Bipolar DisorderPhase 2NCT00854737
Cytidine and Omega-3 Fatty Acids in Bipolar Disorder
A Phase 2 study testing cytidine and omega-3 fatty acids in people with Bipolar Disorder, run by Mclean Hospital at 2 sites in United States.
Trial summary
The goal of the proposed clinical trial is to assess the effect of oral cytidine and omega-3 fatty acids (O3FA) on bipolar disorder symptoms. This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- cytidine and omega-3 fatty acids
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2004to Jul 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- bipolar disorder
- mood episode within past year
- stable medication regimen
Who cannot join
- primary psychiatric disorder other than bipolar disorder
- significant suicide or homicide risk
- unstable medical conditions
- current or planned pregnancy
- lactose intolerance
- medications affecting lipid absorption or metabolism
- clozapine treatment
Trial locations and contacts
2 sites in 1 country.
United States2 sites
McLean Hospital
Belmont, Massachusetts, 02478
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753
About this study
Official title: A Combination of Cytidine and Omega-3 Fatty Acids in Bipolar Disorder: Are There Additive or Synergistic Mood Stabilizing Effects?
The goal of the proposed clinical trial is to assess the effect of oral cytidine and omega-3 fatty acids (O3FA) on bipolar disorder symptoms. This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill subjects with bipolar disorder. During the 16 week period of the study, subjects are assigned to one of three groups: 1) omega-3 fatty acids + cytidine supplementation, 2) omega-3 fatty acids supplementation alone, and 3) placebo supplementation.
Read the detailed description
Previous studies examining the effect of omega-3 fatty acids on bipolar depression have had mixed results. Some studies have found that omega-3 fatty acids have a positive effect on bipolar depression symptoms, while other studies have found no difference between placebo and omega-3 fatty acid treatment.
The variable effects noted with omega-3 fatty acids may be due in part to a real effect with limited potency. Larger effects might be achieved by combining agents with synergistic effects.
Cytidine is necessary to form key intermediates in the biosynthesis of the phospholipids phosphatidylcholine and phosphatidylethanolamine, which are major components of eukaryotic cell membranes. Recent human studies by our group have shown that CDP-choline (a compound composed of cytidine and choline) can modify brain phospholipid synthesis in healthy adults and may have antidepressant effects (Babb et al., 1996; Babb et al., 2002; Carlezon et al., 2002; Renshaw et al., 1999). The combination of omega-fatty acids and the related pyrimidine, uridine, was associated with enhanced antidepressant-like activity in rats (Carlezon et al., 2005). Thus, the combination of omega-3 fatty acid and cytidine, which is interconverted with uridine in the body, may provide a safe and powerful way to treat bipolar disorder, especially bipolar depression.
This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill subjects with bipolar disorder. During the 16 week period of the study, subjects are assigned to one of three groups: 1) omega-3 fatty acids + cytidine supplementation, 2) omega-3 fatty acids supplementation alone, and 3) placebo supplementation.
- Conditions
- Bipolar Disorder
- Being tested
- cytidine, omega-3 fatty acids, placebo
- Keywords
- bipolar disorder, bipolar depression, bipolar mania, manic depression, depression, mania, hypomania
- Medical subject headings
- Bipolar Disorder, Depression, Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytidineDietary supplement
cytidine (2g po daily for 4 months)
omega-3 fatty acidsDietary supplement
omega-3 fatty acids (4g po daily for 4 months)
placeboDrug
Also called arm 2 and 3
sugar pill
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Omega-3 fatty acid and cytidine supplementation Receives: Dietary Supplement: cytidine; Dietary Supplement: omega-3 fatty acids |
| 2 | Active comparator | omega-3 fatty acid supplementation Receives: Dietary Supplement: omega-3 fatty acids |
| placebo | Placebo comparator | placeno or sugar pill Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mood Rating Scale Scores
Measured: weekly-biweekly
Secondary outcomes (2)
Study Retention Time
Measured: 4 months
functional recovery
Measured: weekly-biweekly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2009 (estimated)
- Study startJul 2004
- Primary completionAug 2007
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Principal investigator, Beth L. Murphy MD, PhD, Mclean Hospital
- Investigators
- Beth L Murphy, MD, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00854737
- Sponsor's protocol ID
- 2009-P-000149
- Status last verified
- Apr 2012
- First submitted
- 27 Feb 2009
- Last updated
- 20 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Babb SM, Appelmans KE, Renshaw PF, Wurtman RJ, Cohen BM. Differential effect of CDP-choline on brain cytosolic choline levels in younger and older subjects as measured by proton magnetic resonance spectroscopy. Psychopharmacology (Berl). 1996 Sep;127(2):88-94. doi: 10.1007/BF02805979.
PubMed 8888372Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002 May;161(3):248-54. doi: 10.1007/s00213-002-1045-y. Epub 2002 Mar 22.
PubMed 12021827Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50. doi: 10.1016/j.biopsych.2004.11.038.
PubMed 15705349Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999 May;56(5):407-12. doi: 10.1001/archpsyc.56.5.407.
PubMed 10232294Carlezon WA, Pliakas AM, Parow AM, Detke MJ, Cohen BM, Renshaw PF. Antidepressant-like effects of cytidine in the forced swim test in rats. Biol Psychiatry. 2002 Jun 1;51(11):882-9. doi: 10.1016/s0006-3223(01)01344-0.
PubMed 12022961Murphy BL, Stoll AL, Harris PQ, Ravichandran C, Babb SM, Carlezon WA Jr, Cohen BM. Omega-3 fatty acid treatment, with or without cytidine, fails to show therapeutic properties in bipolar disorder: a double-blind, randomized add-on clinical trial. J Clin Psychopharmacol. 2012 Oct;32(5):699-703. doi: 10.1097/JCP.0b013e318266854c.
