Safety and Efficacy of Propranolol in the Treatment of Tardive Dyskinesia

Emory University

Status and phase: Withdrawn; Phase 3; Phase 2

Conditions: Tardive Dyskinesia

Treatments: Drug: Propranolol Hydrochloride; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT03254186

IRB00096912

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

Propranolol Hydrochloride

Experimental group

Description:

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.

Treatment:

Drug: Propranolol Hydrochloride

Placebo Oral Tablet

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo Oral Tablet