Clinical trial NCT00841269
Conditions: Bipolar Disorder
Keywords: Bipolar Manic Depression
Sponsor: University of Utah
Start date: 2009-05-01; Completion date: 2013-06-01
Enrollment: 42 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to see if the investigational medication uridine reduces depression symptoms in adolescents with bipolar disorder. Uridine is a naturally occurring chemical that is made by the human liver. Uridine is part of a family of compounds called pyrimidines, and is normally involved in many of the body's processes such as the use of energy by cells. Uridine is considered experimental, because it has not been approved by the U.S. Food and Drug Administration (FDA) to treat bipolar depression in adolescents. The study will use standard methods of assessing adolescent's mood, such as rating scales and questionnaires. In addition, the study will use Magnetic Resonance Imaging Spectroscopy (MRI/MRS) brain scans to see if levels of certain chemicals in the brain change when adolescents are treated with uridine. These scans use a magnet to create images of the brain, and do not expose patients to radiation.

Detailed description:
This is an open-label study of the investigational drug uridine in the treatment of adolescents with depression with bipolar disorder. Uridine has shown positive results in a Phase II study of bipolar disorder in adults (http://clinicaltrials.gov/ct2/show/NCT00322764). This study will enroll 30 depressed adolescent participants who meet DSM-IV-TR criteria for bipolar disorder type I, type II or bipolar disorder not otherwise specified. Participants who are currently taking psychotropic medication(s) will continue on their current regimen, with uridine added as adjunctive therapy. Participants who are untreated will be informed of the alternatives to study participation. This will include informing the parent(s) or guardian(s) that Lithium, Risperdal and Abilify are FDA-approved treatments for adolescent bipolar disorder that would be available to their child in community care.

The study has three objectives: 1) To use Magnetic Resonance Spectroscopy (MRS) brain imaging to measure levels of beta-nucleoside triphosphate (b-NTP) in the anterior cingulate cortex of 30 adolescents with bipolar disorder, before-and-after 6 weeks of treatment with the investigational drug uridine; 2) To measure the antidepressant response to uridine in the 30 participants with the Children's Depression Rating Scale (CDRS); and 3) To acquire structural Magnetic Resonance Imaging (MRI) data in the 30 participants with bipolar disorder and the 30 healthy controls, to establish regionally-specific structure/neurochemical relationships.

Adolescent participants with bipolar disorder will be treated with uridine 500mg twice daily for six weeks. The primary clinical outcome measure is the Children's Depression Rating Scale (CDRS), with response defined as a 30% reduction in CDRS score. In addition to this standardized clinical assessment, participants will undergo magnetic resonance imaging and magnetic resonance spectroscopy (MRI/MRS) brain scans at baseline, and after six weeks of treatment with uridine. This novel approach is designed to explore objectively measurable biomarkers of illness and treatment response in pediatric bipolar disorder. The investigators hypothesize that participants whose depression responds to uridine will demonstrate an increased concentration of beta-nucleoside triphosphate (b-NTP) in the anterior cingulate cortex. This would support the hypothesis that depressive states are associated with abnormalities in brain energy metabolism.

As a neuroimaging comparison group for the participants with bipolar disorder, 30 healthy adolescent controls with no history of psychiatric illness will be recruited for MRI/MRS scanning only. The investigators hypothesize that controls will have higher levels of b-NTP in the anterior cingulate cortex than participants with depression associated with bipolar disorder, further supporting a connection between brain bioenergetics and depression.

Arms: arm 1: Uridine 500 mg by mouth twice daily for 6 weeks arm 2: Healthy comparison participants were seen for baseline and week 6 MRI scans. No treatment was administered to participants enrolled as healthy comparisons.
Interventions: intervention 1: Uridine
Intervention descriptions: intervention 1: Uridine 500 mg by mouth twice per day for 6 weeks

Protocol documents: