Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients
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ClinicalTrials.gov Identifier: NCT02466685 |
Recruitment Status :
Recruiting
First Posted : June 9, 2015
Last Update Posted : July 19, 2019
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Tracking Information | |||||||||
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First Submitted Date ICMJE | June 4, 2015 | ||||||||
First Posted Date ICMJE | June 9, 2015 | ||||||||
Last Update Posted Date | July 19, 2019 | ||||||||
Study Start Date ICMJE | September 2015 | ||||||||
Estimated Primary Completion Date | July 2019 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Comprehensive cognition battery [ Time Frame: 8 weeks ] measuring executive functioning, speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
Montgomery-Asberg Depression Rating Scale [ Time Frame: 8 weeks ] | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients | ||||||||
Official Title ICMJE | Testing the Ability of JNJ-18038683, a Selective Serotonin (5-HT)7 Antagonist, to Improve Cognition and Reduce Residual Depressive Symptoms in Stable Bipolar Patients (18038683BCD2001) | ||||||||
Brief Summary | The goals of this study are to evaluate the efficacy of JNJ-18038683 in an 8 week trial to ameliorate the cognitive deficit and reduce residual depressive symptoms in 60 stable bipolar outpatients receiving treatment for depression. JNJ-18038683 will be studied and compared with placebo as adjunctive treatment to standard pharmacologic treatment for bipolar disorder. | ||||||||
Detailed Description | Most, but not all, patients with bipolar disorder (BPD) have clinically significant cognitive impairment. Impairment is present in both the manic and depressed phases of BPD, as well as in euthymic periods. The percentage of BPD patients with cognitive impairment (CIBD) varies among studies, with 40-60% representing the best estimate. The weight of the evidence supports no overall difference in the type and severity of cognitive impairment in any phase of BPD, i.e. it is a stable trait feature of BPD, albeit variable from one patient to another. The most commonly affected cognitive domains are speed of processing, declarative memory, attention and working memory. Although CIBD is milder in severity than the cognitive impairment associated with schizophrenia (CIAS), on average, as in schizophrenia, CIBD has a major impact on function and quality of life in most patients, particularly because the greater preservation of function of BPD enables them to engage in activities which are more dependent on intact cognitive function. Thus, it is highly likely that improvement in CIBD will have valuable clinical benefit, especially with regard to quality of life measures. It is reasonable to predict that treatments effective to improve CIBD could also be beneficial for CIAS. Efficacy for cognitive impairment is likely to be greater in BPD than schizophrenia, because the baseline severity is milder in the former. Despite this strong rationale for targeting CIBD, there has been minimal focus on clinical trials to improve CIBD, perhaps because so many resources have been devoted to the effort to treat CIAS, but lack of appreciation of the severity of CIBD and its importance as a determinant of functional outcome in BPD may be the most important factors. In a recent study of CIBD, using the MATRICS Consensus Cognitive Battery (MCCB), impairment was found in both treatment resistant BP I and II depressed inpatients within all MCCB domains. The greatest impairment was evident in speed of processing, declarative memory and attention. The impairment was numerically greater in BP I than BP II patients but the difference was not significant. Compared to normal controls, the deficits, in BP 1 patients, in speed of processing was 1.2SD, in attention, 1.0 SD, and in verbal learning, 1.8 SD. The least affected domain was visual learning, with a mean deficit of 0.8SD compared to normal controls. The mean composite score deficit was 1.25 SD. Medication for BPD, particularly mood stabilizers, may adversely affect some domains of cognition in BPD. However, antidepressant medications have not been found to affect the severity of cognitive impairment in major depression or BPD. Based on the pre-clinical, pro-cognitive effects of 5-HT7 antagonism in our laboratory, along with the reported pre-clinical antidepressant effects of JNJ-18038683, we propose to conduct a randomized, placebo- controlled parallel, design study to assess the effects of JNJ-18038683 on multiple domains of cognition and mood symptoms. Since our preclinical studies show that 5-HT7 receptor blockade is highly effective in improving declarative memory in rodents, the declarative memory measures will be the primary outcome measures. Due to the effect of JNJ-18038683 on depressive symptoms in preclinical paradigms, we will investigate the following in the clinical trial the potential antidepressant effect of JNJ-18038683 on patients with baseline MADRS score between 8 and 20. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Bipolar Disorder | ||||||||
Intervention ICMJE | Drug: JNJ-18038683
JNJ-18038683 10-20 mg/day for 8 weeks
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
60 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | October 2019 | ||||||||
Estimated Primary Completion Date | July 2019 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria
Exclusion Criteria
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 60 Years (Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT02466685 | ||||||||
Other Study ID Numbers ICMJE | 18038683BCD2001 | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product | Not Provided | ||||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||||
Responsible Party | Herbert Meltzer, Northwestern University | ||||||||
Study Sponsor ICMJE | Herbert Meltzer | ||||||||
Collaborators ICMJE | Janssen Research & Development, LLC | ||||||||
Investigators ICMJE |
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PRS Account | Northwestern University | ||||||||
Verification Date | July 2019 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |