielle M Wheeler ‐ none known.

Figures

1
1
Study inclusion pathway
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Core features of autism, outcome: 1.1 Core features of autism, total scores.
4
4
Forest plot of comparison: 4 ADOS, outcome: 4.1 ADOS.
5
5
Forest plot of comparison: 5 Vineland (communication), outcome: 5.1 Vineland four weeks post treatment.
6
6
Forest plot of comparison: 6 Aberrant Behavior Checklist, outcome: 6.1 Aberrant Behavior Checklist 3‐4 weeks post treatment.
1.1
1.1. Analysis
Comparison 1 Core features of autism, Outcome 1 Core features of autism, total scores.
2.1
2.1. Analysis
Comparison 2 ADOS, Outcome 1 ADOS.
3.1
3.1. Analysis
Comparison 3 Vineland (communication), Outcome 1 Vineland four weeks post treatment.
4.1
4.1. Analysis
Comparison 4 Aberrant Behavior Checklist, Outcome 1 Aberrant Behavior Checklist 3‐4 weeks post treatment.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Carey 2002 {published data only}
    1. Carey T, Ratcliff‐Schaub K, Funk J, Weinle C, Myers M, Jenks J. Double‐blind placebo‐controlled trial of secretin: effects on aberrant behavior in children with autism. Journal of Autism and Developmental Disorders 2002;32(3):161‐7. - PubMed
Chez 2000 {published data only}
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Coniglio 2001 {published data only}
    1. Coniglio S, Lewis J, Lang C, Burns T, Subhani‐Siddique R, Weintraub A, et al. A randomized, double‐blind, placebo‐controlled trial of single‐dose intravenous secretin as treatment for children with autism. Journal of Pediatrics 2001;138(5):649‐55. - PubMed
Corbett 2001 {published data only}
    1. Corbett B, Khan K, Czapansky‐Beilman, Brady N, Dropik P, Zelinsky Goldman D, et al. A double‐blind, placebo‐controlled cross‐over study investigating the effect of porcine secretin in children with autism. Clinical Pediatrics 2001;40(6):327‐31. - PubMed
Dunn‐Geier 2000 {published data only}
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Kern 2002 {published and unpublished data}
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Levy 2003 {published data only}
    1. Levy S, Souders M, Wray J, Jawad A, Gallagher P, Coplan J, et al. Children with autistic spectrum disorders. I:comparison of placebo and single dose of human synthetic secretin. Archives of Disease in Childhood 2003;88(8):731‐6. - PMC - PubMed
Molloy 2002 {published data only}
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NCT00036244 {unpublished data only}
    1. NCT00036244. A phase III, randomised, double blind, placebo‐controlled, multiple dose study to assess the efficacy, safety and tolerability of RG1068 (synthetic human secretin) in children with autism. ClinicalTrials.gov: www.clinicaltrials.gov/ct2/show/NCT00036244 Study completed January 2004 (accessed 17 Nov 2011).
Owley 2001 {published data only}
    1. Owley T, McMahon W, Cook E, Laulhere T, South M, Mays L, et al. Multisite, double‐blind placebo‐controlled trial of porcine secretin in autism. Journal of the American Academy of Child and Adolescent Psychiatry 2001;40(11):1293‐9. - PubMed
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Repligen 2002 {unpublished data only}
    1. Krusch DA. Effects of repeated secretin administration on a subset of children with pervasive developmental disorder [PhD dissertation]. Rochester, NY: University of Rochester, 2004.
    1. Repligen Corporation. Repligen Announces Initiation of Phase 3 Clinical Trials for Secretin in Autism. Press release 14 February 2002.
Roberts 2001 {published data only}
    1. Roberts W, Weaver L, Brian J, Bryson S, Emelianova S, Griffiths A, et al. Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo‐controlled trial. Pediatrics 2001;107(5):e71. - PubMed
Sandler 1999 {published data only}
    1. Sandler A, Sutton K, DeWeese J, Girardi M, Sheppard V, Bodfish J. Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. New England Journal of Medicine 1999;341(24):1801‐6. - PubMed
Sponheim 2002 {published data only}
    1. Sponheim E, Oftedal G, Helverschou S. Multiple doses of secretin in the treatment of autism: a controlled study. Acta Paediatrica 2002;91(5):540‐5. - PubMed
Unis 2002 {published data only}
    1. Unis A, Munson J, Rogers S, Goldson E, Osterling J, Gabriels R, et al. A randomized, double‐blind, placebo‐controlled trial of porcine versus synthetic secretin for reducing symptoms of autism. Journal of the American Academy of Child and Adolescent Psychiatry 2002;41(11):1315‐21. - PubMed
Wray {unpublished data only}
    1. Wray J, Wilkins‐Shurmer A, O'Connor G, Knott H, Bint L, Gilroy A. Lack of communication and behavioural response of children with autism from single dose of intravenous porcine secretin. Unpublished.

References to studies excluded from this review

Honomichl 2002 {published data only}
    1. Honomichl R, Goodlin‐Jones B, Burnham M, Hansen R, Anders T. Secretin and sleep in children with autism. Child Psychiatry and Human Development 2002;33(2):107‐23. - PMC - PubMed
Lightdale 2001 {published data only}
    1. Lightdale J, Hayer C, Duer A, Lind‐White C, Jenkins S, Siegal B, et al. Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single‐blinded, open‐label pilot study. Pediatrics 2001;108(5):e90. - PubMed
Lonsdale 2000 {published data only}
    1. Lonsdale D, Shamberger R. A clinical study of secretin in autism and pervasive developmental delay. Journal of Nutritional and Environmental Medicine 2000;10(4):271‐80.
NCT00036231 {unpublished data only}
    1. NCT00036231. A phase III, randomized, double blind, placebo‐controlled, multiple dose study to assess the efficacy, safety and tolerability of RG1068 (synthetic human secretin) in children with autism and gastrointestinal dysfunction [Study terminated]. ClinicalTrials.gov: www.clinicaltrials.gov/ct2/show/NCT00036231 (accessed 17 Nov 2011).
    1. Repligen Corporation. Phase 3 study for secretin for autism fails to meet dual primary endpoints. Development of secretin for schizophrenia to continue. Press release January 5 2004.
Ratliff‐Schaub 2005 {published data only}
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Williams 2009
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