Amlodipine Plus Botulinum Toxin for Focal Dystonia

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00015457
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1

Study Details

Study Description

Brief Summary

Objective: To determine if the calcium channel blockers, amlodipine can augment the effect of botulinum toxin injections in the treatment of focal dystonia.

Study Population: 20 patients with cervical dystonia

Design: Double-bind, placebo-controlled clinical trail.

Outcome measures: For patients: dystonia rating scales (Twistrs, Fahn-Marsden dystonia scale,

NINDS subjective patient rating scale), and hand grip strength. For healthy volunteers:

Amplitude of EDB MEP.

Condition or Disease	Intervention/Treatment	Phase
Focal Dystonia	Drug: Amlodipine plus Botulinum toxin	Phase 2

Detailed Description

Objective: To determine if the calcium channel blocker, amlodipine can augment the effect of botulinum toxin injections in the treatment of focal dystonia.

Study Population: 20 patients with cervical dystonia

Design: Double-bind, placebo-controlled clinical trail.

Outcome measures: dystonia rating scales (TWISTRS)

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Trial of Amlodipine Combined With Botulinum Toxin Injections for Focal Dystonia
• Study Start Date: Apr 1, 2001
• Actual Primary Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cervical dystonia cervical dsytonia patinets	Drug: Amlodipine plus Botulinum toxin

Outcome Measures

Primary Outcome Measures

1. Toronto Western Spasmodic Torticollis Rating Scale (TWSTR) Sum Score [1-2 month maximal rating]

   Rating scale assessing sum of severity of dystonia, disability score and pain scale. Ordinal scale ranging from 0 (least severe) to 30 (maximally severe). Score is maximal response TWSTR rating minus baseline rating.

Secondary Outcome Measures

1. Duration of Response to Botulinum Toxin Injection With Amlodipine and With Placebo [3 months]

   Self reported duration of effect in weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Patients enrolled in Protocol 85-N-0195, Efficacy and Pathophysiology of Botulinum Toxin for Treatment of Involuntary Movement Disorders are eligible for enrollment if they meet the following inclusion and exclusion 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 of 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Anderson RL, Patel BC, Holds JB, Jordan DR. Blepharospasm: past, present, and future. Ophthalmic Plast Reconstr Surg. 1998 Sep;14(5):305-17.
• Jankovic J, Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry. 1990 Aug;53(8):633-9.
• Jankovic J, Schwartz K. Botulinum toxin injections for cervical dystonia. Neurology. 1990 Feb;40(2):277-80.

• Responsible Party: Barbara Karp, M.D., MD, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00015457
• Other Study ID Numbers: 010147; 01-N-0147
• First Posted: Apr 19, 2001
• Last Update Posted: Apr 1, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Barbara Karp, M.D., MD, National Institutes of Health Clinical Center (CC): Writer's Cramp; Calcium Channel Antagonists; Torticollis; Chemodenervation
• Additional relevant MeSH terms: Dystonia; Dystonic Disorders; Amlodipine; Botulinum Toxins

Study Results

Participant Flow

Recruitment Details	Patients recruited from a medical clinic providing botulinum toxin treatment for cervical dystonia. Patients recruited between 6/21/01 and 10/19/06
Pre-assignment Detail	Patients were excluded if response to previous btx injections were not stable, serious medical conditions, pregnancy, abnormal medical screening

Arm/Group Title	Amlodipine Then Placebo	Placebo Then Amlodipine
Arm/Group Description	Patients with cervical dystonia receiving botulinum toxin injections plus Amlodipine during the first period and botulinum toxin injections plus Placebo during the second period.	Patients with cervical dystonia receiving botulinum toxin injections plus Placebo during the first period and botulinum toxin injections plus Amlodipine during the second period.
Period Title: First Intervention
STARTED	8	8
COMPLETED	8	5
NOT COMPLETED	0	3
Period Title: First Intervention
STARTED	8	5
COMPLETED	7	5
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Cervical Dystonia
Arm/Group Description	All participants enrolled in study
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 93.8%
>=65 years	1 6.3%
Sex: Female, Male (Count of Participants)
Female	13 81.3%
Male	3 18.8%

Outcome Measures

1. Primary Outcome

Title	Toronto Western Spasmodic Torticollis Rating Scale (TWSTR) Sum Score
Description	Rating scale assessing sum of severity of dystonia, disability score and pain scale. Ordinal scale ranging from 0 (least severe) to 30 (maximally severe). Score is maximal response TWSTR rating minus baseline rating.
Time Frame	1-2 month maximal rating

Outcome Measure Data

Analysis Population Description

Total enrolled less withdrawals from study. One participant completed the study but did not yield analyzeable data

Arm/Group Title	Amlodipine	Placebo
Arm/Group Description	Patients receiving Amlodipine plus botulinum toxin injections during either period.	Patients receiving Placebo plus botulinum toxin injections during either period.
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	-6.00 (10.23)	-3.23 (6.06)

2. Secondary Outcome

Title	Duration of Response to Botulinum Toxin Injection With Amlodipine and With Placebo
Description	Self reported duration of effect in weeks.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Total enrolled less withdrawals. Less one participant who completed the study but who did not yield analyzeable data.

Arm/Group Title	Amlodipine	Placebo
Arm/Group Description	Patients receiving Amlodipine plus botulinum toxin injections during either period.	Patients receiving Placebo plus botulinum toxin injections during either period.
Measure Participants	11	11
Median (Full Range) [weeks]	6	5.5

Adverse Events

Arm/Group Title	Amlodipine		Placebo
Arm/Group Description	Patients receiving Amlodipine plus botulinum toxin injections during either period.		Patients receiving Placebo plus botulinum toxin injections during either period.
All Cause Mortality
	Amlodipine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Amlodipine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Amlodipine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)		2/16 (12.5%)
Blood and lymphatic system disorders
hypereosinophila	1/16 (6.3%)	1	0/16 (0%)	0
General disorders
dysphagia	0/16 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
swelling	1/16 (6.3%)	1	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.