NCT03633357Unknown不适用
Translational Validation of 5HT7 Antagonists as a Treatment for Cognitive Impairment in Bipolar Disorder: a Proof of Principle Neuroimaging Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- fMRI imaging
研究概览
简要总结
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.
详细描述
OBJECTIVE
Primary:
To determine the effect of 5HT7 antagonism on cognition related brain activations and cognitive performance in people with bipolar disorder.
Secondary:
To examine the effect of 5HT7 antagonism on emotional processing related brain activations in people with bipolar disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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:
- •i. For the bipolar disorder group, prescribed psychotropic medications as long as they are not included in the list of CYP2D6 and CYP2C19 medications listed in exclusion's 3 and 4 below.
- •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.
- •As JNJ-18038683 is a strong inhibitor of cytochrome P450 2D6, use of the following CYP2D6 substrates will be an exclusion: carvedilol, S-metoprolol, propafenone, timolol, amitriptyline, clomipramine, desipramine, fluoxetine, imipramine, paroxetine, venlafaxine, haloperidol, perphenazine, risperidone, thioridazine, zuclopenthixol, alprenolol, amphetamine, aripiprazole, atomoxetine, bufuralol, chlorpheniramine, chlorpromazine, clonidine, codeine, debrisoquine, dexflenfluramine, dextromethorphan, donepezil, duloxetine, encainide, flecainide, fluvoxamine, lidocaine, metoclopramide, methoxyamphetamine, mexilletine, minaprine, nebivolol, nortriptyline, ondansetron, oxycodone, perhexiline, phenacetin, phenformin, promethazine, propafenone, propranolol, sparteine, tamoxifen, tramadol, venlafaxine. Participants planning to use these medications after their participation in the study must commit to a two-week washout period at the end of the study before commencing these medications.
- •As JNJ-18038683 is a moderate inhibitor of cytochrome P450 2C19, use of the following CYP2C19 substrates will be an exclusion: Proton pump inhibitors, phenytoin, phenobarbitone, diazepam, Norphenytoin, S-mephenytoin, phenobarbitone, amitriptyline, carisoprodol, citalopram, chloramphenicol, clomipramine, clopidogrel, cyclophosphamide, hexobarbital, imipramine, indomethacin, labetalol, R-mephobarbital, moclobemide, nelfinavir, nilutamide, primidone, progesterone, proguanil, propranolol, teniposide, warfarin, voriconazole. Participants planning to use these medications after their participation in the study must commit to a two-week washout period at the end of the study before commencing these medications.
- •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).
- •12-lead ECG considered abnormal by a clinician
- •A positive urine drug screen on or after the screening visit during their active involvement in the study for opiates, methadone, cocaine, amphetamines (including MDMA), barbiturates, benzodiazepines and cannabinoids.
- •Unwilling or unable to comply with the Lifestyle guidelines.
- •Participants who, in the opinion of the investigator, have any medical or psychological condition or social circumstances which would impair their ability to participate reliably in the study, or who may increase the risk to themselves or others by participating.
- •Diagnosis of alcohol or drug dependence in the year prior to recruitment or diagnosis of harmful use of alcohol or drugs within the previous 6 months.
- •Female participants of child bearing potential who are not using adequate contraception as specified in above criteria for inclusion.
- •Female participants that are currently pregnant or are breast feeding.
- •A history of moderate to severe head injury or neurological conditions that may impair cognitive performance
- •Ineligibility to undergo MRI imaging, for example the presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire.
- •Participant weight in excess of 126kg or physical dimensions such that the participant may not fit in the MRI scanner.
- •A history of claustrophobia or participant feels unable to lie in a MRI scanner for a period of around one hour.
- •Additional exclusion criteria for participants with bipolar disorder
- •Significant change in dose or type of prescribed psychotropic medications in the month prior to the Screening visit or likely change during the study.
- •Additional exclusion criteria for healthy participants
- •A personal history of any significant psychiatric disorder including a history of suicide attempts or significant suicidal ideation or a family history of severe mental illness (such as psychosis, bipolar disorder or schizophrenia).
研究组 & 干预措施
JNJ-18038683 first
Experimental
One week of JNJ-18038683, followed by one week of Placebo after a two week-washout period,
干预措施: JNJ-18038683 (Drug)
JNJ-18038683 first
Experimental
One week of JNJ-18038683, followed by one week of Placebo after a two week-washout period,
干预措施: Placebo (Drug)
Placebo first
Placebo Comparator
One week of Placebo followed by one week of JNJ-18038683 after a two week-washout period,
干预措施: JNJ-18038683 (Drug)
Placebo first
Placebo Comparator
One week of Placebo followed by one week of JNJ-18038683 after a two week-washout period,
干预措施: Placebo (Drug)
结局指标
主要结局
fMRI imaging
时间窗: after 7 days on either placebo or JNJ-18038683
Change in cognitive task related right superior frontal gyrus and dorsolateral prefrontal cortex brain activations associated with JNJ-18038683 treatment.
ISBD-BANC
时间窗: after 7 days on either placebo or JNJ-18038683
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
次要结局
- fMRI imaging(7 days)
- QIDS-CR - Quick Inventory of Depression Symptomology(7 days)
- YMRS - Young Mania Rating Scale(7 days)
研究者
研究点 (1)
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