Effectiveness of Myobloc in Treating Dystonia in Musicians

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Solstice Neurosciences
Information provided by (Responsible Party):
Seth Pullman, Columbia University
ClinicalTrials.gov Identifier:
NCT00208091
First received: September 13, 2005
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

This study uses a computerized method to quantify musical performance with music notation analysis before and after treatment with botulinum toxin type B (Myobloc, Solstice Neurosciences). Myobloc is a purified and diluted form of botulinum toxin used medically to relax unwanted muscle spasms and movements. The aim of the study is to quantify any improvements or changes in performance following treatment.


Condition Intervention Phase
Focal Dystonia
Drug: Botulinum toxin, type B
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Computerized Quantitative Open Label Evaluation of the Efficacy of Myobloc in the Treatment of Focal Dystonia in Musicians

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Pitch [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]
  • Note speed [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]
  • Fatigability [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]
  • Timing [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]
  • Tonal deterioration [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]
  • Loudness/force [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Subjective assessment of improvement by patient on scale of 0-100% [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: April 2003
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Botulinum toxin, type B
Diluted botulinum toxin (500 Units/0.1 ml) is injected to the affected muscle(s) through a hollow core needle using electromyographic guidance. Dosage according to muscle(s) and symptom severity. Injection occurs at first visit only, after neurological evaluation.
Drug: Botulinum toxin, type B
Diluted botulinum toxin (500 Units/0.1 ml) is injected to the affected muscle(s) through a hollow core needle using electromyographic guidance. Dosage according to muscle(s) and symptom severity. Injection occurs at first visit only, after neurological evaluation.
Other Name: Myobloc

  Hide Detailed Description

Detailed Description:

Dystonia represents a group of clinical disorders characterized by various combinations of sustained involuntary muscle contractions, abnormal postures and movements, tremors and pain. Dystonia can occur at rest but is more likely to appear during voluntary activity.

Focal dystonia affects one body area and includes blepharospasm, oromandibular dystonia, spasmodic dysphonia, torticollis, and limb dystonia. Focal dystonia typically presents as task-specific muscle spasms or "occupational cramps" in which learned or repetitive motor tasks (such as writing or playing a musical instrument) trigger muscle spasms and interfere with performance while other actions remain normal. Writer's cramp is the most common form of idiopathic limb dystonia [1-3] where involuntary muscle activity and abnormal postures affect the arms and hands, but virtually any part of the body may be affected, even the lips when playing a woodwind or brass instrument [4]. Patients may develop two focal dystonias but rarely does focal dystonia progress to more generalized forms.

As originally defined by Oppenheim [5], dystonia refers to the slow, sustained, writhing, contorting movements of dystonia musculorum deformans. Dystonic movements, however, are often rapid [6] and this can be a cause for misdiagnosis. Electromyography (EMG) may be helpful in corroborating dystonia, but is not essential for diagnostic purposes. Nerve conduction studies, short and long loop reflexes and analysis of motor units are normal [7, 8]. Ballistic movements, which are normally tri-phasic in pattern with alternating agonist-antagonist bursts, may show disrupted patterns with co-contraction of agonist and antagonist muscles and excessively long EMG bursts in dystonia [3].

Dystonic spasms are intriguing in that they may be suppressed (or triggered) by sensory input such as postural change, tactile stimuli, alternative movements or even thought processes [9]. Studies are revealing that the involuntary muscle spasms may be due, at least in part, to abnormal sensory processing of spindle afferent information [10-12]. This may help explain the nature of these sensory "tricks" as well as why the effect of treatment using botulinum toxin usually outlasts the weakness it creates.

Though the pathophysiology of musicians' dystonia has yet to be determined fully, the motor learning associated with playing a musical instrument probably results in both functional and structural changes in the brain [13]. This plastic reorganization, including the rapid unmasking of existing neural circuitry and the establishment of new connections, is probably fundamental to the accomplishment of skillful playing, but also may result in focal, task-specific dystonia. When musicians get dystonia, their playing abilities can become severely compromised, to the point where they may not be able to perform professionally, and possibly not even teach. While botulinum toxin injections can be highly successful in allowing musicians to perform again, there are no objective methods to evaluate improvement.

Subtle dystonic abnormalities in motor control, therefore, particularly when they involve the arms, are difficult to ascertain with a high level of certainty. There are no truly objective measures of arm dystonia, and this is problematic because arm involvement can present so mildly as to go unnoticed by the examiner [14]. Furthermore, patients may not complain of mild finger or thumb cramping, arm twisting or shoulder elevation that could signify the presence of dystonia.

Clinical rating scales, even those that have been validated, do not detect subtle motor dysfunction or small changes after treatment [15] and certainly cannot determine improvement in musical performance. Metabolic imaging studies using positron emission tomography (PET) studies are emerging as helpful ancillary tests, but these are invasive and expensive. Furthermore, while PET studies have implicated that primary dystonia may be associated with relative hypermetabolism in the putamen [16], there have been conflicting reports [17].

This study tests a novel method devised for quantifying change in musical performance that will be able to directly rate or score changes in musical output. It will be a quantitative, objective computerized evaluation that compares the patients' fine motor skills before and after treatment with Myobloc ®. It will be one of the first quantitative analyses of musical ability of its kind and could significantly impact the way musicians determine the efficacy of botulinum toxin treatment.

