NLP SNP

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.

NCT04116606 Depressive Disorder, Major Inflammation Drug: Active JNJ-54175446 Drug: Placebo

MeSH:Inflammation Depressive Disorder Depression Depressive Disorder, Major

HPO:Depressivity

3. Presence of two copies of the loss-of-function C allele at rs3751143, and/or has one copy of the loss-of-function A allele at rs1653624 in the P2RX7 gene.

Primary Outcomes

Description: 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. (Visit 4)

Measure: Change from baseline in total score on the MADRS scale at week 8

Time: At baseline and at 8 weeks of treatment

Secondary Outcomes

Measure: Change from baseline in total score on the MADRS scale

Time: At baseline, 2 and 5 weeks of treatment

Description: 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.

Measure: Change in scores on Perceived Stress Scale