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

Dystonia Clinical Trial

Official title:

A Placebo-Controlled, Double-Blind, Randomized, Cross Over Pilot Study Of The Efficacy And Tolerability Of Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician's Hand

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02107261
• Other study ID #: GCO 13-1679
• Status: Completed
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: January 27, 2020

Study information

• Verified date: April 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: January 27, 2020
• Est. primary completion date: January 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Dystonia
• Dystonic Disorders

Intervention

Drug:
• incobotulinumtoxin A
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.
• Placebo
matching placebo

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Merz North America, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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	Change in Perceived Stress Scale (PSS)	Patient reported outcomes measured by questionnaires that address adverse events and the impact of quality of life using the perceived stress scale. A 10-item questionnaire, each item scored 0 (never) to 4 (very often), full scale from 0-40, with higher score indicating higher perceived stress. the more often the person perceives stress Change in PSS at week 8 compared to baseline	baseline and at 8 weeks
Secondary	Change in Medical Research Council (MRC) Scale	Motor strength using a dynamometer of the finger/wrist/elbow flexors to document any treatment induced weakness.; Scale from 0-4, higher score indicates poorer health outcomes.	baseline and at 8 weeks
Secondary	Change in Motor Strength Comparison	Motor strength tested using a dynamometer to document any weakness the treatment may produce as compared to the baseline visit and 8 weeks.; Dynamometer (DYN) - is a mechanical device that measures the pounds of force that a muscle exerts, Grip - a device that measures grip strength, and finger flexors digit 2 and 3 (FF d2-3). These measures are the amount of lbs of force exert. The higher number is the highest exerted out of 3 tries.	baseline and at 8 weeks