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
|Condition or disease||Intervention/treatment||Phase|
|Bipolar Disorder||Drug: JNJ-18038683||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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)|
|Study Start Date :||September 2015|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||October 2019|
Subjects will be randomized to receive JNJ-18038683 or placebo after the completion of the baseline assessments. Subjects randomized to JNJ-18038683 will receive 10 mg for one week, then titrate to 20 mg for the duration of the trial, with the provision for a single, downward dose adjustment for intolerance, based upon investigator judgment.
JNJ-18038683 10-20 mg/day for 8 weeks
Placebo Comparator: Placebo
Placebo treatment for 8 weeks.
JNJ-18038683 10-20 mg/day for 8 weeks
- 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
- Montgomery-Asberg Depression Rating Scale [ Time Frame: 8 weeks ]Secondary outcome measures will include cognition composite score, the MADRS total score (for those with a MADRS score between 8 and 20 at the time of enrollment)
- Functional ability and clinical global severity scores as additional endpoints [ Time Frame: 8 weeks ]We will assess JNJ-18038683 effects on functional ability and clinical global severity scores as additional endpoints, as measured by the SLOF and CGI-BP
- Drug tolerability [ Time Frame: 8 weeks ]we will analyze the effect on drug tolerability as determined by the following: body weight (LBS), body mass index (BMI), waist circumference(INCHES), and movement rating scale (AIMS)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02466685
|Contact: Mostafa Hassan, BAemail@example.com|
|Contact: Ahmad Elzokaky, BAfirstname.lastname@example.org|
|United States, Illinois|
|Northwestern University Psychiatric Clinical Research Program||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Cale Wardell 312-503-9076 email@example.com|
|Principal Investigator:||Herbert Y Meltzer, MD||Northwestern University|