Conditions: Bipolar Disorder Bipolar Depression Manic Depression
Keywords: Adolescent Bipolar Disorder Bipolar Depression Manic Depression Neuroimaging Magnetic Resonance Spectroscopy Uridine Pyrimidines
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 62
Healthy volunteers: yes

Brief summary:
This is a randomized, double-blind, placebo-controlled study of the investigational drug uridine as a treatment for depressed adolescents with bipolar disorder (i.e. "bipolar depression"). Participants initially randomized to placebo who complete the 6-week protocol will be offered 6 months of open-label uridine treatment and follow-up. Participants initially randomized to uridine will be offered the open-label treatment as well.

Detailed description:
This is a randomized, double-blind, placebo-controlled study of the investigational drug uridine as a treatment for depressed adolescents with bipolar disorder (i.e. "bipolar depression").

In addition to treatment with the investigational drug versus placebo, the study includes a translational neuroimaging component: magnetic resonance spectroscopy (1H-MRS) brain scans are performed at baseline, and then repeated following 6 weeks of treatment with uridine or placebo. The scans do not use radiation, and are performed on a 3 Tesla MRI system that is approved for clinical use. The scans allow researchers to measure the concentrations of several chemicals in the brain that are believed to be involved in bipolar disorder and depression.

The primary hypothesis is that uridine treatment will be associated with a significant decrease in GLX (i.e. glutamate + glutamine) levels, compared to placebo, in a part of the brain known as the anterior cingulate cortex.

The secondary hypothesis is that decreased depressive symptoms measured with the Children Depression Rating Scale-Revised (CDRS-R) and Montgomery-Asberg Depression Rating Scale (MADRS) will be correlated with reductions in GLX.

All participants who complete the initial 6-week protocol, including two brain scans, will be offered 6 months of open-label treatment with uridine.

Arms:
arm 1: Subjects randomized to this study arm will receive uridine 500 mg twice daily by mouth for 6 weeks. arm 2: Subjects randomized to this arm of the study will receive placebo 500 mg twice daily by mouth for 6 weeks. arm 3: Subjects are not randomized, and do not receive any treatment intervention.

Interventions: intervention 1: Uridine intervention 2: Placebo
Intervention descriptions: intervention 1: Uridine is the active treatment in this clinical trial. intervention 2: Pill placebo is the inactive treatment comparator in this clinical trial.

Protocol document: