SGA-induced Metabolic Syndrome in Bipolar Youth

Sponsor

University of Cincinnati (Other)

Overall Status

Completed

CT.gov ID

NCT01858948

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators will test the hypothesis that the adverse effects of second-generation antipsychotics exposure and the beneficial effects of long-chain omega-3 (LCn-3) fatty acids are mediated by opposing effects on the enzyme implicated in the metabolic syndrome and obesity.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Youth Treated With Second-generation Antipsychotics	Drug: Omega Drug: Placebo Drug: Quetiapine fumarate	Phase 3

Detailed Description

This will be a two-phase study design:

Phase I: to prospectively investigate the relationship between baseline LCn-3 fatty acid status and treatment-emergent adverse cardiometabolic events and weight gain in response to acute (6-week) open-label quetiapine in first-episode adolescent manic patients (ages 12-17 years). SGA-naïve acutely manic patients will be treated with open-label quetiapine for 6-weeks. Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg, with subjects in the range of 200-500 mg.

Phase II: Patients from Phase I will be randomized to double-blind adjunctive treatment with LCn-3 fatty acids or placebo for an additional 24 weeks to investigate protective effects on the progression and resolution of adverse cardiometabolic events and weight gain during quetiapine maintenance therapy. They will have 6 visits over a 24-week period.

Study Design

Study Type:

Interventional

Actual Enrollment :

94 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2013

Actual Primary Completion Date :

Apr 1, 2018

Actual Study Completion Date :

Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quitiapine plus Omega Patients will be randomized to EPA+DHA supplements (OmegaRx) for 24 weeks	Drug: Omega Omega-3 supplements Other Names: EPA+DHA supplements (OmegaRx) Drug: Quetiapine fumarate Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg. Other Names: Seroquel
Placebo Comparator: Quetiapine plus Placebo Patients will be randomized to similar in shape an color placebo supplements (corn oil)	Drug: Placebo Similar in shape and color to Omega supplements Other Names: Placebo supplements (corn oil) provided by the Inflammation Research Foundation Drug: Quetiapine fumarate Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg. Other Names: Seroquel

Arm

Intervention/Treatment

Experimental: Quitiapine plus Omega

Patients will be randomized to EPA+DHA supplements (OmegaRx) for 24 weeks

Drug: Omega

Omega-3 supplements

Other Names:

EPA+DHA supplements (OmegaRx)

Drug: Quetiapine fumarate

Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg.

Other Names:

Seroquel

Placebo Comparator: Quetiapine plus Placebo

Patients will be randomized to similar in shape an color placebo supplements (corn oil)

Drug: Placebo

Similar in shape and color to Omega supplements

Other Names:

Placebo supplements (corn oil) provided by the Inflammation Research Foundation

Drug: Quetiapine fumarate

Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg.

Other Names:

Seroquel

Outcome Measures

Primary Outcome Measures

BMI [24 weeks]
Body Mass Index, which is a measure of body fat based on height and weight. Calculated as weight in kilograms divided by height in meters squared (kg/m2)
Fasting Triglycerides [24 weeks]
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.

Secondary Outcome Measures

Mood Symptoms [24 weeks]
Symptom ratings will be obtained using the Young Mania Rating Scale (YMRS)

Other Outcome Measures

SEFCA [24 weeks]
Side Effects Form for Children and Adolescents (SEFCA), which measures the frequency and severity of specific cardiovascular, gastrointestinal, central nervous system, ocular, mouth and nasal, genitourinary, dermatological, and musculoskeletal side effects

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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