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Uridine Adolescent Bipolar Depression Randomized Controlled Trial

Primary Purpose

Bipolar Disorder, Bipolar Depression, Manic Depression

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Uridine
Placebo
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Bipolar Disorder focused on measuring Adolescent, Bipolar Disorder, Bipolar Depression, Manic Depression, Neuroimaging, Magnetic Resonance Spectroscopy, Uridine, Pyrimidines

Eligibility Criteria

13 Years - 21 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

No Intervention

Arm Label

Uridine

Placebo

Healthy Comparison

Arm Description

Subjects randomized to this study arm will receive uridine 500 mg twice daily by mouth for 6 weeks.

Subjects randomized to this arm of the study will receive placebo 500 mg twice daily by mouth for 6 weeks.

Subjects are not randomized, and do not receive any treatment intervention.

Outcomes

Primary Outcome Measures

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).
Magnetic Resonance Spectroscopy is a safe, non-invasive method for measuring brain chemicals thought to be involved in mood disorders, such as GLX (glutamate + glutamine). Previous research indicates that adolescents with bipolar depression have elevated Glx concentrations, compared with controls. The measurement of Glx with 1H-MRS has the potential to identify translational biomarkers of juvenile BD pathophysiology and treatment response.
Change in Children's Depression Rating Scale-Revised (CDRS-R) Score.
The CDRS-R is a brief rating scale based on a semi-structured interview with the participant (and/or their parent or guardian). The scale can be administered and scored in under 30 minutes. The CDRS-R gives you a single summary score -- with an interpretation of, and clinical recommendations for, six different score ranges. Total possible scores range from 17 to 113, with higher scores indicating more depressive symptoms reported by the participant (and/or their parent or guardian).

Secondary Outcome Measures

Columbia-Suicide Severity Rating Scale (C-SSRS)
The Columbia-Suicide Severity Rating Scale (C-SSRS) is used to measure suicidal thoughts and behaviors in Investigational New Drug (IND) studies. The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).

Full Information

First Posted
March 1, 2013
Last Updated
March 7, 2018
Sponsor
University of Utah
Collaborators
The Depressive and Bipolar Disorder Alternative Treatment Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01805440
Brief Title
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

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah
Collaborators
The Depressive and Bipolar Disorder Alternative Treatment Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder, Bipolar Depression, Manic Depression
Keywords
Adolescent, Bipolar Disorder, Bipolar Depression, Manic Depression, Neuroimaging, Magnetic Resonance Spectroscopy, Uridine, Pyrimidines

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Uridine
Arm Type
Active Comparator
Arm Description
Subjects randomized to this study arm will receive uridine 500 mg twice daily by mouth for 6 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to this arm of the study will receive placebo 500 mg twice daily by mouth for 6 weeks.
Arm Title
Healthy Comparison
Arm Type
No Intervention
Arm Description
Subjects are not randomized, and do not receive any treatment intervention.
Intervention Type
Drug
Intervention Name(s)
Uridine
Intervention Description
Uridine is the active treatment in this clinical trial.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Pill Placebo
Intervention Description
Pill placebo is the inactive treatment comparator in this clinical trial.
Primary Outcome Measure Information:
Title
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).
Description
Magnetic Resonance Spectroscopy is a safe, non-invasive method for measuring brain chemicals thought to be involved in mood disorders, such as GLX (glutamate + glutamine). Previous research indicates that adolescents with bipolar depression have elevated Glx concentrations, compared with controls. The measurement of Glx with 1H-MRS has the potential to identify translational biomarkers of juvenile BD pathophysiology and treatment response.
Time Frame
Baseline and 6 weeks
Title
Change in Children's Depression Rating Scale-Revised (CDRS-R) Score.
Description
The CDRS-R is a brief rating scale based on a semi-structured interview with the participant (and/or their parent or guardian). The scale can be administered and scored in under 30 minutes. The CDRS-R gives you a single summary score -- with an interpretation of, and clinical recommendations for, six different score ranges. Total possible scores range from 17 to 113, with higher scores indicating more depressive symptoms reported by the participant (and/or their parent or guardian).
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
The Columbia-Suicide Severity Rating Scale (C-SSRS) is used to measure suicidal thoughts and behaviors in Investigational New Drug (IND) studies. The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Kondo, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Informed Consent to publicly share individual participant data, e.g. MRI and MRS brain scans, was not obtained.
Citations:
PubMed Identifier
21486171
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.
Results Reference
background
Links:
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080753/
Description
Free downloadable full-text article

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Uridine Adolescent Bipolar Depression Randomized Controlled Trial

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