Bipolar DisorderPhase 4NCT02456896
Effect of Oxcarbazepine on Serum Brain Derived Neurotrophic Factor (BDNF) in Bipolar Disorder
A Phase 4 study testing Oxcarbazepine in people with Bipolar Disorder, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
Trial summary
The present study has been designed to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Oxcarbazepine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteIndia
- Study dates
- Jun 2015to Dec 2015
- Phase
- Phase 4
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All patients with the diagnosis of bipolar affective disorder (by ICD-10 DCR) current episode mania without psychotic symptoms
- Patients aged 18-45 years, of either sex.
- Patients with baseline score > 20 on the Young Mania Rating Scale (YMRS).
- Patients who had not taken any treatment for at least 4 weeks before inclusion.
Who cannot join
- Patients with bipolar disorder (by ICD-10 DCR) presenting during depressive/euthymic/mixed episode.
- Patients who are already under treatment for the presenting conditions.
- Rapid cycling in the past 12 months.
- Previous history of refractoriness to carbazepine or oxcarbazepine.
- Patients with comorbid substance abuse or history of organicity
- Pregnant and nursing women, patients with history of major medical or neurological illness.
Trial locations and contacts
1 site in 1 country.
India1 site
All India Institute of Medical Sciences (AIIMS)
Bhubaneswar, Odisha, 751019
About this study
The present study has been designed to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect.
Read the detailed description
Bipolar disorder (BD) is a chronic psychiatric illness of partially unknown pathophysiology. BD likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. Abnormalities of neurotrophins (NTs) and other trophic factors orchestrate important alterations which could be implicated in the etiology of BD. As consistently reported in post-mortem studies, these modifications are generally associated with the disruption of distinct subregions and functions of the brain, one of which is the deregulation of neurotrophins.
NTs are capable of signaling neurons, glial cells and other cellular systems to enable survival, differentiation and growth. BDNF is one of the most studied and abundant NTs in the brain, which plays an important role in a variety of neural processes during the development of both animals and humans. Initially, BDNF is important for neurogenesis, neuronal survival, and normal maturation of neural development pathways. In the adult, BDNF is not only important for synaptic plasticity and dendritic growth, but also for long-term memory consolidation. Several studies have proved that BDNF is significantly reduced in manic, hypomanic or depressive stages of BD, whereas euthymic patients exhibit BDNF levels similar to healthy controls.
Rafael T. de Sousa et al have observed a significant increase in serum BDNF levels after 28 days of lithium monotherapy in patients with BD and suggested neuroprotective role of lithium due to its direct regulatory effect on BDNF. Oxcarbazepine is a commonly used mood stabilizer which has demonstrated comparable efficacy to divalproate sodium and better tolerability profile but till date there is no study on its effect on BDNF. The aim of the present study is to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect.
- Conditions
- Bipolar Disorder
- Being tested
- Oxcarbazepine
- Keywords
- Oxcarbazepine, Brain Derived Neurotrophic Factor, Bipolar disorder, Neuroprotection
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxcarbazepineDrug
After baseline assessments, patients in test group will be prescribed Tab. Oxcarbazepine (600mg/daily in two divided dose for 1 week followed by 900mg/daily in two divided dose for next 3 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Healthy control | No intervention | Twenty five (25) age and sex matched healthy individuals will serve as the control group. Control subjects will be evaluated at baseline only. |
| Oxcarbazepine | Experimental | Twenty five (25) patients of bipolar mania will be prescribed oxcarbazepine for 4 weeks. Receives: Drug: Oxcarbazepine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum Brain Derived Neurotrophic Factor (BDNF)
Serum BDNF was estimated by ELISA using human BDNF ELISA kit from Boster Biological Technology Co. Ltd., Pleasanton, CA.
Measured: Baseline and 4 weeks
Secondary outcomes (1)
Correlation Between Young Mania Rating Scale (YMRS) and Serum Brain Derived Neurotrophic Factor (BDNF)
The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania.
Spearman's rank correlation coefficient (Spearman's ρ) was calculated for measuring correlation between YMRS score and serum BDNF.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study startJun 2015
- 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 (9)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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences, Bhubaneswar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar
- Investigators
- DEBASISH HOTA, MD, DM, Study director, AIIMS, Bhubaneswar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456896
- Sponsor's protocol ID
- T/IM-NF/Pharm/14/19
- Status last verified
- Apr 2019
- First submitted
- 27 May 2015
- Last updated
- 7 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Frey BN, Andreazza AC, Houenou J, Jamain S, Goldstein BI, Frye MA, Leboyer M, Berk M, Malhi GS, Lopez-Jaramillo C, Taylor VH, Dodd S, Frangou S, Hall GB, Fernandes BS, Kauer-Sant'Anna M, Yatham LN, Kapczinski F, Young LT. Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust N Z J Psychiatry. 2013 Apr;47(4):321-32. doi: 10.1177/0004867413478217. Epub 2013 Feb 14.
