Omega 3 Fatty Acid Trial

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00586222

Collaborator

National Institutes of Health (NIH) (NIH)

Enrollment

Location

Arms

37.9

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being done to detect the metabolic changes that Omega 3 fatty acid treatment has on the brain and to find out whether magnetic resonance spectroscopy (MRS) scan can detect metabolic differences between bipolar patients and healthy control participants.

Condition or Disease	Intervention/Treatment	Phase
Omega-3 Fatty Acids Pediatric Bipolar Disorder Adolescent Bipolar Disorder Magnetic Resonance Spectroscopy Imaging	Dietary Supplement: Omega-3 Fatty Acid Other: Placebo	Phase 1

Detailed Description

Bipolar disorder (BP) is a chronic, complex and highly heterogeneous disease that has been unrecognized or misdiagnosed in prepubertal children and adolescents. It is one of the most disabling forms of childhood psychopathology and carries a striking human and economic cost. A high percentage of children and adolescents with BP respond very poorly to existing treatments. There is a significant need for studies identifying the developmentally sensitive targets for novel therapeutic compounds for this truly disabling illness. A growing range of novel therapeutic options for the treatment of BP are under investigation. Highly unsaturated fatty acids of the omega-3 fatty acids are among the novel therapeutic compounds considered in the treatment of adult patients with BP. However, the mood-stabilizing efficacy and the neurometabolic effects of this naturally occurring dietary components have not been examined in pediatric patients with BP.

The objective of this study is to identify magnetic resonance spectroscopic characteristics of adolescents with BP before and during a double-blind, placebo controlled combined omega-3 fatty and omega -6 fatty acid trial. We will compare the spectroscopic findings of the BP group with individually matched healthy comparison subjects before and after the omega-3/omega-6 fatty acid treatment. We will identify a well-described cohort of adolescents (age: 12-18) with BP without catatonic features, psychotic features, or other psychiatric comorbidity. Comorbidity with ADHD will be allowed since this might be a separate phenotype for pediatric BP. We will analyze the differences between BP subjects with comorbid ADHD, and BP subjects without ADHD. We will evaluate subjects with a novel magnetic resonance imaging technique, Magnetic Resonance Spectroscopic Imaging (MRSI). We will use a high-field 3T magnet to perform the MRSI acquisition, and apply a tissue volume correction technique to compare absolute metabolite concentrations rather than metabolite ratios. Previous studies found pronounced abnormalities in the frontal lobes, cingulate cortex, thalamus and basal ganglia of patients with BP. Thus, the region of interest in this study will include these anatomical areas with special emphasis given to prefrontal cortex and anterior cingulate cortex.

To our knowledge, this will be the first study examining omega-3 fatty acid induced changes in the developing brain in vivo. The long-term goal of our research group is to identify the developmentally sensitive, trait and state related magnetic resonance spectroscopic markers of pediatric BP. The preliminary data obtained from this application will be used to design a larger scale, follow-up study to examine whether alterations in brain metabolite measures are clinical state or trait markers and to determine the developmental variability in the patterns of metabolic abnormalities. Such knowledge will provide powerful insight into developmentally sensitive targeted pharmacological interventions. Studying bipolar disorder early in its course will be important to minimize potentially confounding factors, such as the effects of long-term medication use and neurodegeneration related to chronic illness course and substance abuse.

Based on the existing literature, we hypothesized that increased myoinositol levels will be detected in the regions of interests of adolescents with BP in comparison to healthy controls.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Supportive Care

Official Title:

Neurometabolic Effects of the Essential Polyunsaturated Fatty Acids in Early-Onset Bipolar Disorder: A Magnetic Resonance Spectroscopy Study

Study Start Date :

Jan 1, 2007

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 2	Other: Placebo placebo pill of the same size, color, and shape as the dietary supplement.
No Intervention: Healthy Comparsions We will compare the BP group with 32 age-, gender-, and handedness-matched healthy adolescents. Subjects who have a first or second degree relative with a psychiatric history will be excluded from the healthy comparison group. Subjects must be safe to undergo MRI scanning as per Mayo MRI safety screening which is explained in detail elsewhere in this protocol. We will exclude the subjects with cardiac pacemakers, metallic clips, other bodily metallic implants and dental braces because of the MRS procedure. Subjects who cannot complete clinical assessments or the MRI scan and subjects who are not fluent in English will be excluded from the study.
Experimental: 1	Dietary Supplement: Omega-3 Fatty Acid 600 mg of eicosapentaenoic acid, 340 g of docosahexanoic acid, and 96 mg gama-linoleic acid for 12 weeks.

Arm

Intervention/Treatment

Placebo Comparator: 2

Other: Placebo

placebo pill of the same size, color, and shape as the dietary supplement.

No Intervention: Healthy Comparsions

We will compare the BP group with 32 age-, gender-, and handedness-matched healthy adolescents. Subjects who have a first or second degree relative with a psychiatric history will be excluded from the healthy comparison group. Subjects must be safe to undergo MRI scanning as per Mayo MRI safety screening which is explained in detail elsewhere in this protocol. We will exclude the subjects with cardiac pacemakers, metallic clips, other bodily metallic implants and dental braces because of the MRS procedure. Subjects who cannot complete clinical assessments or the MRI scan and subjects who are not fluent in English will be excluded from the study.

Experimental: 1

Dietary Supplement: Omega-3 Fatty Acid

600 mg of eicosapentaenoic acid, 340 g of docosahexanoic acid, and 96 mg gama-linoleic acid for 12 weeks.

Outcome Measures

Primary Outcome Measures

Cases will classify as either treatment responders or non. Using dichotomous assessment, logistic regression will assess association of regional mI levels and mood measures taken at baseline, adjusting for important covariates such as age and gender. [at the 12 week point]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

12 to 18 years old
both male and female
all ethnic backgrounds
DSM-IV criteria for Bipolar Disorder without catatonic and psychotic features or other psychiatric comorbidity, except ADHD