Clinical trial NCT01805440: Uridine Adolescent Bipolar Depression Randomized Controlled Trial
Official title: Placebo-Controlled Study of Uridine for Adolescent Bipolar Depression: a Magnetic Resonance Spectroscopy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bipolar Disorder
Bipolar Depression
Manic Depression
Keywords: Adolescent
Bipolar Disorder
Bipolar Depression
Manic Depression
Neuroimaging
Magnetic Resonance Spectroscopy
Uridine
Pyrimidines
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: The Depressive and Bipolar Disorder Alternative Treatment Foundation
First posted: 2013-03-06
Enrollment: 62
Sex: ALL
Minimum age (years): 13
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria For Bipolar Disorder Participants:

* Participants under 18 years of age must be able to provide assent, and have the permission of a parent or guardian. Participants 18 years of age or older must be able to provide informed consent.
* Participants must be between the ages of 13 and 21 years.
* Participants must meet DSM criteria for Bipolar Disorder (Type I, II, or NOS), with current mood state depressed for at least 2 weeks.
* Participants must have a current Children's Depression Rating Scale-Revised (CDRS-R) score of 45 or greater, and/or a Montgomery/Asberg Depression Rating Scale (MADRS) score of 25 or greater.

Inclusion Criteria For Healthy Comparison Participants:

* Participants under 18 years of age must be able to provide assent, and have the permission of a parent or guardian. Participants 18 years of age or older must be able to provide informed consent.
* Participants must be between the ages of 13 and 21 years.
* Participants must not meet any DSM-IV criteria for a psychiatric illness or substance use disorder

Exclusion Criteria:

* Participants must not meet DSM criteria for a primary psychotic disorder, a developmental disorder or substance use disorder.
* Participants must not be at high risk for suicidal or homicidal actions.
* Participants must not be pregnant or breastfeeding.
* Participants must not have a contraindication to magnetic resonance imaging (e.g. ferromagnetic implant, or claustrophobic anxiety).
* Incarcerated persons are excluded, because this study is not approved for Research Involving Prisoners.

Primary outcomes:
measure: Change in GLX (Glutamate + Glutamine) to Creatine (Cr) Ratio in the Anterior Cingulate Cortex of the Brain, as Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS).
timeFrame: Baseline and 6 weeks
measure: Change in Children's Depression Rating Scale-Revised (CDRS-R) Score.
timeFrame: 6 weeks
Secondary outcomes:
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Douglas Kondo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kondo DG, Sung YH, Hellem TL, Delmastro KK, Jeong EK, Kim N, Shi X, Renshaw PF. Open-label uridine for treatment of depressed adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2011 Apr;21(2):171-5. doi: 10.1089/cap.2010.0054. Epub 2011 Apr 12.