PubMed 23411094Mufson EJ, Kroin JS, Sendera TJ, Sobreviela T. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol. 1999 Feb;57(4):451-84. doi: 10.1016/s0301-0082(98)00059-8.
PubMed 10080385Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736. doi: 10.1146/annurev.neuro.24.1.677.
PubMed 11520916Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381-91. doi: 10.1016/s0959-4388(00)00092-1.
PubMed 10851172Post RM. Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications. J Psychiatr Res. 2007 Dec;41(12):979-90. doi: 10.1016/j.jpsychires.2006.09.009. Epub 2007 Jan 18.
PubMed 17239400Cunha AB, Frey BN, Andreazza AC, Goi JD, Rosa AR, Goncalves CA, Santin A, Kapczinski F. Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett. 2006 May 8;398(3):215-9. doi: 10.1016/j.neulet.2005.12.085. Epub 2006 Feb 9.
PubMed 16480819Fernandes BS, Gama CS, Cereser KM, Yatham LN, Fries GR, Colpo G, de Lucena D, Kunz M, Gomes FA, Kapczinski F. Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J Psychiatr Res. 2011 Aug;45(8):995-1004. doi: 10.1016/j.jpsychires.2011.03.002. Epub 2011 May 6.
PubMed 21550050de Sousa RT, van de Bilt MT, Diniz BS, Ladeira RB, Portela LV, Souza DO, Forlenza OV, Gattaz WF, Machado-Vieira R. Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: a preliminary 4-week study. Neurosci Lett. 2011 Apr 20;494(1):54-6. doi: 10.1016/j.neulet.2011.02.054. Epub 2011 Mar 6.
PubMed 21362460Kakkar AK, Rehan HS, Unni KE, Gupta NK, Chopra D, Kataria D. Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study. Eur Psychiatry. 2009 Apr;24(3):178-82. doi: 10.1016/j.eurpsy.2008.12.014. Epub 2009 Mar 25.
PubMed 19324530
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oxcarbazepine on Serum Brain Derived Neurotrophic Factor (BDNF) in Bipolar Disorder
- ClinicalTrials.gov ID
- NCT02456896
- Acronym / sponsor ID
- T/IM-NF/Pharm/14/19
- Conditions
- Bipolar Disorder
- Keywords
- Oxcarbazepine, Brain Derived Neurotrophic Factor, Bipolar disorder, Neuroprotection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- All India Institute of Medical Sciences, BhubaneswarUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 29 May 2015 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study has been designed to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect.
Detailed description
Bipolar disorder (BD) is a chronic psychiatric illness of partially unknown pathophysiology. BD likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. Abnormalities of neurotrophins (NTs) and other trophic factors orchestrate important alterations which could be implicated in the etiology of BD. As consistently reported in post-mortem studies, these modifications are generally associated with the disruption of distinct subregions and functions of the brain, one of which is the deregulation of neurotrophins.
NTs are capable of signaling neurons, glial cells and other cellular systems to enable survival, differentiation and growth. BDNF is one of the most studied and abundant NTs in the brain, which plays an important role in a variety of neural processes during the development of both animals and humans. Initially, BDNF is important for neurogenesis, neuronal survival, and normal maturation of neural development pathways. In the adult, BDNF is not only important for synaptic plasticity and dendritic growth, but also for long-term memory consolidation. Several studies have proved that BDNF is significantly reduced in manic, hypomanic or depressive stages of BD, whereas euthymic patients exhibit BDNF levels similar to healthy controls.
Rafael T. de Sousa et al have observed a significant increase in serum BDNF levels after 28 days of lithium monotherapy in patients with BD and suggested neuroprotective role of lithium due to its direct regulatory effect on BDNF. Oxcarbazepine is a commonly used mood stabilizer which has demonstrated comparable efficacy to divalproate sodium and better tolerability profile but till date there is no study on its effect on BDNF. The aim of the present study is to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy control | No intervention | –Twenty five (25) age and sex matched healthy individuals will serve as the control group. Control subjects will be evaluated at baseline only. |
| Oxcarbazepine | Experimental | Drug: OxcarbazepineTwenty five (25) patients of bipolar mania will be prescribed oxcarbazepine for 4 weeks. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- All patients with the diagnosis of bipolar affective disorder (by ICD-10 DCR) current episode mania without psychotic symptoms
- Patients aged 18-45 years, of either sex.