PubMed 22926607
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combination of Cytidine and Omega-3 Fatty Acids in Bipolar Disorder: Are There Additive or Synergistic Mood Stabilizing Effects?
- ClinicalTrials.gov ID
- NCT00854737
- Acronym / sponsor ID
- 2009-P-000149
- Conditions
- Bipolar Disorder
- Keywords
- bipolar disorder, bipolar depression, bipolar mania, manic depression, depression, mania, hypomania
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- Jul 2004
- Primary completion
- Aug 2007 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 3 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the proposed clinical trial is to assess the effect of oral cytidine and omega-3 fatty acids (O3FA) on bipolar disorder symptoms. This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill subjects with bipolar disorder. During the 16 week period of the study, subjects are assigned to one of three groups: 1) omega-3 fatty acids + cytidine supplementation, 2) omega-3 fatty acids supplementation alone, and 3) placebo supplementation.
Detailed description
Previous studies examining the effect of omega-3 fatty acids on bipolar depression have had mixed results. Some studies have found that omega-3 fatty acids have a positive effect on bipolar depression symptoms, while other studies have found no difference between placebo and omega-3 fatty acid treatment.
The variable effects noted with omega-3 fatty acids may be due in part to a real effect with limited potency. Larger effects might be achieved by combining agents with synergistic effects.
Cytidine is necessary to form key intermediates in the biosynthesis of the phospholipids phosphatidylcholine and phosphatidylethanolamine, which are major components of eukaryotic cell membranes. Recent human studies by our group have shown that CDP-choline (a compound composed of cytidine and choline) can modify brain phospholipid synthesis in healthy adults and may have antidepressant effects (Babb et al., 1996; Babb et al., 2002; Carlezon et al., 2002; Renshaw et al., 1999). The combination of omega-fatty acids and the related pyrimidine, uridine, was associated with enhanced antidepressant-like activity in rats (Carlezon et al., 2005). Thus, the combination of omega-3 fatty acid and cytidine, which is interconverted with uridine in the body, may provide a safe and powerful way to treat bipolar disorder, especially bipolar depression.
This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill subjects with bipolar disorder. During the 16 week period of the study, subjects are assigned to one of three groups: 1) omega-3 fatty acids + cytidine supplementation, 2) omega-3 fatty acids supplementation alone, and 3) placebo supplementation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Dietary Supplement: cytidine, Dietary Supplement: omega-3 fatty acidsOmega-3 fatty acid and cytidine supplementation |
| 2 | Active comparator | Dietary Supplement: omega-3 fatty acidsomega-3 fatty acid supplementation |
| placebo | Placebo comparator | Drug: placeboplaceno or sugar pill |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- bipolar disorder
- mood episode within past year
- stable medication regimen
Key exclusion criteria (7 listed)
- primary psychiatric disorder other than bipolar disorder
- significant suicide or homicide risk
- unstable medical conditions
- current or planned pregnancy
- lactose intolerance
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 |
|---|---|---|
| cytidinecytidine (2g po daily for 4 months) | Dietary supplement | 1 |
| omega-3 fatty acidsomega-3 fatty acids (4g po daily for 4 months) | Dietary supplement | 1, 2 |
| placeboAlso: arm 2 and 3sugar pill | Drug | placebo |
Primary outcome
Mood Rating Scale Scores
Time frame: weekly-biweekly
2 secondary outcomes
Study Retention Time
Time frame: 4 months
functional recovery
Time frame: weekly-biweekly
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2012.
- Background: PubMed 8888372Babb SM, Appelmans KE, Renshaw PF, Wurtman RJ, Cohen BM. Differential effect of CDP-choline on brain cytosolic choline levels in younger and older subjects as measured by proton magnetic resonance spectroscopy. Psychopharmacology (Berl). 1996 Sep;127(2):88-94. doi: 10.1007/BF02805979.
- Background: PubMed 12021827Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002 May;161(3):248-54. doi: 10.1007/s00213-002-1045-y. Epub 2002 Mar 22.
- Background: PubMed 15705349Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50. doi: 10.1016/j.biopsych.2004.11.038.
- Background: PubMed 10232294Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999 May;56(5):407-12. doi: 10.1001/archpsyc.56.5.407.
- Background: PubMed 12022961Carlezon WA, Pliakas AM, Parow AM, Detke MJ, Cohen BM, Renshaw PF. Antidepressant-like effects of cytidine in the forced swim test in rats. Biol Psychiatry. 2002 Jun 1;51(11):882-9. doi: 10.1016/s0006-3223(01)01344-0.
- Derived from this study: PubMed 22926607Murphy BL, Stoll AL, Harris PQ, Ravichandran C, Babb SM, Carlezon WA Jr, Cohen BM. Omega-3 fatty acid treatment, with or without cytidine, fails to show therapeutic properties in bipolar disorder: a double-blind, randomized add-on clinical trial. J Clin Psychopharmacol. 2012 Oct;32(5):699-703. doi: 10.1097/JCP.0b013e318266854c.
- hospital website with links to research group and studiesLink 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.
Beth L Murphy, MD, PhD principal investigator
Mclean Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cytidine and omega-3 fatty acids in people with Bipolar Disorder, run by Mclean Hospital at 2 sites 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 3 inclusion and 7 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 20 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Mood Rating Scale Scores (time frame: weekly-biweekly). 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 NCT00854737, which also lists 6 linked publications.
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 20 Apr 2012.