Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia

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Brief Title

Efficacy of Docosahexaenoic Acid on Tardive Dyskinesia

Official Title

Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Omega-3 Supplementation With Docosahexaenoic Acid (DHA) on Tardive Dyskinesia

Brief Summary

      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.
    

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Clinical rating scales (AIMS, St.Hans)

Secondary Outcome

 Quantitative motor testing (kinematic parameters)

Condition

Tardive Dyskinesia

Intervention

Omega-3 fish oil capsules (including DHA)

Study Arms / Comparison Groups

 1
Description:  Active treatment with omega-3 fish oil capsules (1 g each capsule, 50% DHA), 6 capsules each day for 12 weeks

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Dietary Supplement

Estimated Enrollment

40

Start Date

February 2008


Primary Completion Date

June 2011

Eligibility 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.
      

Gender

All

Ages

30 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

, (514) 890-8123, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT00621634

Organization ID

HD06.067



Study Sponsor

Université de Montréal

Collaborators

 National Alliance for Research on Schizophrenia and Depression

Study Sponsor

, , 


Verification Date

September 2007