Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2007 by Université de Montréal.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by:
Université de Montréal
ClinicalTrials.gov Identifier:
NCT00621634
First received: February 12, 2008
Last updated: February 21, 2008
Last verified: September 2007
  Purpose

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
Tardive Dyskinesia
Dietary Supplement: Omega-3 fish oil capsules (including DHA)
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia

Resource links provided by NLM:


Further study details as provided by Université de Montréal:

Primary Outcome Measures:
  • Clinical rating scales (AIMS, St.Hans) [ Time Frame: Baseline, Week 2, Week 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Quantitative motor testing (kinematic parameters) [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
  • Monitoring of psychopathology (Neuro-Psychiatric Inventory, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia) [ Time Frame: Baseline, Week 2, Week 14 ] [ Designated as safety issue: Yes ]
  • Erythrocyte membrane phospholipid profile (gas chromatography) [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: Yes ]

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
Experimental: 1
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)

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.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00621634

Contacts
Contact: Pierre J. Blanchet, MD, PhD (514) 890-8123 Pierre.J.Blanchet@umontreal.ca

Locations
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   
Sponsors and Collaborators
Université de Montréal
National Alliance for Research on Schizophrenia and Depression
  More Information

Publications:
Responsible Party: Pierre Blanchet/principal investigator, University of Montreal Hospital Center
ClinicalTrials.gov Identifier: NCT00621634     History of Changes
Other Study ID Numbers: HD06.067
Study First Received: February 12, 2008
Last Updated: February 21, 2008
Health Authority: Canada: Natural Health Products Directorate, Health Canada

Keywords provided by Université de Montréal:
Tardive dyskinesia
Schizophrenia
Essential fatty acids

Additional relevant MeSH terms:
Dyskinesias
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on April 15, 2014