SGA-induced Metabolic Syndrome in Bipolar Youth

Study Overview
=================
Brief Summary
-----------------
The investigators tested the hypothesis that long-chain omega-3 (LCn-3) fatty acid supplementation will attenuate the adverse cardiometabolic effects of second-generation antipsychotics exposure in first-episode adolescent manic patients.

Detailed Description
-----------------
Following acute (6-week) open-label treatment with quetiapine, first-episode adolescent manic patients (ages 10-17 years) were randomized to double-blind adjunctive treatment with long-chain omega-3 (LCn-3) fatty acids or placebo for 24 weeks to investigate protective effects on the of adverse cardiometabolic events and weight gain during quetiapine maintenance therapy. They will have 6 visits over a 24-week period.

Official Title
-----------------
Risk and Protective Factors for SGA-induced Metabolic Syndrome in Bipolar Youth

Conditions
-----------------
Bipolar Youth Treated With Second-generation Antipsychotics

Intervention / Treatment
-----------------
* Drug: Omega
* Drug: Placebo
* Drug: Quetiapine fumarate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: DSM-IV-TR criteria for bipolar disorder, type I, manic or mixed episode Baseline YMRS score > 20 Ages 10-17 years Tanner scale stages III-V No prior exposure to SGA medications Fluent in English Provision of written informed consent by a legal guardian and written assent by the subject Manic or depressive symptoms do not result entirely from acute medical illness or acute intoxication or withdrawal from drugs or alcohol as determined by medical evaluation and rapid symptom resolution If female and of child bearing potential, agrees to use one of the following method of birth control: complete abstinence from sexual intercourse, barrier (diaphragm or condom), or oral/injectable contraceptive. For Phase II, additional Inclusion criteria are Receiving a stable therapeutic dose of quetiapine for a minimum of 1 week (i.e., patients who achieved remission (YMRS total score 7 during Phase I) Not requiring concomitant use of antidepressant or mood-stabilizer medications (see Section C.4.c. Concomitant Medications). Exclusion Criteria: IQ < 70, as determined by The Wechsler Abbreviated Scale of Intelligence Positive pregnancy test (to avoid teratogenesis) A history of major cardiovascular or neurological illness Any lifetime DSM-IV-TR substance use disorder (nicotine dependence is permitted) A lifetime DSM-IV-TR diagnosis of any pervasive developmental disorder Any history of a hematological disorder in themselves or a first-degree relative will be excluded (since omega-3 fatty acids may be associated with anti-thrombotic effects). Similarly, concomitant use of medications with anticoagulant effects (e.g. aspirin) will be prohibited Allergy to fish/seafood; 8) Currently taking omega-3 fatty acid supplements

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine plus Omega<br>Patients will be randomized to EPA+DHA supplements (OmegaRx) at fixed dose of 3.0 g/day (EPA: 2.0 g, DHA: 1.0 g; 5 capsules/d) for 24 weeks. | Drug: Omega<br>* Omega-3 supplements<br>* Other names: EPA+DHA supplements (OmegaRx);Drug: Quetiapine fumarate<br>* Prior to randomization to Omega/placebo, patients were started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg.<br>* Other names: Seroquel;|
| Placebo Comparator: Quetiapine plus Placebo<br>Patients will be randomized to similar in shape an color placebo supplements (corn oil) | Drug: Placebo<br>* Similar in shape and color to Omega supplements<br>* Other names: Placebo supplements (corn oil) provided by the Inflammation Research Foundation;Drug: Quetiapine fumarate<br>* Prior to randomization to Omega/placebo, patients were started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg.<br>* Other names: Seroquel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI) | Body Mass Index (BMI) is a measure of body fat calculated as weight in kilograms divided by height in meters squared (kg/m^2). BMI Categories are: Underweight = <18.5; Normal weight = 18.5-24.9; Overweight = 25-29.9; Obesity = BMI of 30 or greater. Greater decreases in BMI are a better outcome. | 24 weeks | 
| Fasting Blood Triglycerides Levels | Triglycerides are the chemical form in which most fat exists in food as well as in the body. They're also present in blood plasma and, in association with cholesterol, form the plasma lipids. Levels are categorized as follows: Normal - Less than 150 milligrams per deciliter (mg/dL); Borderline high - 150 to 199 mg/dL; High - 200 to 499 mg/dL; Very high - 500 mg/dL or above. Greater reductions blood triglyceride levels are a better outcome. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Manic Symptom Severity | Manic symptom ratings will be obtained using the Young Mania Rating Scale (YMRS). The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania: Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania). Greater reductions from baseline indicates a greater improvement in manic symptoms. | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bipolar disorder, Second-generation antipsychotics, Obesity, Cardiometabolic risk