Antidepressant Trial With P2X7 Antagonist JNJ-54175446 (ATP)
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|ClinicalTrials.gov Identifier: NCT04116606|
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Depression is one of the most important causes of disability in the world today, with major personal, social and economic costs. Although some moderately effective drug treatments are already available, about a third of patients with major depressive disorder (MDD) remain depressed despite current treatment.
There is growing evidence that inflammation - the response of the body's immune system to physical and social stresses - can cause depressive symptoms in some patients. It is therefore predicted that anti-inflammatory drugs could have anti-depressant effects and the research team aims to test this using a new drug, JNJ-54175446, which blocks the activity of a receptor called P2X7. P2X7 is present on many immune cells and plays a key role in the release of inflammatory molecules during stress, which may be linked to stress-related depression.
The research team will recruit approximately up to 142 participants with MDD to this clinical trial. Patients will have moderate-severe depressive symptoms despite ongoing treatment with a conventional anti-depressant drug, and they will have blood test results at screening that indicate they are likely to have active P2X7 signalling in the brain. Eligible participants will be randomly allocated to receive either 50mg/day JNJ-54175446 or placebo for 8 weeks. Participants will be assessed at weeks 2, 5 and 8 using a standard clinical depression scale and the scores compared between those treated with placebo and those treated with JNJ-54175446. To understand more about the effects of JNJ-54175446 on the immune system and the brain, patients will also complete additional blood tests, questionnaires and magnetic resonance imaging (MRI) brain scans at different visits throughout the trial. The trial will be carried out across 5 centres in the UK.
|Condition or disease||Intervention/treatment||Phase|
|Depressive Disorder, Major Inflammation||Drug: Active JNJ-54175446 Drug: Placebo||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||142 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomised, Placebo-controlled, Double-blind Trial of the Antidepressant Efficacy of a Novel CNS-penetrant P2X7 Receptor Antagonist, JNJ-54175446, in People With Major Depressive Disorder, an Incomplete Response to Monoaminergic Antidepressant Drugs, and a Biomarker Profile Predictive of Active P2X7 Signalling|
|Actual Study Start Date :||September 12, 2019|
|Estimated Primary Completion Date :||May 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Active Comparator: Active JNJ-54175446
JNJ-54175446 is an unlicensed drug currently being developed by Janssen Pharmaceuticals. The drug is presented in oral capsules, each capsule containing 50 mg of JNJ-54175446. Participants will be asked to self-administer one capsule daily for 8 weeks.
Drug: Active JNJ-54175446
JNJ-54175446 is a novel, potent, selective, and brain-penetrant antagonist of the adenosine triphosphate (ATP)-gated P2X7 channel.
|Placebo Comparator: Matching placebo||
Matching placebo containing the same excipients
- Change from baseline in total score on the MADRS scale at week 8 [ Time Frame: At baseline and at 8 weeks of treatment ]
The Montgomery Asberg Depression Rating Scale (MADRS), a researcher-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
- Change from baseline in total score on the MADRS scale [ Time Frame: At baseline, 2 and 5 weeks of treatment ]The Montgomery Asberg Depression Rating Scale (MADRS), a researcher-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
- Change in scores on Perceived Stress Scale [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]Perceived Stress Scale is a questionnaire measure of recent or current social stress. This scale ranges from 0 to 40; scores ranging from 0-13 would be considered low stress; scores ranging from 14-26 would be considered moderate stress; scores ranging from 27-40 would be considered high perceived stress.
- Change in scores on SHAPS [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]Snaith-Hamilton Pleasure Scale. SHAPS is an instrument developed for the assessment of hedonic capacity and consists of 14-items. Four major domains are covered in the scale, namely interest/pastimes, social interaction, sensory experience, and food/drink. The score range is 0-14. The higher the score the lower the ability to experience pleasure of the patient.
- Change in scores on CFQ [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]Chalder Fatigue Questionnaire (CFQ). The Fatigue Scale, sometimes referred to as the Chalder Fatigue Questionnaire, is a self-administered questionnaire for measuring the extent and severity of fatigue within both clinical and non-clinical, epidemiological populations. The respondent's global score can range from 0 to 33. The global score also spans two dimensions—physical fatigue (measured by items 1-7) and psychological fatigue (measured by items 8-11).
- Change in scores on QIDS-SR16 [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]Quick Inventory of Depressive Symptomatology (QIDS-SR16). The QIDS-SR16 is designed to assess the severity of depressive symptoms and is sensitive to change due to with medications, psychotherapy, or other treatments. Participants will provide responses to each item of this instrument with a 4-point Likert scale, with scores ranging from 0-3 for each item. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1 to 5, mild 6 to 10, moderate 11 to 15, severe 16 to 20 and very severe 21 to 27.
- Change in scores on GAD-7 [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]Generalized Anxiety Disorder 7 (GAD-7). GAD-7 is a self-reported questionnaire for screening and severity measuring of GAD. GAD-7 has seven items, which measure severity of various signs of GAD according to reported response categories with assigned points. Assessment is indicated by the total score, which made up by adding together the scores for all 7 items. The score ranges from 0 to 21. Using a scale of severity of anxiety of none, mild, moderate and severe, corresponding to GAD-7 total scores are none 0 to 4, mild 5 to 9, moderate 10 to 14 and severe 15 to 21.
- Change in score on participant self-reported depression scale [ Time Frame: At baseline and at 8 weeks of treatment ]Participants will be asked to self-assess their depression using the Beck Depression Inventory scale (BDI). BDI is a 21-question multiple-choice self-report inventory, widely used for assessment of depression, including in the NIMA BIODEP study, with a score range of 0-63. Each of the 21 items is rated by the participant on a 4 point scale.
- Change in scores in the cognitive function test ReVeRe-D [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]Revere-D is an application developed by Johnson and Johnson, and consists of a battery of eight validated cognitive tasks that assesses cognitive functions, such as memory and learning, that do not involve cognitive processing of emotionally salient stimuli.
- Change in scores in Continuous performance test [ Time Frame: At baseline, 2, 5 and 8 weeks of treatment ]The continuous performance test is a computerised test of sustained attention which provides a measure of cognitive fatigue.
- Change in scores in Emotional Test battery [ Time Frame: At baseline and 2 weeks of treatment ]The emotional test battery will consist of 3 validated computerised tasks which are used to assess cognitive functions that involve processing emotionally salient stimuli, such as human faces expressing emotional states.
- Change in Salivary cortisol levels as a measure of biological stress [ Time Frame: Samples collected within 7 days prior to Baseline visit and within 7 days prior to visit 4 ]Participants will be asked to provide saliva samples before treatment commencement and during the last week of treatment in order for the cortisol levels to be analysed.
- Change in Brain structure and function [ Time Frame: Baseline and at 8 weeks fo treatment ]Brain structure and function will be assessed using fMRI/MRI
- Change in heart rate variability [ Time Frame: Baseline and at 8 weeks fo treatment ]Heart rate variability will be measured for 15 minutes during rest and whilst completing one of the cognitive tasks.
- Measurement of peripheral blood peripheral cytokine and chemokine levels [ Time Frame: Baseline and at 8 weeks fo treatment ]Blood samples will be collected for the analysis of cytokine and chemokine levels with a multiplex immunoassay using the MSD Multi-spot assay system with the Cytokine Panel 1, Proinflammatory panel 1 and Chemokine panel 1 kits providing concentration of all analytes of the panel in pg/ml.
- Measurement of peripheral blood immunophenotypes [ Time Frame: Baseline and at 8 weeks fo treatment ]The immune cellular content of the blood samples will be analysed with mass cytometry using the commercial kit Maxpar® Direct™ Immune Profiling Assay.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04116606
|Contact: Elizabeth Chong||01223 firstname.lastname@example.org|
|Contact: CCTU Core||01223 email@example.com|
|Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ|
|Contact: Ciara O'Donnell 01223 465221 firstname.lastname@example.org|
|Principal Investigator: David Christmas|
|Cardiff University Brain Research Imaging Centre||Not yet recruiting|
|Cardiff, United Kingdom, CF24 4HQ|
|Contact: Caroline Young ATPTrial@cardiff.ac.uk|
|Principal Investigator: Neil Harrison|
|Queen Elizabeth University Hospital||Not yet recruiting|
|Glasgow, United Kingdom, G3 8SW|
|Contact: Murray Sutherland 0141 232 7600|
|Principal Investigator: Nagore Penades|
|The Maurice Wohl Clinical Neuroscience Institute||Not yet recruiting|
|London, United Kingdom, SE5 9RT|
|Contact: Courtney Worrell 0207 8485440 email@example.com|
|Principal Investigator: Maria Antonietta|
|Warneford Hospital||Not yet recruiting|
|Oxford, United Kingdom, OX3 7JX|
|Contact: Alanna Sheldon-Battle 01865 902135 firstname.lastname@example.org|
|Principal Investigator: Phil Cowen|
|Principal Investigator:||Edward Bullmore||Cambridgeshire and Peterborough NHS Foundation Trust|