Oral Uridine for Treatment of Bipolar Depression in Adolescents
|ClinicalTrials.gov Identifier: NCT00841269|
Recruitment Status : Completed
First Posted : February 11, 2009
Results First Posted : January 8, 2015
Last Update Posted : March 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Bipolar Disorder||Drug: Uridine||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Oral Administration of Uridine for Treatment of Bipolar Depression in Adolescents: A Magnetic Resonance Spectroscopy Study|
|Study Start Date :||May 2009|
|Actual Primary Completion Date :||June 2013|
|Actual Study Completion Date :||June 2013|
Uridine 500 mg by mouth twice daily for 6 weeks
Uridine 500 mg by mouth twice per day for 6 weeks
No Intervention: Healthy Comparison
Healthy comparison participants were seen for baseline and week 6 MRI scans. No treatment was administered to participants enrolled as healthy comparisons.
- Mean Scores in Children's Depression Rating Scale (CDRS-R), Assessed Before and After 6 Week Uridine Treatment [ Time Frame: 6 weeks ]The CDRS-R is a 17-item scale, with items rated for severity on a 5 point scale for 3 items and on a 7 point scale for 14 items (possible total score from 17 to 113). Ratings are completed by a clinician via interviews with the child or parent. Scores ≥40 are indicative of depression, whereas scores ≤28 is often used to define remission.
- The Primary Neuroimaging Outcome Will be Changes in Beta-NTP to TP (Total Phosphorus) Ratio in the Anterior Cingulate. [ Time Frame: 6 weeks ]
- A Secondary Outcome Measure Includes a Change in Young Mania Rating Scale (YMRS) Score [ Time Frame: 6 weeks ]The Young Mania Rating Scale (YMRS) is an 11-item rating scale that evaluates manic symptoms. Total scores range from 0-60, with higher scores indicating more manic symptoms endorsed by research participants.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00841269
|United States, Utah|
|University of Utah School of Medicine|
|Salt Lake City, Utah, United States, 84108|
|Principal Investigator:||Douglas G Kondo, M.D.||University of Utah|