Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients

October 30, 2023 updated by: Herbert Meltzer

Testing the Ability of JNJ(Janssen and Janssen)18038683, a Selective Serotonin (5-HT)7 Antagonist, to Improve Cognition and Reduce Residual Depressive Symptoms in Stable Bipolar Patients (18038683BCD2001)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine; Department of Psychiatry and Behavioral Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. All participants must have signed an informed consent document indicating they understand the purpose of the study and the procedures required for the study and are willing to participate by complying with the study procedures and restrictions.
  2. Male or female individuals of any race; between 18 to 60 years of age, inclusive.
  3. Resides in a stable living situation, according to the investigator's judgment.
  4. Diagnosis of bipolar disorder I or II for at least 1 year in duration, as established by the SCID-I, and verified with medical records and/or confirmation of diagnosis by treating clinician. Patients will be in a nonacute phase at the time of initial screening and have been so for at least 1 month.
  5. No more than moderate clinical symptom burden severity, as defined by the following: Montgomery Asberg Depression Rating Scale < 20 Young Mania Rating Scale <12
  6. Individuals medically stable enough to complete an 8 week clinical trial, in the judgment of the investigator
  7. Women of childbearing potential must have a negative pregnancy serum test at screening, negative pregnancy urine test at baseline, and agree to use adequate protection (i.e. double barrier method) for birth control.
  8. Antidepressant (AD) medications are allowed if the subject has been treated with a stable dose for at least 2 months before screening.
  9. Individuals receiving a single mood stabilizer (e.g., lithium. valproate, or lamictal) are allowed if a stable dose has been maintained for at least 2 months prior to screening.

  10. Individuals may be receiving one treatment of each the following groups:

    antidepressants, mood stabilizers, and atypical antipsychotics other than clozapine, but not more than one from each group.

  11. Individuals taking ripseridone, lurasidone, or ziprasidone must be currently taking < doses of 3mg, 40mg, and, 80mg, respectively.
  12. Subjects may be treated with inclusionary antipsychotic drugs as long as they are on a stable dose of injectable medication for 2 months or a sable dose of an oral medication for 1 month. Exclusionary antipsychotic drugs are listed in Appendix 2 in the protocol.
  13. Patients with a history of compliance with a drug treatment regimen for bipolar disorder, as noted in medical/psychiatric history.
  14. CNS stimulants (e.g., Adderall, Ritalin) are permitted if the participant is stable on their dosage of medication for 1 month before screening and cannot change dosage throughout the study.
  15. Able to complete cognition assessments in English
  16. Individuals must demonstrate a substantive cognitive deficit, as measured by the Trails A, Hopkins Verbal Learning Test (HVLT), and the Letter Number Span, administered at the screening visit. Eligible individuals will have an established cognitive deficit as measured by one or more of these tests, scoring below the 75th percentile, using comparative norms according to age, gender, and education.
  17. Able to understand and complete cognition assessments

Exclusion Criteria

  1. Failure to perform screening or baseline examinations
  2. Hospitalization within 8 weeks before screening, or change in mood stabilizing or antidepressant medication or dose within 2 months prior to screening.
  3. Individuals who have participated in another clinical study within the past 2 months.
  4. Individuals with tardive dyskinesia.
  5. Individuals with other DSM-V Axis I or Axis II primary diagnoses.
  6. Diagnosis of alcohol or substance use disorder within the past 3 months.
  7. Subject assessed to be at significant suicide risk based on responses to the Columbia Suicide Severity Rating Scale (C-SSRS).
  8. History of myocardial infarction, unstable angina, uncontrolled hypotension or hypertension within 3 months before screening.
  9. Clinically significant abnormality on screening ECG.
  10. Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 times the upper limit of normal (ULN).
  11. History of stroke, brain tumor, head trauma with loss of consciousness, or other clinically significant neurological condition within 12 months before screening.
  12. Individuals with other uncontrolled medical conditions, in the opinion of the investigator.
  13. Use of drugs known to be metabolized by CYP2D6.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: JNJ-18038683
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.
Drug: JNJ-18038683
JNJ-18038683 10-20 mg/day tablet for 8 weeks
Placebo Comparator: Placebo
Placebo treatment for 8 weeks.
Drug: Placebo
placebo tablet daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The 8-week Evaluation of Verbal Fluency Performance After Randomization
Time Frame: Baseline and week 8

Change in a score of Verbal Fluency from baseline to week 8 A higher amount of change represents a better outcome V.F., as a primary outcome measure, is one of the Cognitive battery tests used to evaluate neurocognitive functions, i.e., speed of processing, attention/vigilance, working memory, verbal learning, and visual learning.

The way to calculate the score: the participant is asked to produce as many words as possible from a category in a given time and each correct word gets 1 score Min raw score:0 Max raw score:60
Baseline and week 8

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale
Time Frame: Baseline to week 8

Secondary outcome measures will include mean changes of the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 8.

The MADRS will be utilized to assess a subject's level of depressive symptoms and must be administered using a structured interview guide.

This scale consists of 10 items, each with seven defined grades of severity (zero to six), and min score of 0, and a max score of 60.

Higher values represent a worse outcome. Notably, mean changes were not statistically significant in both groups.
Baseline to week 8
Clinical Global Impression Severity of the Subject With Bipolar Disorder Scale( CGI-S in BP) Change From Baseline to Week 8
Time Frame: Baseline to 8 weeks

We assessed the clinical global Impression severity (CGI-S) scores change in JNJ-18038683 and the placebo group as an additional endpoint.

The scale rates the subject's Severity of Illness (CGI-BPSeverity: mania, depression, and overall bipolar illness). Using ANCOVA analysis to assess changes from baseline to week 8, based on the least-square means and standard errors was the method.

CGI-S scores range from 0 to 7. Higher scores mean a worse outcome.
Baseline to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Herbert Meltzer

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Janssen Research & Development, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Herbert Y Meltzer, MD, Northwestern University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 9, 2015

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18038683BCD2001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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