REFERENCES

  1. Nutt JG, Muenter MD, Melton LJ, Aronson A, Kurland LT. Epidemiology of dystonia in Rochester, Minnesota. Adv Neurol 1988; 50: 361-5.
  2. Sheehy MP, Marsden CD. Writers' cramp - a focal dystonia. Brain 1982; 105: 461-480.
  3. Cohen LG, Hallett M. Hand cramps: clinical features and electromyographic patterns in a focal dystonia. Neurology 1988; 38: 1005-1012.
  4. Frucht S, Fahn S, Ford B. French horn embouchure dystonia. Mov Disord 1999; 14: 171-3.
  5. Oppenheim H. Uber eine eigenartige Krampfkrankheit des kindlichen und jungendichen Alters (dysbasia lordotica progressiva, dystonia musculorum deformans). Neurologie Centralblatt 1911; 30: 1090-1107.
  6. Fahn S. Concept and classification of dystonia. In Fahn, S, Marsden, CD, Caln, DB, ed. Advances in Neurology: Dystonia 2. New York: Raven Press, 1988: 1-8.
  7. Rothwell JC, Obeso JA, Day BL, Marsden CD. Pathophysiology of dystonias. In Desmedt, JE, ed. Advances in Neurology: Motor Control Mechanisms in Health and Disease. New York: Raven Press, 1983: 851-863.
  8. Marsden CD, Rothwell JC. The physiology of idiopathic dystonia. Can J Neurol Sci 1987; 14: 521-527.
  9. Greene PE, Bressman S. Exteroceptive and interoceptive stimuli in dystonia. Mov Disord 1998; 13: 549-51.
  10. Tempel L, Perlmutter J. Abnormal vibration-induced cerebral blood flow responses in idiopathic dystonia. Brain 1990; 113: 691-707.
  11. Kaji R, Rothwell JC, Katayama M, Tomoko I, Kubori T, Kohara N, Mezaki T, Shibasaki H, Kimura J. Tonic vibration reflex and muscle afferent block in writer's cramp. Ann Neurol 1995; 38: 155-162.
  12. Koelman JHTM, Willemse RB, Bour LJ, Hilgevoord AAJ, Speelman JD, Ongerboer de Visser BW. Soleus H-reflex tests in dystonia. Mov Disord 1995; 10: 44-50.
  13. Pascual-Leone A. The brain that plays music and is changed by it. Ann N Y Acad Sci 2001; 930: 315-29.
  14. Bressman SB, de Leon D, Kramer PL, Ozelius LJ, Brin MF, Greene PE, Fahn S, Breakefield XO, Risch NJ. Dystonia in Ashkenazi Jews: Clinical characterization of a founder mutation. Ann Neurol 1994; 36: 771-777.
  15. Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985; 35: 73-77.
  16. Eidelberg D, Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Przedborski S, Fahn S. The metabolic topography of idiopathic torsion dystonia. Brain 1995; 118: 1473-1484.
  17. Karbe H, Holthoff VA, Rudolf J, Herholz K, Heiss WD. Positron emission tomography demonstrates frontal cortex and basal ganglia hypometabolism in dystonia. Neurology 1992; 42: 1540-1544.
  18. Pullman SL. Limb dystonia: Use of botulinum toxin. In Jankovic, J, Hallett, M, ed. Therapeutic Use of Botulinum Toxin. New York: Marcel Dekker, 1994: 307-321.
  19. Medical Research Council Aids to the Examination of the Peripheral Nervous System; Crown: London, 1976.
  20. 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; 53: 617-24.
  21. Cohen LG, Hallett M, Geller BD, Hochberg F. Treatment of focal dystonias of the hand with botulinum toxin injections. J Neurol Neurosurg Psychiatry 1989; 52: 355-363.
  22. Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment of hand tremors. Mov Disord 1994; 9: 601-9.
  Eligibility

Ages Eligible for Study:   25 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Focal, task-specific dystonia clinically determined to be the result of a high level of musical skill and intensive performance history

Exclusion Criteria:

  • Neurological disorders other than dystonia
  • Patients who are clinically depressed, demented or otherwise unable to perform appropriately or sit through 1 hour of testing
  • Patients who have undergone pallidotomy, thalamotomy or deep brain stimulator implantations
  • Patients who have who recently have taken medications with extrapyramidal or tremorogenic side effects
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00208091

Locations
United States, New York
Neurological Institute, 710 W. 168th Street, NI-1112
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Solstice Neurosciences
Investigators
Principal Investigator: Seth Pullman, MD Columbia University Medical Center, Department of Neurology
  More Information

No publications provided

Responsible Party: Seth Pullman, Professor of Clinical, Department of Neurology, Movement Disorders, Columbia University
ClinicalTrials.gov Identifier: NCT00208091     History of Changes
Other Study ID Numbers: AAAB2808
Study First Received: September 13, 2005
Last Updated: November 20, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Myloboc
Botulinum Toxin Type B
Focal Dystonia
Musicians
Muscle Relaxtants
Motor Impairments
Motor Performance
Tremor
Abnormal Postures

Additional relevant MeSH terms:
Dystonia
Dystonic Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Botulinum Toxins
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014