Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia
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|ClinicalTrials.gov Identifier: NCT00621634|
Recruitment Status : Unknown
Verified September 2007 by Université de Montréal.
Recruitment status was: Recruiting
First Posted : February 22, 2008
Last Update Posted : February 22, 2008
|Condition or disease||Intervention/treatment||Phase|
|Tardive Dyskinesia||Dietary Supplement: Omega-3 fish oil capsules (including DHA) Dietary Supplement: Placebo||Phase 2|
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).
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.
To evaluate the clinical impact of DHA on the intensity of TD in humans.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia|
|Study Start Date :||February 2008|
|Estimated Primary Completion Date :||June 2011|
Active treatment with omega-3 fish oil capsules (1 g each capsule, 50% DHA), 6 capsules each day for 12 weeks
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
Other Name: 0355EEPB1000CT (Ocean Nutrition Canada)
Placebo Comparator: 2
Matching placebo treatment
Dietary Supplement: Placebo
Corn/Soybean (1:1) placebo 1000 mg capsules 2 capsules TID daily at mealtime for 12 consecutive weeks
Other Name: Placebo1000 (Ocean Nutrition Canada)
- Clinical rating scales (AIMS, St.Hans) [ Time Frame: Baseline, Week 2, Week 14 ]
- Quantitative motor testing (kinematic parameters) [ Time Frame: Baseline, Week 14 ]
- Monitoring of psychopathology (Neuro-Psychiatric Inventory, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia) [ Time Frame: Baseline, Week 2, Week 14 ]
- Erythrocyte membrane phospholipid profile (gas chromatography) [ Time Frame: Baseline, Week 14 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00621634
|Contact: Pierre J. Blanchet, MD, PhD||(514) 890-8123||Pierre.J.Blanchet@umontreal.ca|
|Montreal, Quebec, Canada, H1N 3M5|
|Contact: Emmanuel Stip, MD (514) 251-4015 ext 3396 email@example.com|
|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|