Bipolar DisorderPhase 2NCT02466685
Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients
A Phase 2 study testing JNJ-18038683 in people with Bipolar Disorder, run by Herbert Meltzer at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- JNJ-18038683
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Dec 2022
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
- Male or female individuals of any race; between 18 to 60 years of age, inclusive.
- Resides in a stable living situation, according to the investigator's judgment.
- 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.
- No more than moderate clinical symptom burden severity, as defined by the following: Montgomery Asberg Depression Rating Scale < 20 Young Mania Rating Scale <12
- Individuals medically stable enough to complete an 8 week clinical trial, in the judgment of the investigator
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- 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.
- Antidepressant (AD) medications are allowed if the subject has been treated with a stable dose for at least 2 months before screening.
- 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.
- 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.
- Individuals taking ripseridone, lurasidone, or ziprasidone must be currently taking < doses of 3mg, 40mg, and, 80mg, respectively.
- 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.
- Patients with a history of compliance with a drug treatment regimen for bipolar disorder, as noted in medical/psychiatric history.
- 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.
- Able to complete cognition assessments in English
- 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.
- Able to understand and complete cognition assessments
Who cannot join
- Failure to perform screening or baseline examinations
- Hospitalization within 8 weeks before screening, or change in mood stabilizing or antidepressant medication or dose within 2 months prior to screening.
- Individuals who have participated in another clinical study within the past 2 months.
- Individuals with tardive dyskinesia.
- Individuals with other DSM-V Axis I or Axis II primary diagnoses.
- Diagnosis of alcohol or substance use disorder within the past 3 months.
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- Subject assessed to be at significant suicide risk based on responses to the Columbia Suicide Severity Rating Scale (C-SSRS).
- History of myocardial infarction, unstable angina, uncontrolled hypotension or hypertension within 3 months before screening.
- Clinically significant abnormality on screening ECG.
- Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 times the upper limit of normal (ULN).
- History of stroke, brain tumor, head trauma with loss of consciousness, or other clinically significant neurological condition within 12 months before screening.
- Individuals with other uncontrolled medical conditions, in the opinion of the investigator.
- Use of drugs known to be metabolized by CYP2D6.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University Feinberg School of Medicine; Department of Psychiatry and Behavioral Sciences
Chicago, Illinois, 60611
About this study
Official title: 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.
Read the 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.
- Conditions
- Bipolar Disorder
- Being tested
- JNJ-18038683, Placebo
- Keywords
- Bipolar, Depression, Cognition, Cognitive
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-18038683Drug
JNJ-18038683 10-20 mg/day tablet for 8 weeks
PlaceboDrug
placebo tablet daily
| Study group | Role | What they receive |
|---|---|---|
| JNJ-18038683 | Experimental | 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. Receives: Drug: JNJ-18038683 |
| Placebo | Placebo comparator | Placebo treatment for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The 8-week Evaluation of Verbal Fluency Performance After Randomization
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
Measured: Baseline and week 8
Secondary outcomes (2)
Montgomery-Asberg Depression Rating Scale
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.
Measured: 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
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.
Measured: Baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2015 (estimated)
- Study startSep 2015
- Primary completionSep 2021
- Study completionDec 2022
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 (1)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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herbert Meltzer
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor-investigator, Herbert Meltzer, Northwestern University
- Investigators
- Herbert Y Meltzer, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02466685
- Sponsor's protocol ID
- 18038683BCD2001
- Status last verified
- Oct 2023
- First submitted
- 4 Jun 2015
- Last updated
- 14 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Arshadi M, Elmaadawi AZ, Nasr S, Jayathilake K, Rassnick S, Ford L, Drevets WC, Meltzer HY. Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder. J Clin Psychopharmacol. 2024 Sep-Oct 01;44(5):481-491. doi: 10.1097/JCP.0000000000001889.
PubMed 39250138
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02466685
- Acronym / sponsor ID
- 18038683BCD2001
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar, Depression, Cognition, Cognitive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Herbert MeltzerUniversity, hospital or other
- Collaborators
- Janssen Research & Development, LLC
- Study start
- Sep 2015
- Primary completion
- Sep 2021 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 9 Jun 2015 (estimated)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| JNJ-18038683 | Experimental | Drug: JNJ-18038683Subjects 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo treatment for 8 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- 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.
- Male or female individuals of any race; between 18 to 60 years of age, inclusive.
- Resides in a stable living situation, according to the investigator's judgment.
- 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.
- No more than moderate clinical symptom burden severity, as defined by the following: Montgomery Asberg Depression Rating Scale < 20 Young Mania Rating Scale <12
Key exclusion criteria (13 listed)
- Failure to perform screening or baseline examinations
- Hospitalization within 8 weeks before screening, or change in mood stabilizing or antidepressant medication or dose within 2 months prior to screening.
- Individuals who have participated in another clinical study within the past 2 months.
- Individuals with tardive dyskinesia.
- Individuals with other DSM-V Axis I or Axis II primary diagnoses.
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 |
|---|---|---|
| JNJ-18038683JNJ-18038683 10-20 mg/day tablet for 8 weeks | Drug | JNJ-18038683 |
| Placeboplacebo tablet daily | Drug | Placebo |
Primary outcome
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
2 secondary outcomes
Montgomery-Asberg Depression Rating Scale
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39250138Arshadi M, Elmaadawi AZ, Nasr S, Jayathilake K, Rassnick S, Ford L, Drevets WC, Meltzer HY. Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder. J Clin Psychopharmacol. 2024 Sep-Oct 01;44(5):481-491. doi: 10.1097/JCP.0000000000001889.
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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.
Herbert Y Meltzer, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing JNJ-18038683 in people with Bipolar Disorder, run by Herbert Meltzer at 1 site 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 18 inclusion and 13 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 14 Nov 2023. 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 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?
Yes. Results are posted in the registry (first posted 3 Jul 2023). 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?
The 8-week Evaluation of Verbal Fluency Performance After Randomization (time frame: Baseline and week 8). 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 NCT02466685, which also lists 1 linked publication.
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 14 Nov 2023.