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Randomized Controlled Trial
. 2021 May;28(5):1548-1556.
doi: 10.1111/ene.14714. Epub 2021 Jan 23.

Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial

Masamitsu Hyodo  1 , Asuka Nagao  1 , Kento Asano  2 , Masahiko Sakaguchi  3 , Kenji Mizoguchi  4 , Koichi Omori  5 , Yasuhiro Tada  6 , Hiromitsu Hatakeyama  7 , Nobuhiko Oridate  7 , Kensei Naito  8 , Yoshihiro Iwata  9 , Hirotaka Shinomiya  10 , Hirotaka Hara  11 , Tetsuji Sanuki  12 , Eiji Yumoto  13
Affiliations
Randomized Controlled Trial

Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial

Masamitsu Hyodo et al. Eur J Neurol. 2021 May.

Abstract

Background and purpose: Botulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high-quality clinical studies have appeared, and BT is used off-label in most countries.

Methods: We performed a multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty-four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4 weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period.

Results: In the adductor SD group, the number of aberrant morae at 4 weeks after injection was reduced by 7.0 ± 2.30 (mean ± SE) in the BT group and 0.2 ± 0.46 in the placebo group (p = 0.0148). The improvement persisted for 12 weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2 weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4 weeks.

Conclusions: Botulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.

Keywords: Voice Handicap Index; aberrant morae; botulinum toxin therapy; placebo-controlled double-blinded clinical trial; spasmodic dysphonia.

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Conflict of interest statement

No author has any competing interest. Allergan supported the clinical trial by providing the investigational drug and placebo. GlaxoSmithKline KK provided pharmacological and safety information on Botox and scientific advice pertaining to the conduct of the study, and applied for BT approval to the PMDA after the trial. However, no author or institution received any financial support from either company, nor were they involved in the data collection, analysis and interpretation, study management, or manuscript preparation.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the trial [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Changes in the number of aberrant morae in ADSD. The number of aberrant morae decreased significantly at 2, 4, and 8 weeks after BT injection. *p < 0.05
FIGURE 3
FIGURE 3
Changes in the number of aberrant morae in ABSD. In one case, the number of aberrant morae decreased after BT injection
FIGURE 4
FIGURE 4
Changes in the number of aberrant morae after repeat BT administrations in ADSD. The number of aberrant morae tended to decrease at 2 and 4 weeks after repeat BT administrations
See this image and copyright information in PMC

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References

    1. Blitzer A, Brin MF, Fahn S, Lovelace RE. Clinical and laboratory characteristics of laryngeal dystonia: a study of 110 cases. Laryngoscope. 1988;98:636‐640. - PubMed
    1. Aronson AE, Bless DM. Spasmodic dysphonia, Clinical Voice Disorders, 4th edn. New York, NY: Thieme Med Publ; 2009:101‐133.
    1. Blitzer A. Spasmodic dystonia and botulinum toxin: experience from the largest treatment series. Eur J Neurol. 2010;17(Suppl 1):28‐30. - PubMed
    1. Patel AB, Bansberg SF, Adler CH, Lott DG, Crujido L. The Mayo Clinic Arizona spasmodic dysphonia experience: a demographic analysis of 718 patients. Ann Otol Rhinol Laryngol. 2015;124:859‐863. - PubMed
    1. Hyodo M, Hisa Y, Nishizawa N, et al. The prevalence and clinical features of spasmodic dysphonia: a review of epidemiological surveys conducted in Japan. Auris Nasus Larynx. 2020;48:179‐184. 10.1016/j.anl.2020.08.013. - DOI - PubMed

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