- Patients with baseline score > 20 on the Young Mania Rating Scale (YMRS).
- Patients who had not taken any treatment for at least 4 weeks before inclusion.
Key exclusion criteria (6 listed)
- Patients with bipolar disorder (by ICD-10 DCR) presenting during depressive/euthymic/mixed episode.
- Patients who are already under treatment for the presenting conditions.
- Rapid cycling in the past 12 months.
- Previous history of refractoriness to carbazepine or oxcarbazepine.
- Patients with comorbid substance abuse or history of organicity
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 |
|---|---|---|
| OxcarbazepineAfter baseline assessments, patients in test group will be prescribed Tab. Oxcarbazepine (600mg/daily in two divided dose for 1 week followed by 900mg/daily in two divided dose for next 3 weeks). | Drug | Oxcarbazepine |
Primary outcome
Change in Serum Brain Derived Neurotrophic Factor (BDNF)
Time frame: Baseline and 4 weeks
Serum BDNF was estimated by ELISA using human BDNF ELISA kit from Boster Biological Technology Co. Ltd., Pleasanton, CA.
1 secondary outcome
Correlation Between Young Mania Rating Scale (YMRS) and Serum Brain Derived Neurotrophic Factor (BDNF)
Time frame: At baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23411094Frey BN, Andreazza AC, Houenou J, Jamain S, Goldstein BI, Frye MA, Leboyer M, Berk M, Malhi GS, Lopez-Jaramillo C, Taylor VH, Dodd S, Frangou S, Hall GB, Fernandes BS, Kauer-Sant'Anna M, Yatham LN, Kapczinski F, Young LT. Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust N Z J Psychiatry. 2013 Apr;47(4):321-32. doi: 10.1177/0004867413478217. Epub 2013 Feb 14.
- Background: PubMed 10080385Mufson EJ, Kroin JS, Sendera TJ, Sobreviela T. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol. 1999 Feb;57(4):451-84. doi: 10.1016/s0301-0082(98)00059-8.
- Background: PubMed 11520916Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736. doi: 10.1146/annurev.neuro.24.1.677.
- Background: PubMed 10851172Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381-91. doi: 10.1016/s0959-4388(00)00092-1.
- Background: PubMed 17239400Post RM. Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications. J Psychiatr Res. 2007 Dec;41(12):979-90. doi: 10.1016/j.jpsychires.2006.09.009. Epub 2007 Jan 18.
- Background: PubMed 16480819Cunha AB, Frey BN, Andreazza AC, Goi JD, Rosa AR, Goncalves CA, Santin A, Kapczinski F. Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett. 2006 May 8;398(3):215-9. doi: 10.1016/j.neulet.2005.12.085. Epub 2006 Feb 9.
- Background: PubMed 21550050Fernandes BS, Gama CS, Cereser KM, Yatham LN, Fries GR, Colpo G, de Lucena D, Kunz M, Gomes FA, Kapczinski F. Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J Psychiatr Res. 2011 Aug;45(8):995-1004. doi: 10.1016/j.jpsychires.2011.03.002. Epub 2011 May 6.
- Background: PubMed 21362460de Sousa RT, van de Bilt MT, Diniz BS, Ladeira RB, Portela LV, Souza DO, Forlenza OV, Gattaz WF, Machado-Vieira R. Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: a preliminary 4-week study. Neurosci Lett. 2011 Apr 20;494(1):54-6. doi: 10.1016/j.neulet.2011.02.054. Epub 2011 Mar 6.
- Background: PubMed 19324530Kakkar AK, Rehan HS, Unni KE, Gupta NK, Chopra D, Kataria D. Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study. Eur Psychiatry. 2009 Apr;24(3):178-82. doi: 10.1016/j.eurpsy.2008.12.014. Epub 2009 Mar 25.
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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.
DEBASISH HOTA, MD, DM study director
AIIMS, Bhubaneswar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oxcarbazepine in people with Bipolar Disorder, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
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 4 inclusion and 6 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 7 May 2019. 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 India. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 16 Apr 2019). 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 Serum Brain Derived Neurotrophic Factor (BDNF) (time frame: Baseline and 4 weeks). 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 NCT02456896, which also lists 9 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 7 May 2019.