Treatment of Tardive Dyskinesia With Galantamine

NCT ID: NCT00164242

Last Updated: 2005-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2004-10-31

Brief Summary

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.

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.

Conditions

Tardive Dyskinesia

Keywords

Tardive dyskinesia; Galantamine; Cholinesterase inhibitors

Study Design

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

Interventions

Galantamine

Intervention Type: DRUG

Eligibility Criteria

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

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

Sponsors

Ortho-McNeil Neurologics, Inc.

INDUSTRY

Sponsor Role: collaborator

Caroff, Stanley N., M.D.

INDIV

Sponsor Role: lead

Principal Investigators

Stanley N Caroff, MD

Role: PRINCIPAL_INVESTIGATOR

Corporal Michael J. Crescenz VA Medical Center

Locations

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

Caroff SN, Campbell EC, Havey J, Sullivan KA, Mann SC, Gallop R. Treatment of tardive dyskinesia with donepezil: a pilot study. J Clin Psychiatry. 2001 Oct;62(10):772-5. doi: 10.4088/jcp.v62n1004.

Reference Type: BACKGROUND

PMID: 11816865 (View on PubMed)

Caroff SN, Walker P, Campbell C, Lorry A, Petro C, Lynch K, Gallop R. Treatment of tardive dyskinesia with galantamine: a randomized controlled crossover trial. J Clin Psychiatry. 2007 Mar;68(3):410-5. doi: 10.4088/jcp.v68n0309.

Reference Type: DERIVED

PMID: 17388711 (View on PubMed)

Other Identifiers

00347

Identifier Type: -

Identifier Source: secondary_id

00347

Identifier Type: -

Identifier Source: org_study_id