Omega-3 Fatty Acids in Children and Adolescents With Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

A Comparison of Omega-3 Fatty Acids vs. Placebo in Children and Adolescents With Bipolar Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00252486
• Other study ID #: 00-266
• Status: Completed
• Phase: N/A
• First received: November 9, 2005
• Last updated: June 17, 2013
• Start date: November 2001
• Est. completion date: June 2005

Study information

• Verified date: June 2013
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the hypothesis that flax oil, as an omega-3 fatty acid, will be superior to placebo in the maintenance treatment of bipolar disorder in children and adolescents.

Our primary objective was to determine if flax oil is efficacious in the pediatric bipolar population for reducing symptoms of mania and depression. A secondary objective was to examine fatty acid levels as predictors of treatment response and symptom severity. This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-LNA), safely reduced symptom severity in youth with bipolar disorder.

Description:

Pediatric bipolar disorder is a difficult-to-treat recurrent mental illness characterized by a predominant mood state of irritability, and often mixed, rapid-cycling, and psychotic symptoms. Results of randomized controlled trials of lithium, valproic acid, and antipsychotics for early onset bipolar disorder offer hope of improvement for many, yet also demonstrate need for additional treatment options for those children who do not respond adequately to, or cannot tolerate, a first-line mood stabilizer alone or in combination with an atypical antipsychotic. As popular over-the-counter dietary supplements, omega-3 fatty acids represent an appealing option for treatment in the younger bipolar population as they are likely to be better tolerated and cost less compared with conventional mood stabilizing agents. In addition, they have appeal to parents and adolescents due to their perception as a 'natural' substance and relative lack of systemic side effects. To our knowledge, there are no prospective, randomized, controlled trials of flax oil for the treatment of bipolar disorder or selectively evaluating omega-3 fatty acids in the child and adolescent bipolar population.

Children and adolescents aged 6-17 years with symptomatic Bipolar I or II disorder (n=51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg alpha-linolenic acid per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale (YMRS), Child Depression Rating Scale-Revised (CDRS-R), and Clinical Global Impressions- Bipolar (CGI-BP) ratings using Kaplan-Meier survival analyses. Baseline and end-of-study free fatty acids were measured and examined for change and relevance to effect.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: June 2005
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

• male and female outpatients aged 6-17

• DSM-IV diagnosis of bipolar I or II disorder

• currently symptomatic with a CGI of 3 or greater, Y-MRS of 4 or greater, or CDRS-R of 22 or greater

• have failed stabilization with lithium and valproate combined therapy with therapeutic levels documented or are intolerant to these medications

• ability and willingness to provide assent and informed written consent from at least one parent/ legal guardian

Exclusion Criteria:

• mental retardation (IQ less than 70)

• comorbid autism, pervasive developmental disorder, history of substance abuse or positive toxicology screen, or acute post-traumatic stress disorder

• presence of a serious chronic medical illness

• inability to swallow capsules

• pregnant or sexually active without reliable contraception

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Flax oil
Flax oil and olive oil placebo were analyzed for quality and purity; sufficient bioactivity was confirmed for the flax oil independently at the University of Massachusetts mid-way through the study. Each capsule of omega -3 fatty acid concentrate contained 550 mg of a-linolenic acid (a-LNA) from flax seed oil.A stepped but flexible dose-titration schedule was carried out with doses increased by 1-2 grams at each visit as tolerated, to an attempted total dose of 6 capsules twice per day, as requested by the FDA (up to 6.6 grams of daily a-linolenic acid).

Locations

Country	Name	City	State
United States	University of Rochester	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Rochester	Stanley Medical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (3)

McClellan J, Kowatch R, Findling RL; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):107-25. Erratum in: J Am Acad Child Adolesc Psychiatry. 2007 Jun;46(6):786. — View Citation

Nandagopal JJ, DelBello MP, Kowatch R. Pharmacologic treatment of pediatric bipolar disorder. Child Adolesc Psychiatr Clin N Am. 2009 Apr;18(2):455-69, x. doi: 10.1016/j.chc.2008.11.004. Review. — View Citation

Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry. 2005 Jan;162(1):58-64. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Young Mania Rating Scale (YMRS)		EOW 2,4,6,8,10,12,16	No
Primary	Children's Depression Rating Scale (CDRS-R)		EOW 2,4,6,8,10,12,16	No
Primary	Clinical Global Impression - Bipolar Version (CGI)		EOW 2,4,6,8,10,12,16	No