Clinical trial NCT03254186: Safety and Efficacy of Propranolol in the Treatment of Tardive Dyskinesia
Official title: Safety and Efficacy of Propranolol in the Treatment of Tardive Dyskinesia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Tardive Dyskinesia
Keywords: Propranolol
Safety
Efficacy
Tardive Dyskinesia treatment
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Atlanta Clinical and Translational Science Institute
First posted: 2017-08-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Tardive dyskinesia (TD) is a disabling, embarrassing and often irreversible iatrogenic movement disorder that can occur in anyone exposed to drugs that block dopamine receptors, including first and second generation antipsychotics and antiemetic agents. There is no way to prevent TD except preventing exposure to the inciting agents and there are no approved symptomatic therapies. Propranolol is an FDA-approved β-blocker with limited data supporting its use as a treatment for TD.

The goal of this study is to determine the efficacy of propranolol in the treatment of TD in a double-blind, cross-over prospective manner. If propranolol is found to be an effective therapy, it will fulfill a great need in the treatment of TD with a medication that is known to be safe and inexpensive.

Detailed description: Tardive dyskinesia (TD) is a disabling, embarrassing and often irreversible iatrogenic movement disorder that can occur in anyone exposed to drugs that block dopamine receptors, including first and second generation antipsychotics and antiemetic agents. There is no way to prevent TD except preventing exposure to the inciting agents and there are no approved symptomatic therapies. Propranolol is an FDA-approved β-blocker with limited data supporting its use as a treatment for TD.

The goal of this study is to determine the efficacy of propranolol in the treatment of TD in a double-blind, cross-over prospective manner. Patients with a diagnosis of TD will be randomized to propranolol or identical placebo. The patients will be treated for eight weeks, complete a one week washout and then crossed over for another eight weeks. Hence, the subjects will be their own controls. Participation in this pilot trial will provide placebo controlled blinded data that will assist in planning a larger phase II trial. If propranolol is found to be an effective therapy, it will fulfill a great need in the treatment of TD with a medication that is known to be safe and inexpensive.

Eligibility criteria: Inclusion Criteria:

* age 18-75 years
* diagnosis of classical TD by a movement disorder expert for at least 6 months with a baseline score of at least 2 on two of the seven items on the AIMS severity scale
* stable on medication (either on or off dopamine blocking agents) for at least six months.

Exclusion Criteria:

* breastfeeding
* pregnant
* unstable psychiatric disease
* history of asthma or COPD
* baseline heart rate less than 60
* history of orthostatic hypertension or its presence at screening
* history of congestive heart failure or unstable angina pectoris
* resting SBP \<100 and DBP \< 60
* AV-block II or III without pacemaker
* history of diabetes mellitus
* previous adverse effects from use of beta-blockers
* current use of a β-blocker and the other following drugs: quinidine, amiodarone, propafenone, digoxin, verapamil, diltiazem, clonidine, and warfarin
* tremor, dystonia, akathisia or other non-tardive movement disorder
* any medical illness that precludes treatment with propranolol.

Primary outcomes:
measure: Change in the Abnormal Involuntary Movement Scale (AIMS) score.
timeFrame: Visit 1, 3 4, 6, 7 (up to 18 weeks)
Secondary outcomes:
measure: Change in the Clinical Global Impression of Severity (CGI-S) score.
timeFrame: Visit 1, 3 4, 6 (up to 18 weeks)
measure: Change in the Clinical Global Impression -Improvement (CGI-I) score.
timeFrame: Visit 3 and 6 (up to 18 weeks)
Other outcomes:
measure: Change in the Short Form-36 question health survey (SF-36v2) score.
timeFrame: Visit 1, 3 4, 6 (up to 18 weeks)
measure: Change in the Craniocervical Dystonia Questionnaire (CDQ-24) score.
timeFrame: Visit 1, 3 4, 6 (up to 18 weeks)
Locations:
Study officials:
affiliation: Emory University
name: Jaime Hatcher-Martin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: