Imaging 5HT7 Antagonist Effects in Bipolar Disorder

NCT03633357 | Unknown

• 1 other identifier: 240244
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The main aim of this research is to examine the potential of 5HT7 antagonists for the treatment of cognitive impairment in bipolar disorder by determining the effect of the 5HT7 antagonist JNJ-18038683 on cognitive and emotional processing related brain activity in cognitively impaired people with bipolar disorder and healthy participants using functional MRI (fMRI). This study is designed to contribute to the rational validation of 5HT7 antagonists as a treatment for cognitive impairment in bipolar disorder and to support the development of clinical trials and further drug development in this area. The study will also examine the effect of 5HT7 antagonism on brain function in healthy participants as this has never been investigated before, and to use as a comparator to determine whether 5HT7 antagonism effects disease specific impairments in task related brain activity and cerebral blood flow.

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder; Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

• fMRI imaging

  Change in cognitive task related right superior frontal gyrus and dorsolateral prefrontal cortex brain activations associated with JNJ-18038683 treatment.

  after 7 days on either placebo or JNJ-18038683

• ISBD-BANC

  Change in cognitive performance, as measured by change in International Society for Bipolar Disorders Battery for the Assessment of Cognition (ISBD-BANC) test battery composite score, associated with JNJ-18038683 treatment

  after 7 days on either placebo or JNJ-18038683

Secondary Outcomes (4)

• fMRI imaging

  7 days

• fMRI imaging

  7 days

• QIDS-CR - Quick Inventory of Depression Symptomology

  7 days

• YMRS - Young Mania Rating Scale

  7 days

Study Arms (2)

JNJ-18038683 first

EXPERIMENTAL

One week of JNJ-18038683, followed by one week of Placebo after a two week-washout period,

Drug: JNJ-18038683; Drug: Placebo

Placebo first

PLACEBO COMPARATOR

One week of Placebo followed by one week of JNJ-18038683 after a two week-washout period,

Drug: JNJ-18038683; Drug: Placebo

Interventions

JNJ-18038683 DRUG

JNJ-18038683 has been developed by Janssen Pharmaceuticals (Johnson and Johnson), and is a relatively selective high affinity functional 5-HT7 receptor antagonist. Participants will take two 10-mg tablets daily, for seven days.

JNJ-18038683 first; Placebo first

Placebo DRUG

Participants will take two placebo tablets daily, for seven days.

JNJ-18038683 first; Placebo first

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Right-handed participants between the ages of 18 and 60 years, inclusive, who are currently in a euthymic mood state defined as ≤8 on the Hamilton Rating Scale for Depression (HAM-D) and Young Mania Rating Scale (YMRS).
• The participant has a resting pulse ≥51 bpm and ≤100 bpm.
• The subject has a resting systolic blood pressure ≥91 mmHg and ≤140 mmHg and a resting diastolic blood pressure ≥51 mmHg and ≤90 mmHg at the Screening Visit. An out-of-range resting systolic blood pressure may be repeated if a medically valid reason is present, for example, the subject suffers from white-coat hypertension or experienced stress (e.g. late arrival).The medically valid reason must be documented and signed by the investigator.
• The subject has clinical laboratory test values within the reference ranges based on the blood and urine samples taken at the Screening Visit. Borderline value parameters may be accepted if they are, in the opinion of the investigator, clinically insignificant.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• Ability to understand written and verbal instructions in English.
• Women of child bearing potential must have a negative pregnancy test at screening and at baseline visits and must agree to use a medically accepted method of contraception throughout the study.

You may not qualify if:

• Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing), and any primary psychiatric diagnosis other than bipolar disorder.
• Participants who have used or plan to use during the conduct of the study:
• Fluoxetine within 5 weeks prior to the baseline visit or during the study
• Monoamine oxidase inhibitors within 3 weeks of the baseline visit or during the study
• Other prescription medication within 7 days prior to the baseline visit or within or 5 half-lives (whichever is longer) with the exception of the following which are allowed:
• ii. Limited use (not more than 3 days per week) medications (non CYP2D6 or CYP2C19 substrates) such as prn treatments for asthma or acute migraine.
• iii. Women who are taking hormone replacement therapy or hormonal contraception must be on a stable regimen for 30 days prior to screening and remain on that regimen throughout the study
• iv. Paracetamol may be used at doses of 1 g/day
• Herbal supplements must be discontinued 28 days prior to the first dose of study medications. At the discretion of the investigator a shorter drug free or discontinuation period may be acceptable depending on the precise drugs/supplements taken.
• Currently taking medications with significant 5HT7 antagonist properties (eg lurasidone, vortioxetine)
• Treatment with another experimental medicine drug within the 3 months preceding the first dose of study medication, over the course of the study, and two weeks after discontinuing study medications
• History of sensitivity to JNJ-18038683 or other medications with 5HT7 antagonist properties.
• History of febrile illness within 5 days prior to the first dose.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• lead ECG considered abnormal by a clinician

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

King's College London

London, SE5 8AF, United Kingdom

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder; Cognitive Dysfunction

Interventions

3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydro-1-(phenylmethyl)pyrazolo(3,4-d)azepine 2-hydroxy-1,2,3-propanetricarboxylate

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Officials

• Paul Stokes, PhD

  King's College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Gottlieb, PhD

CONTACT

+447725 179208; natalie.n.gottlieb@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Crossover, Mechanistic Pharmacological Neuroimaging Study

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 16, 2018
• Study Start: August 16, 2018
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: September 8, 2021

Record last verified: 2021-09

Locations

GB (1)