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Sponsors and Collaborators: |
University of Montreal National Alliance for Research on Schizophrenia and Depression |
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Information provided by: | University of Montreal |
ClinicalTrials.gov Identifier: | NCT00621634 |
Tardive dyskinesia (TD) is a well-known complication of antipsychotic drug therapy in individuals treated for mental disorders such as schizophrenia. It typically consists of purposeless, involuntary movements involving the mouth area or the trunk and limb muscles, occurring within months or years of drug use. The annual incidence of TD in the population treated with antipsychotic drugs is between 1-5%, but the risk is 5-fold greater in older individuals.
Once triggered, TD is often irreversible and untreatable. Its cause is unknown, but an imbalance between chaotic mechanisms triggered by the drugs and natural protective factors fighting against these may provide an explanation. One way to activate this protective response is to supplement the diet with high doses of essential fatty acids of the omega-3 class, which constitute a critical component of nerve cell membranes. Using this strategy, one research team showed a 50% reduction in the severity of TD-like movements in mice treated with docosahexaenoic acid (DHA). We hypothesize that DHA supplements can do the same in patients living with schizophrenia displaying TD movements. Forty (40) subjects between 30-75 years of age will be recruited. The participants will be randomized and equally distributed in two groups to take either DHA capsules (3 grams a day) or matching placebo for 12 weeks, after providing informed consent, and TD will be measured with a magnetic tracker system and clinical scales. The finding of a beneficial effect with DHA against TD would improve the quality of life for thousands of patients under long-term antipsychotic drug treatment.
Condition | Intervention | Phase |
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Tardive Dyskinesia |
Dietary Supplement: Omega-3 fish oil capsules (including DHA) Dietary Supplement: Placebo |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia |
Estimated Enrollment: | 40 |
Study Start Date: | February 2008 |
Estimated Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Active treatment with omega-3 fish oil capsules (1 g each capsule, 50% DHA), 6 capsules each day for 12 weeks
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Dietary Supplement: Omega-3 fish oil capsules (including DHA)
Fish oil capsules of 1000 mg ea., including DHA 460-540 mg/capsule 2 capsules TID daily at mealtime for 12 consecutive weeks
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2: Placebo Comparator
Matching placebo treatment
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Dietary Supplement: Placebo
Corn/Soybean (1:1) placebo 1000 mg capsules 2 capsules TID daily at mealtime for 12 consecutive weeks
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Background
Tardive dyskinesia (TD) is a well-known complication of antipsychotic drug (APD) therapy in individuals treated for mental disorders such as schizophrenia. It typically consists of purposeless, involuntary movements involving the oro-facial area, trunk, and/or limb muscles, occurring within months or years of APD use. Twisting and protruding movements of the tongue, lip smacking and puckering, and chewing movements, are often observed. Oral dyskinesia may cause pain, traumatic lesions, tooth wear, impaired retention of prosthetic devices, chewing difficulty, dysphagia, speech impairment, as well as social embarrassment. The annual incidence of TD in the population treated with these drugs is between 1-5%, but the risk in older individuals is 5-fold greater. The second-generation ("atypical") APDs have substantially reduced the short-term risk of TD, but the annual incidence of TD in older individuals taking these drugs remains comparable to that of younger adults treated with first-generation APDs. The cause of TD is unknown. Since all APDs are blockers of dopamine D2 receptors in the brain, researchers hypothesized that these receptors (or their signaling pathways) become supersensitive in such a way to promote TD. APDs also modulate the expression of a number of brain factors belonging to the nuclear receptor family, including Retinoid X Receptors (RXR) and Nur77, which are overexpressed following chronic APD treatment. These factors, seemingly mounting an adaptive response to fend off adverse drug reactions such as TD, may become incompetent or insufficient over time in those individuals developing TD. One way to activate this response is to supplement the diet with high doses of essential fatty acids of the omega-3 class, which constitute a critical component of nerve cell membranes and modulate a variety of brain receptors. Once triggered, TD is often irreversible and untreatable. However, one team recently showed a 50% reduction in the severity of TD-like movements in mice treated with docosahexaenoic acid (DHA).
Hypothesis
Since there is an apparent close relationship between retinoid receptors and dopamine systems in the human brain and DHA is a RXR agonist, our working hypothesis is that DHA will reduce TD intensity in patients living with schizophrenia by increasing the transcriptional activity along these pathways.
Objective
To evaluate the clinical impact of DHA on the intensity of TD in humans.
Study design
Forty (40) subjects between 30-75 years of age will be recruited. The participants will be randomized and equally distributed in parallel groups to take either DHA (3 grams a day) or matching placebo capsules for 12 weeks, after providing informed consent. The study will use questionnaires, venous blood sampling, as well as clinical scales, to monitor the psychiatric condition, the lipid profile, and TD intensity at the beginning and end of the study.
Brief and simple tasks will also be completed with a motion analysis system using magnetic sensors in order to measure body movements and TD with accuracy.
Outcome
The finding of a beneficial effect with DHA against TD would improve the quality of life for thousands of patients under long-term APD treatment.
Ages Eligible for Study: | 30 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Pierre J. Blanchet, MD, PhD | (514) 890-8123 | Pierre.J.Blanchet@umontreal.ca |
Canada, Quebec | |
Louis-H.-Lafontaine Hospital | Recruiting |
Montreal, Quebec, Canada, H1N 3M5 | |
Contact: Emmanuel Stip, MD (514) 251-4015 ext 3396 emmanuel.stip@umontreal.ca | |
Notre-Dame Hospital/CHU Montreal | Recruiting |
Montreal, Quebec, Canada, H2L 4M1 | |
Contact: Pierre J. Blanchet, MD, PhD (514) 890-8123 Pierre.J.Blanchet@umontreal.ca |
Responsible Party: | University of Montreal Hospital Center ( Pierre Blanchet/principal investigator ) |
Study ID Numbers: | HD06.067 |
Study First Received: | February 12, 2008 |
Last Updated: | February 21, 2008 |
ClinicalTrials.gov Identifier: | NCT00621634 History of Changes |
Health Authority: | Canada: Natural Health Products Directorate, Health Canada |
Tardive dyskinesia Schizophrenia Essential fatty acids |
Schizophrenia Signs and Symptoms Movement Disorders Neurologic Manifestations |
Central Nervous System Diseases Oral Facial Dyskinesia Dyskinesias Tardive Dyskinesia |
Signs and Symptoms Movement Disorders Nervous System Diseases |
Neurologic Manifestations Central Nervous System Diseases Dyskinesias |