Bipolar DisorderPhase 2NCT00841269
Oral Uridine for Treatment of Bipolar Depression in Adolescents
A Phase 2 study testing Uridine in people with Bipolar Disorder, run by University of Utah at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Uridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Jun 2013
- Phase
- Phase 2
- 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 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Participants must meet DSM-IV-TR (American Psychiatric Association, 2000) criteria for Bipolar Disorder Type I, Type II, or Not Otherwise Specified (NOS) with current mood state depressed for > 2 weeks
- Participants must be between the age of 13 and 18 years
- Participants who enter the study on psychotropic medications must be on a regimen that has been stable for > 2 weeks at the time of study entry
- Participants must be able to give informed consent or assent, and parent(s)/guardian(s) must be able to give informed permission for study participation
- Participants must be between the ages of 13 and 18 years
- Participants must not meet DSM-IV-TR diagnostic criteria for a mental disorder or substance abuse
- Participants must be able to give informed consent or assent and parents/guardians must be able to give informed permission for participation
Who cannot join
- Adolescents with an unstable co-morbid medical, neurological, or psychiatric disorder
- Pregnant females, nursing mothers, or females of childbearing potential who are unable or unwilling to practice contraception during the study
- Participants with high risk of suicidal behaviors, homicidal behaviors, or self-harm
- Participants who in the opinion of the investigator are unlikely to be able to comply with the study protocol
- Participants who meet DSM-IV-TR criteria for current substance abuse or substance dependence, with the exception of nicotine abuse or dependence
- Participants for whom the MRI/MRS scans are contraindicated, such as children with ferromagnetic implants or claustrophobia
Show all 15Show fewer
- Participants whose mood state is manic
- Documented or suspected history of mental retardation (IQ<70)
- Positive urine drug screen for cocaine or amphetamines
- Known hypersensitivity to uridine
- Selection of Healthy Volunteers:
- Clinically significant medical, neurological, psychiatric or substance abuse disorder
- Pregnant subjects, due to the unknown effects of MRI/MRS scans on a fetus. In addition, women of childbearing potential who are unable or unwilling to practice contraception during the study will be excluded. Female participants who are of child-bearing potential must have a negative urine pregnancy test before each MRI/MRS scan.
- Participants with a contraindication to MRI/MRS scanning, such as a metallic implant
- Patients unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Utah School of Medicine
Salt Lake City, Utah, 84108
About this study
Official title: Oral Administration of Uridine for Treatment of Bipolar Depression in Adolescents: A Magnetic Resonance Spectroscopy Study
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.
Read the 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.
- Conditions
- Bipolar Disorder
- Being tested
- Uridine
- Keywords
- Bipolar Manic Depression
- 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 500 mg by mouth twice per day for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Uridine | Experimental | Uridine 500 mg by mouth twice daily for 6 weeks Receives: Drug: Uridine |
| Healthy Comparison | No intervention | Healthy comparison participants were seen for baseline and week 6 MRI scans. No treatment was administered to participants enrolled as healthy comparisons. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Scores in Children's Depression Rating Scale (CDRS-R), Assessed Before and After 6 Week Uridine Treatment
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.
Measured: 6 weeks
The Primary Neuroimaging Outcome Will be Changes in Beta-NTP to TP (Total Phosphorus) Ratio in the Anterior Cingulate.
Measured: 6 weeks
Secondary outcomes (1)
A Secondary Outcome Measure Includes a Change in Young Mania Rating Scale (YMRS) Score
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.
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 posted11 Feb 2009 (estimated)
- Study startMay 2009
- Primary completionJun 2013
- Study completionJun 2013
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.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Douglas Kondo, MD, University of Utah
- Investigators
- Douglas G Kondo, M.D., Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841269
- Sponsor's protocol ID
- 28455
- Other IDs
- 5R01MH058681-06
- Status last verified
- Feb 2018
- First submitted
- 9 Feb 2009
- Last updated
- 26 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 26 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Administration of Uridine for Treatment of Bipolar Depression in Adolescents: A Magnetic Resonance Spectroscopy Study
- ClinicalTrials.gov ID
- NCT00841269
- Acronym / sponsor ID
- 28455
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Manic Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- May 2009
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Posted 8 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Uridine | Experimental | Drug: UridineUridine 500 mg by mouth twice daily for 6 weeks |
| Healthy Comparison | No intervention | –Healthy comparison participants were seen for baseline and week 6 MRI scans. No treatment was administered to participants enrolled as healthy comparisons. |
Who may qualify
- Ages
- 13 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Participants must meet DSM-IV-TR (American Psychiatric Association, 2000) criteria for Bipolar Disorder Type I, Type II, or Not Otherwise Specified (NOS) with current mood state depressed for > 2 weeks
- Participants must be between the age of 13 and 18 years
- Participants who enter the study on psychotropic medications must be on a regimen that has been stable for > 2 weeks at the time of study entry
- Participants must be able to give informed consent or assent, and parent(s)/guardian(s) must be able to give informed permission for study participation
- Participants must be between the ages of 13 and 18 years
Key exclusion criteria (15 listed)
- Adolescents with an unstable co-morbid medical, neurological, or psychiatric disorder
- Pregnant females, nursing mothers, or females of childbearing potential who are unable or unwilling to practice contraception during the study
- Participants with high risk of suicidal behaviors, homicidal behaviors, or self-harm
- Participants who in the opinion of the investigator are unlikely to be able to comply with the study protocol
- Participants who meet DSM-IV-TR criteria for current substance abuse or substance dependence, with the exception of nicotine abuse or dependence
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 500 mg by mouth twice per day for 6 weeks | Drug | Uridine |
Primary outcome
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
1 secondary outcome
A Secondary Outcome Measure Includes a Change in Young Mania Rating Scale (YMRS) Score
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 26 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: 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.
- UtahBrain.orgLink provided by the sponsor.
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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 G Kondo, M.D. 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 Phase 2 study testing Uridine in people with Bipolar Disorder, 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 15 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 26 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2015). 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?
Mean Scores in Children's Depression Rating Scale (CDRS-R), Assessed Before and After 6 Week Uridine Treatment (time frame: 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 NCT00841269, 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 26 Mar 2018.