Bipolar DisorderNCT01805440
Uridine Adolescent Bipolar Depression Randomized Controlled Trial
A study testing Uridine in people with Bipolar Disorder and Bipolar Depression, run by University of Utah at 1 site in United States.
Trial 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"). Read more about this study
- Who is it for?
- Ages 13 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder, Bipolar Depression, Manic Depression
- What is being tested?
- Uridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Dec 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Placebo-Controlled Study of Uridine for Adolescent Bipolar Depression: a Magnetic Resonance Spectroscopy Study
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.
Read the 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.
- Conditions
- Bipolar Disorder, Bipolar Depression, Manic Depression
- Being tested
- Uridine, Placebo
- Keywords
- Adolescent, Bipolar Disorder, Bipolar Depression, Manic Depression, Neuroimaging, Magnetic Resonance Spectroscopy, Uridine, Pyrimidines
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UridineDrug
Uridine is the active treatment in this clinical trial.
PlaceboDrug
Also called Pill Placebo
Pill placebo is the inactive treatment comparator in this clinical trial.
| Study group | Role | What they receive |
|---|---|---|
| Uridine | Active comparator | Subjects randomized to this study arm will receive uridine 500 mg twice daily by mouth for 6 weeks. Receives: Drug: Uridine |
| Placebo | Placebo comparator | Subjects randomized to this arm of the study will receive placebo 500 mg twice daily by mouth for 6 weeks. Receives: Drug: Placebo |
| Healthy Comparison | No intervention | Subjects are not randomized, and do not receive any treatment intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 weeks
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).
Measured: 6 weeks
Secondary outcomes (1)
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).
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2013 (estimated)
- Study startAug 2013
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- The Depressive and Bipolar Disorder Alternative Treatment Foundation
- Responsible party
- Principal investigator, Douglas Kondo, MD, University of Utah
- Investigators
- Douglas Kondo, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01805440
- Sponsor's protocol ID
- University of Utah
- Status last verified
- Mar 2018
- First submitted
- 1 Mar 2013
- Last updated
- 12 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Informed Consent to publicly share individual participant data, e.g. MRI and MRS brain scans, was not obtained.
Publications
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.
PubMed 21486171
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-Controlled Study of Uridine for Adolescent Bipolar Depression: a Magnetic Resonance Spectroscopy Study
- ClinicalTrials.gov ID
- NCT01805440
- Acronym / sponsor ID
- University of Utah
- Conditions
- Bipolar Disorder, Bipolar Depression, Manic Depression
- Keywords
- Adolescent, Bipolar Disorder, Bipolar Depression, Manic Depression, Neuroimaging, Magnetic Resonance Spectroscopy, Uridine, Pyrimidines
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- The Depressive and Bipolar Disorder Alternative Treatment Foundation
- Study start
- Aug 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 6 Mar 2013 (estimated)
- Results
- Posted 12 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Uridine | Active comparator | Drug: UridineSubjects randomized to this study arm will receive uridine 500 mg twice daily by mouth for 6 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to this arm of the study will receive placebo 500 mg twice daily by mouth for 6 weeks. |
| Healthy Comparison | No intervention | –Subjects are not randomized, and do not receive any treatment intervention. |
Who may qualify
- Ages
- 13 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UridineUridine is the active treatment in this clinical trial. | Drug | Uridine |
| PlaceboAlso: Pill PlaceboPill placebo is the inactive treatment comparator in this clinical trial. | Drug | Placebo |
Primary outcome
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).
Time frame: Baseline and 6 weeks
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.
Time frame: 6 weeks
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).
1 secondary outcome
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21486171Kondo 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.
- Free downloadable full-text articleLink provided by the sponsor.
- Individual participant dataSharing planned: No. Informed Consent to publicly share individual participant data, e.g. MRI and MRS brain scans, was not obtained.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas Kondo, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Uridine in people with Bipolar Disorder and Bipolar Depression, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). (time frame: Baseline and 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01805440, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2018.