Safety and Efficacy of Propranolol in the Treatment of Tardive Dyskinesia

NCT ID: NCT03254186

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-18
• Study Completion Date: 2019-02-01

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.

Conditions

Tardive Dyskinesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Propranolol Hydrochloride

Two week up-titration to reach a total dose of 20mg per oral four times per day over the first two weeks then will remain on a stable dose for six weeks. The patients will be treated for eight weeks, complete a one week washout and then crossed over to another arm for eight weeks.

Group Type: EXPERIMENTAL

Propranolol Hydrochloride

Intervention Type: DRUG

Propranolol is started 10 mg tablet twice per day per oral, two week up-titration to reach a total dose of 20mg per oral four times per day over the first two weeks, then will remain on a stable dose for six weeks.

Placebo Oral Tablet

Identical placebo. The patients will be treated for eight weeks, complete a one week washout and then crossed over to another arm for eight weeks.

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Identical placebo is started one tablet twice per day per oral, increase over the first two weeks to reach one tablet four times per day, then will remain on this dose for six weeks.

Interventions

Propranolol Hydrochloride

Propranolol is started 10 mg tablet twice per day per oral, two week up-titration to reach a total dose of 20mg per oral four times per day over the first two weeks, then will remain on a stable dose for six weeks.

Intervention Type: DRUG

Placebo Oral Tablet

Identical placebo is started one tablet twice per day per oral, increase over the first two weeks to reach one tablet four times per day, then will remain on this dose for six weeks.

Intervention Type: DRUG

Other Intervention Names

Inderal; Placebo

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Atlanta Clinical and Translational Science Institute

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Jaime Hatcher-Martin

Asstant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jaime Hatcher-Martin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Other Identifiers

IRB00096912

Identifier Type: -

Identifier Source: org_study_id