Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician's Hand

NCT02107261 | Completed Phase 2 Results

• 1 other identifier: GCO 13-1679
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

The investigational drug being studied in this protocol is Incobotulinumtoxin A (Xeomin®). Botulinum toxin (BoNT) prevents the release of the acetylcholine from peripheral nerves, inhibiting muscle contractions. BoNT is effective in relaxing overactive muscles. In musician's dystonia, the ability to reduce abnormally overactive muscles in the hand can be critical for the musical professional to continue his or her career. With the use of EMG/electrical stimulation and/or ultrasound guidance, the injector can precisely localize the individual muscles that are affected in this condition with great accuracy. Prior studies have shown that BoNT injections produce beneficial effects in forearm muscles, and less effect in shoulder or proximal arm muscles. Possible risks in treating patients with BoNT include excessive weakness of the injected muscles. The drug may also affect non-targeted muscles. However these risks will be minimized during the screening period by carefully targeting the affected muscles and by administering low doses of BoNT. Small booster doses may be given at follow up visit (2, 4, 14 and 16-weeks after the primary injection date) if the initial injection was insufficient to produce sufficient efficacy in relief of the focal dystonia and did not produce excess weakness of the targeted muscle.

Conditions

Dystonia

Keywords

Musician's Dystonia

Outcome Measures

Primary Outcomes (6)

• Physician Global Perception of Change - Blinded Rater 1

  The principal outcome measure was improvement in musical performance, measured by blinded rater, using physician global perception of change at post treatment compared to at 8 weeks. Categories are very much improved, much improved, minimal improved, no change, and minimal worse.

  at visit 4 (week 8)

• Physician Global Perception of Change - Blinded Rater 2

  The principal outcome measure was improvement in musical performance, measured by blinded rater, using physician global perception of change at post treatment compared to at 8 weeks. Categories are very much improved, much improved, minimal improved, no change, and minimal worse.

  at visit 4 (week 8)

• Rating of Overall Musical Performance - Blinded Rater 1

  Rating of overall musical performance based on comparison to baseline video at week 8. Rating from +3, very much improved to -3, very much worse. Higher score indicates more improvement.

  baseline and at 8 weeks

• Rating of Overall Musical Performance - Blinded Rater 2

  Rating of overall musical performance based on comparison to baseline video at week 8. Best Overall Musical Performance on 7 point scale from +3 Very much improved to -3 Very much worse. Higher score indicates more improvement.

  baseline and week 8

• Quantitative MIDI Analysis Comparison

  The principal outcome measure will be improvement in musical performance, measured by self-rated questionnaire, quantitative Musical Instrument Digital Interface (MIDI) analysis and blinded high speed video analysis post treatment compared to baseline and 24 weeks.

  baseline at 24 weeks

• Blinded High Speed Video Analysis Comparison

  The principal outcome measure will be improvement in musical performance, measured by self-rated questionnaire, quantitative MIDI analysis and blinded high speed video analysis post treatment compared to baseline and 24 weeks.

  baseline and at 24 weeks

Secondary Outcomes (3)

• Change in Perceived Stress Scale (PSS)

  baseline and at 8 weeks

• Change in Medical Research Council (MRC) Scale

  baseline and at 8 weeks

• Change in Motor Strength Comparison

  baseline and at 8 weeks

Study Arms (2)

Placebo Then Botulinum Toxin

ACTIVE COMPARATOR

Placebo dose first does then boosters at week 2 and week 4 then 4 weeks washout, then Incobotulinumtoxin A first dose, with boosters at 2 week and week 4.

Drug: incobotulinumtoxin A; Drug: Placebo

Incobotulinumtoxin A Then Placebo

ACTIVE COMPARATOR

Incobotulinumtoxin A dose first does then boosters at week 2 and week 4 then 4 weeks washout, then Placebo first dose, with boosters at 2 week and week 4.

Drug: incobotulinumtoxin A; Drug: Placebo

Interventions

incobotulinumtoxin A DRUG

Incobotulinumtoxin A is being used on average doses between 10U and 30 Units per subject, but at no time will any subject receive over 100 Units. Each study visit, the assessing physician will select the muscles and the amounts of medication to be injected.

Also known as: Xeomin

Incobotulinumtoxin A Then Placebo; Placebo Then Botulinum Toxin

Placebo DRUG

matching placebo

Incobotulinumtoxin A Then Placebo; Placebo Then Botulinum Toxin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with focal task-specific dystonia of one or both hands, selectively triggered by performance on a musical instrument.
• Patients must have been evaluated by Dr. Frucht at the Movement Disorders Division of Mount Sinai Medical Center as part of their clinical care.
• Patients whose performance on an instrument is directly linked to their occupation.
• Patients must be between the ages of 18 and 80.
• Impairment in musical performance must be visible and demonstrable.

You may not qualify if:

• Patients whose dystonia is not severe enough to interfere with musical performance in the opinion of a skilled examiner.
• Patients with unstable medical conditions or psychiatric conditions.
• Patients with a medical condition that precludes them from receiving BoNT injections.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Merz North America, Inc.: collaborator

Study Sites (2)

NYU Langone Health

New York, New York, 10017, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (13)

• Jankovic J, Ashoori A. Movement disorders in musicians. Mov Disord. 2008 Oct 30;23(14):1957-65. doi: 10.1002/mds.22255.

  PMID: 18785647 BACKGROUND

• Pullman SL, Hristova AH. Musician's dystonia. Neurology. 2005 Jan 25;64(2):186-7. doi: 10.1212/01.WNL.0000157497.08500.c1. No abstract available.

  PMID: 15668411 BACKGROUND

• Altenmuller E. Focal dystonia: advances in brain imaging and understanding of fine motor control in musicians. Hand Clin. 2003 Aug;19(3):523-38, xi. doi: 10.1016/s0749-0712(03)00043-x.

  PMID: 12945651 BACKGROUND

• Frucht SJ, Fahn S, Greene PE, O'Brien C, Gelb M, Truong DD, Welsh J, Factor S, Ford B. The natural history of embouchure dystonia. Mov Disord. 2001 Sep;16(5):899-906. doi: 10.1002/mds.1167.

  PMID: 11746620 BACKGROUND

• Elbert T, Pantev C, Wienbruch C, Rockstroh B, Taub E. Increased cortical representation of the fingers of the left hand in string players. Science. 1995 Oct 13;270(5234):305-7. doi: 10.1126/science.270.5234.305.

  PMID: 7569982 BACKGROUND

• Munte TF, Altenmuller E, Jancke L. The musician's brain as a model of neuroplasticity. Nat Rev Neurosci. 2002 Jun;3(6):473-8. doi: 10.1038/nrn843.

  PMID: 12042882 BACKGROUND

• Altenmuller E, Baur V, Hofmann A, Lim VK, Jabusch HC. Musician's cramp as manifestation of maladaptive brain plasticity: arguments from instrumental differences. Ann N Y Acad Sci. 2012 Apr;1252:259-65. doi: 10.1111/j.1749-6632.2012.06456.x.

  PMID: 22524368 BACKGROUND

• Schmidt A, Jabusch HC, Altenmuller E, Hagenah J, Bruggemann N, Hedrich K, Saunders-Pullman R, Bressman SB, Kramer PL, Klein C. Dominantly transmitted focal dystonia in families of patients with musician's cramp. Neurology. 2006 Aug 22;67(4):691-3. doi: 10.1212/01.wnl.0000230148.00035.f9.

  PMID: 16924027 BACKGROUND

• Altenmuller E, Jabusch HC. Focal dystonia in musicians: phenomenology, pathophysiology, triggering factors, and treatment. Med Probl Perform Art. 2010 Mar;25(1):3-9.

  PMID: 20795373 BACKGROUND

• Schuele S, Jabusch HC, Lederman RJ, Altenmuller E. Botulinum toxin injections in the treatment of musician's dystonia. Neurology. 2005 Jan 25;64(2):341-3. doi: 10.1212/01.WNL.0000149768.36634.92.

  PMID: 15668436 BACKGROUND

• Pullman SL, Greene P, Fahn S, Pedersen SF. Approach to the treatment of limb disorders with botulinum toxin A. Experience with 187 patients. Arch Neurol. 1996 Jul;53(7):617-24. doi: 10.1001/archneur.1996.00550070055012.

  PMID: 8929169 BACKGROUND

• Peterson DA, Berque P, Jabusch HC, Altenmuller E, Frucht SJ. Rating scales for musician's dystonia: the state of the art. Neurology. 2013 Aug 6;81(6):589-98. doi: 10.1212/WNL.0b013e31829e6f72. Epub 2013 Jul 24.

  PMID: 23884039 BACKGROUND

• Chang FC, Frucht SJ. Motor and Sensory Dysfunction in Musician's Dystonia. Curr Neuropharmacol. 2013 Jan;11(1):41-7. doi: 10.2174/157015913804999531.

  PMID: 23814536 BACKGROUND

MeSH Terms

Conditions

Dystonia; Dystonia, Focal, Task-Specific

Interventions

incobotulinumtoxinA

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: David Simpson, M.D.
• Organization: Icahn School of Medicine at Mount Sinai

david.simpson@mssm.edu

2122418748

Study Officials

• Steven Frucht, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• David M Simpson, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 26, 2014
• First Posted: April 8, 2014
• Study Start: March 1, 2014
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: May 11, 2023
• Results First Posted: May 11, 2023

Record last verified: 2023-04

Locations

US (2)