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.

Condition	Treatment or Intervention	Phase
Focal Dystonia	Drug: Amlodipine plus Botulinum toxin	Phase II

Botulinum toxin injections are now in widespread use for the treatment of focal dystonias. Although many patients respond to treatment, their response is often suboptimal, both in the degree and duration of benefit. Botulinum toxin works by blocking acetylcholine exocytosis, a process that also requires calcium influx from the extracellular environment. Botulinum toxin type A does not completely prevent neurotransmitter release in poisoned nerve terminals. Calcium channel blockers, by preventing calcium entry into the presynaptic cell, can augment the blockade of acetylcholine release by botulinum toxin type A. This is a double-blind, placebo-controlled, cross-over trial of the calcium channel blocker, amlodipine, in patients with focal dystonia and in normal volunteer to determine if calcium channel blockage can enhance weakness due to and the clinical efficacy of botulinum toxin injections.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

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

Maryland
      National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  010147; 01-N-0147
Record last reviewed:  March 23, 2004
Last Updated:  March 23, 2004
Record first received:  April 18, 2001
ClinicalTrials.gov Identifier:  NCT00015457
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08