Treatment of Tardive Dyskinesia With Galantamine

September 9, 2005 updated by: Caroff, Stanley N., M.D.
Tardive dyskinesia (TD), a form of movement disorder, remains a problem for some patients who received antipsychotic medications. Increasing evidence suggests that TD may result from antipsychotic-induced dysfunction in striatal cholinergic neurons. To test whether cholinesterase inhibitors compensate for diminished cholinergic activity underlying TD, we conducted a 30-week randomized, double-blind, placebo-controlled crossover study of galantamine in 36 patients with TD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND: Tardive dyskinesia (TD) is an infrequent but important complication of treatment with antipsychotic medications. Although newer antipsychotics may be less likely to cause TD, it still occurs among some mentally ill patients previously treated with typical antipsychotics. Although usually mild, TD may be more troublesome in some patients. There is no proven curative or suppressive treatment that is effective in all patients. Suppressive treatment with cholinergic agents derives from a hypothesized balance between dopaminergic and cholinergic neurotransmission in the extrapyramidal system. Although previous trials of cholinergic precursors have been unsuccessful in treating TD, their effect on central cholinergic neurotransmission remains uncertain in view of evidence of damage to striatal cholinergic neurons in patients with TD. In contrast, the recent development of cholinesterase inhibitors that are effective in modifying the central cholinergic deficit in Alzheimer's disease, prompted us to investigate the therapeutic effect of galantamine in patients with TD.

RESEARCH OBJECTIVES: We propose to complete a randomized, double-blind, placebo-controlled crossover trial in 36 patients to test; (1) whether galantamine is pharmacologically active in suppressing TD; (2) whether doses of 8-24 mg/day are sufficient for improvement; (3) whether there are any significant side effects in these patients.

METHODS: Thirty-six patients with abnormal involuntary movements meeting research criteria for TD, who are on stable doses of psychotropic medications, will be randomized to receive galantamine alternating with placebo in addition to their standard medications. After 2 baseline measurements, each patient will undergo 12-week treatment periods of galantamine and placebo with a 4-week washout period between treatments. Patients will be evaluated every 2 weeks throughout the study, using standardized rating scales for TD (AIMS) and other extrapyramidal side effects (SIMPSON, BARNES. During the active treatment period, patients will receive galantamine 4 mg BID for 4 weeks followed by 8 mg BID for 4 weeks, and 12 mg BID for an additional 4 weeks. Placebo-galantamine differences will be examined by repeated measures analysis of covariance for a two-period crossover design.

Study Type

Interventional

Enrollment

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Philadelphia VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical diagnosis of tardive dyskinesia lasting at least 3 months
  • Treatment with antipsychotic drugs at least for 3 months
  • 18 years old or older

Exclusion Criteria:

  • Significant active medical illness
  • Allergy to galantamine
  • Pregnancy
  • Drug or alcohol dependence
  • Necessary use of anticholinergics or vitamin E

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Change in Abnormal Involuntary Movement scale at 3 months.

Secondary Outcome Measures

Outcome Measure
Change in Simpson-Angus and Barnes Akathisia scales at 3 moths.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Caroff, Stanley N., M.D.

Collaborators

Ortho-McNeil Neurologics, Inc.

Investigators

  • Principal Investigator: Stanley N Caroff, MD, Corporal Michael J. Crescenz VA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2002

Study Completion

October 1, 2004

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (ESTIMATE)

September 14, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

September 14, 2005

Last Update Submitted That Met QC Criteria

September 9, 2005

Last Verified

September 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00347

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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