Protocol Number: 01-N-0147

Title:

Trial of Amlodipine Combined with Botulinum Toxin Injections for Focal Dystonia

Number:

01-N-0147

Summary:

This study will examine whether amlodipine (Norvasc) can improve the effect of botulinum toxin injections for dystonia a movement disorder causing abnormal postures and disrupted movements.

Amlodipine, a drug commonly used to treat high blood pressure and heart disease, prevents calcium from entering cells under certain conditions. Botulinum toxin works by weakening muscles that are overactive in dystonia. It prevents the release of a chemical called acetylcholine from nerve terminals that signal the muscle to contract. The release of acetylcholine also requires that small amounts of calcium enter the cell. This calcium can be blocked by amlodipine. Therefore, the use of the two drugs together may produce more weakness and possibly more benefit than botulinum toxin injection alone.

Patients enrolled in NINDS's protocol 85-N-0195 (Efficacy and Pathophysiology of Botulinum Toxin for Treatment of Involuntary Movement Disorders) who are being treated with botulinum toxin for focal hand dystonia or cervical dystonia may be eligible for this study. Candidates will be screened with blood tests and electrocardiogram (EKG).

Participants will have three injections of botulinum toxin, during which the following will occur:

First injection - Patients' dystonia will be rated and their hand strength tested. They will be randomly assigned to receive either amlodipine or placebo (a look-alike pill with no active ingredient) for 6 months or until the effects of the botulinum toxin injection have worn off and the second injection is required.

Second injection - No amlodipine or placebo will be given with the second injection in order to allow any effects of amlodipine to wear off.

Third injection - Will be given when the effects of the second injection have worn off. At this time, patients who received amlodipine at the time of the first injection will now be given placebo, and vice versa.

Patients will be seen at monthly intervals after the first and third injections to evaluate their response to treatment. At each visit, patients will report any side effects of treatment, their dystonia will be videotaped and rated and their hand strength will be tested. In addition, 2 weeks after the first and third injections, patients will have electromyography (EMG) testing to evaluate how the study medication affects the nerves and release of acetylcholine from the nerve. This test involves inserting a needle into an arm muscle. For part of the study, patients will tense the muscle slightly and maintain tension while the EMG signal is collected. This test may take 1 to 2 hours.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Good general health

Focal hand dystonia or cervical dystonia

Stable response to botulinum toxin demonstrated through a series of at least 3 injections over a period of at least a year

Benefit from the 3 immediately prior btx injections rated as 75% or less or a duration of benefit lasting less than or equal to 2 months

No other medications for dystonia

EXCLUSION CRITERIA:

Cervical dystonia accompanied by dysphagia or dyspnea, either before or with botulinum toxin injection

Present or past cardiac disease, hypertension, arrhythmia or congestive heart failure

Anterocollis or other neck dystonia requiring bilateral anterior neck muscle injections

Use concomitant medications affecting calcium channels or those metabolized by the cytochrome p450 3A4 system including grapefruit juice, St. John's wort, HIV protease inhibitors, cimetidine, antibiotics (macrolides, fluoroquinones, antifungal, rifampin), antidepressants (fluvoxamine, norfluoxetine), barbiturates, anticonvulsants (carbamazepine, phenytoin), oral diabetes agents (pioglitazone, troglitazone), and glucocorticoids

Allergy to amlodipine or related compounds

Pregnany/ nursing

Age less than 18 years of age

Abnormal EKG

Abnormal coagulation profile or liver function tests

Use of anticoagulants

Special Instructions: Currently Not Provided

Keywords:

Writer's Cramp

Calcium Channel Antagonists

Torticollis

Chemodenervation

Recruitment Keywords:

None

Conditions:

Focal Dystonia

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Blepharospasm: past, present, and future

Botulinum toxin injections for cervical dystonia

Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm

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