Oral Uridine for Treatment of Bipolar Depression in Adolescents
Condition: Bipolar Disorder
MeSH terms: Depression; Bipolar Disorder
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Uridine
Intervention type(s): Drug
Intervention description(s): Uridine 500 mg by mouth twice per day for 6 weeks
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bipolar Manic Depression