ATP - Antidepressant Trial with P2X7 Antagonist JNJ-54175446
Research type
Research Study
Full 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.
IRAS ID
248987
Contact name
Professor Edward T. Bullmore
Contact email
Sponsor organisation
Cambridgeshire and Peterborough NHS Foundation Trust and University of Cambridge
Eudract number
2018-001884-21
Duration of Study in the UK
3 years, 3 months, 9 days
Research summary
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 we aim 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.
We 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 MRI brain scans at different visits throughout the trial. The trial will be carried out across 5 centres in the UK.REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
19/EE/0035
Date of REC Opinion
4 Jun 2019
REC opinion
Further Information Favourable Opinion