- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00621634
Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia
Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Pierre J. Blanchet, MD, PhD
- Phone Number: (514) 890-8123
- Email: Pierre.J.Blanchet@umontreal.ca
Study Locations
-
-
Quebec
-
Montreal, Quebec, Canada, H1N 3M5
- Recruiting
- Louis-H.-Lafontaine Hospital
-
Contact:
- Emmanuel Stip, MD
- Phone Number: 3396 (514) 251-4015
- Email: emmanuel.stip@umontreal.ca
-
Montreal, Quebec, Canada, H2L 4M1
- Recruiting
- Notre-Dame Hospital/CHU Montreal
-
Contact:
- Pierre J. Blanchet, MD, PhD
- Phone Number: (514) 890-8123
- Email: Pierre.J.Blanchet@umontreal.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- chronic schizophrenia patients under long-term antipsychotic drug treatment, stable for at least 3 months before study entry;
- presence of tardive dyskinesia following Schooler-Kane research criteria (mild intensity (2/4 points) in at least two body segments, or moderate intensity (3∕4 points) for at least one body segment);
- patients capable to understand the goals and procedures of the study, and to provide informed consent;
- women of childbearing age will be requested to use an effective contraceptive method throughout the study.
Exclusion Criteria:
- subjects with medical conditions susceptible to significantly increase the risk of adverse effects, or to interfere with the conduct of the study; in particular, those with a history of coronary artery disease, pancreatitis, diabetes, coagulation disorders, or hemorrhagic conditions;
- those regularly taking aspirin, anticoagulants, or oral lipid-lowering agents;
- those with fasting baseline triglyceride values >4.0 mmol/L, or with cholesterol values >8 mmol/L ;
- those intolerant or allergic to fish, seafood, or any other substance contained in the study medication or matching placebo;
- those who have abused illegal street drugs during the past year;
- those unlikely to comply with the study requirements;
- those who consume natural health products of marine or vegetable source, containing omega-3 essential fatty acids;
- women who are pregnant or breastfeeding.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 2
Matching placebo treatment
|
Corn/Soybean (1:1) placebo 1000 mg capsules 2 capsules TID daily at mealtime for 12 consecutive weeks
Other Names:
|
Experimental: 1
Active treatment with omega-3 fish oil capsules (1 g each capsule, 50% DHA), 6 capsules each day for 12 weeks
|
Fish oil capsules of 1000 mg ea., including DHA 460-540 mg/capsule 2 capsules TID daily at mealtime for 12 consecutive weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Clinical rating scales (AIMS, St.Hans)
Time Frame: Baseline, Week 2, Week 14
|
Baseline, Week 2, Week 14
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Quantitative motor testing (kinematic parameters)
Time Frame: Baseline, Week 14
|
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
|
Baseline, Week 2, Week 14
|
Erythrocyte membrane phospholipid profile (gas chromatography)
Time Frame: Baseline, Week 14
|
Baseline, Week 14
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Ethier I, Kagechika H, Shudo K, Rouillard C, Levesque D. Docosahexaenoic acid reduces haloperidol-induced dyskinesias in mice: involvement of Nur77 and retinoid receptors. Biol Psychiatry. 2004 Oct 1;56(7):522-6. doi: 10.1016/j.biopsych.2004.06.036.
- Beaudry G, Langlois MC, Weppe I, Rouillard C, Levesque D. Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain. J Neurochem. 2000 Oct;75(4):1694-702. doi: 10.1046/j.1471-4159.2000.0751694.x.
- Langlois MC, Beaudry G, Zekki H, Rouillard C, Levesque D. Impact of antipsychotic drug administration on the expression of nuclear receptors in the neocortex and striatum of the rat brain. Neuroscience. 2001;106(1):117-28. doi: 10.1016/s0306-4522(01)00248-2.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HD06.067
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.
Clinical Trials on Tardive Dyskinesia
-
Neurocrine BiosciencesCompletedTardive Dyskinesia (TD)United States, Puerto Rico
-
GGZ CentraalUniversity Medical Center Groningen; Maastricht UniversityTerminatedTardive Dyskinesia | Tardive DystoniaNetherlands
-
Synchroneuron Inc.WithdrawnDrug-induced Tardive DyskinesiaUnited States
-
Centre for Addiction and Mental HealthMerck KGaA, Darmstadt, GermanyTerminatedNeuroleptic-induced Tardive DyskinesiaCanada, India
-
Taoyuan Psychiatric Center, Ministry of Health...Department of HealthCompletedNeuroleptic-Induced Tardive DyskinesiaTaiwan
-
Mitsubishi Tanabe Pharma CorporationCompleted
-
Neurocrine BiosciencesCompletedTardive DyskinesiaUnited States
-
Shanghai Mental Health CenterUnknownTardive DyskinesiaChina
-
Neurocrine BiosciencesEvideraUnknownTardive DyskinesiaUnited States
-
Neurocrine BiosciencesCompletedTardive DyskinesiaUnited States, Puerto Rico
Clinical Trials on Omega-3 fish oil capsules (including DHA)
-
University of VirginiaNational Center for Complementary and Integrative Health (NCCIH)CompletedFatty Liver | Non-alcoholic SteatohepatitisUnited States
-
University of CincinnatiCompletedSchizophrenia | Fatty Acid DeficiencyUnited States
-
Medical Center AlkmaarCompleted
-
National Science Council, TaiwanCompletedMajor Depressive DisorderTaiwan
-
Hackensack Meridian HealthTerminated
-
University of Texas Southwestern Medical CenterCompletedSystemic Lupus ErythematosusUnited States
-
Nordic Pharma, USANutrasource Pharmaceutical and Nutraceutical Services, Inc.CompletedHealthy VolunteersCanada
-
Sulaiman AlRajhi CollegesUnknown
-
University of GuadalajaraRecruitingObesity | Chronic InflammationMexico
-
Université de SherbrookeLaval UniversityCompleted