SNPMiner Trials by Shray Alag


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Report for SNP rs1653624

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 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

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

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.

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

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: 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.

Measure: Change in scores on SHAPS

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: 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).

Measure: Change in scores on CFQ

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: 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.

Measure: Change in scores on QIDS-SR16

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: 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.

Measure: Change in scores on GAD-7

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: 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.

Measure: Change in score on participant self-reported depression scale

Time: At baseline and at 8 weeks of treatment

Description: 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.

Measure: Change in scores in the cognitive function test ReVeRe-D

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: The continuous performance test is a computerised test of sustained attention which provides a measure of cognitive fatigue.

Measure: Change in scores in Continuous performance test

Time: At baseline, 2, 5 and 8 weeks of treatment

Description: 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.

Measure: Change in scores in Emotional Test battery

Time: At baseline and 2 weeks of treatment

Description: Brain structure and function will be assessed using fMRI/MRI

Measure: Change in Brain structure and function

Time: Baseline and at 8 weeks fo treatment

Description: Heart rate variability will be measured for 15 minutes during rest and whilst completing one of the cognitive tasks.

Measure: Change in heart rate variability

Time: Baseline and at 8 weeks fo treatment

Other Outcomes

Description: 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.

Measure: Change in Salivary cortisol levels as a measure of biological stress

Time: Samples collected within 7 days prior to Baseline visit and within 7 days prior to visit 4

Description: 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.

Measure: Measurement of peripheral blood peripheral cytokine and chemokine levels

Time: Baseline and at 8 weeks fo treatment

Description: The immune cellular content of the blood samples will be analysed with mass cytometry using the commercial kit Maxpar® Direct™ Immune Profiling Assay.

Measure: Measurement of peripheral blood immunophenotypes

Time: Baseline and at 8 weeks fo treatment


HPO Nodes


HP:0000716: Depressivity
Genes 390
PDGFRB PFN1 DNAJC13 LIMK1 TRNS1 HTT LMAN2L CLN6 TSC2 FMR1 PSAP FGFR1 CPOX GBA GNAS DRD2 EPCAM NOTCH3 KISS1 ELN GABRG2 CLRN1 PON1 AARS2 PINK1 TBP ATRX RRM2B MAPT GPR35 UCHL1 PSEN1 SPRY4 PPARGC1A TACR3 FGF17 GNA11 C19ORF12 SNCA CP GLA HLA-DRB1 CHMP2B KCTD17 ND4 PDGFB MLH3 MSH2 NR4A2 USH2A ATP1A3 GIGYF2 PRNP TCF4 USH1C TRNQ DNMT1 RUNX1 HLA-DQB1 NEK1 ZC3H14 CLIP1 CACNA1G PDGFRB COQ2 TOR1A POLG GNAS OPTN MECP2 MAN2B1 GABRG2 C9ORF72 UNC13A GNRHR COX3 WDR11 GRN KCNT1 FMR1 ARVCF FBXO31 VPS13C MED25 SQSTM1 SLC6A4 MST1 MAPK1 MAPT MBOAT7 TRAPPC9 GBA ARSA ERBB4 UBQLN2 WFS1 MED23 SLC18A2 SQSTM1 PRNP ARMC5 TBP OCRL ATXN8OS TRNS1 USH1G ADGRV1 HS6ST1 GNAS GTF2IRD1 UFD1 TWNK TRNH C9ORF72 CCNF SGCE MAPT TARDBP RFC2 PLA2G6 TTC19 POLG XPR1 SNCAIP LRRK2 PRKCG DCTN1 PDGFRB PROKR2 TREM2 CLIP2 COMT GABRA1 XK TBC1D7 DNMT1 PRKACA JMJD1C NEFH SOD1 FRRS1L TRNL2 PRSS12 KDM5B DMPK CEP78 HIRA PPOX BCR VCP TARDBP EPM2A DNAJC5 COX1 PGAP1 MSH6 PMS1 MAN1B1 ND5 PRKAR1A RSRC1 DUSP6 HBB ST3GAL3 IQSEC1 CISD2 GSN ND6 EHMT1 TOR1A POLG ALMS1 LMNB1 CHD7 STX16 PRNP CHMP2B CFAP410 BCS1L PER3 TK2 TBX1 TUSC3 FA2H RPS20 AIMP1 FGF14 COX2 TREM2 DNA2 CLCN4 CPOX EDC3 CRBN GDAP2 SEC24C PAH FLT4 EPHA4 TMEM106B FGF8 EIF4G1 NSMF SLC2A1 AMACR SLC25A4 TRNL1 KISS1R FGF14 PAH RRM2B CBL ATP13A2 CHCHD10 DAO ATXN10 ADH1C CRADD PDGFB PMS2 TRNF PON2 LINS1 SYNJ1 ATXN8OS FUS PLA2G6 AP2S1 HNRNPA1 MSTO1 SNCA CACNA1H ND1 RREB1 PROK2 MYO7A SLC45A1 FUS JPH3 PODXL GLE1 SGCE GPR101 SPAST MATR3 MAN2B1 PON3 WHRN PRNP COASY PDCD1 LRRK2 GBA DCPS PDZD7 GNAS PPT1 COQ2 AIP GLT8D1 TGFBR2 MYO7A SMPD1 WFS1 PIGC KCNJ2 TWNK ANOS1 HTR2A POLG ATXN8 ABCA7 SARS1 AFG3L2 ANXA11 POLG PTPN22 RPS6KA3 SEMA4A TWNK PARK7 CC2D1A POLG2 GCH1 DGUOK HTRA2 BAZ1B TRNS2 TAF15 VPS35 ASXL1 ATXN2 HTT C12ORF4 CDH23 PCDH15 GP1BB PANK2 CACNA1G EZR HARS1 PIK3CA FAN1 FMO3 ATP1A3 MSTO1 NSUN2 PANK2 ARSG TNIK PINK1 PER2 TET3 TWNK SNCA CSF1R CLCN4 VCP GRIK2 GTF2I BMPR1A ATXN2 TET2 TBK1 TAC3 TRNN TBK1 FMN2 ATP7B SRPX2 THOC2 CRKL GRIN2A PTS VCP FIG4 NHLRC1 ARMC5 PRPH CDH23 TRNL1 CTSF ATXN10 TRNW JRK C9ORF72 CHCHD10 TBX1 GABRB3 CASR MLH1 PRKN SRSF2 CYP27A1 KRAS DCTN1 B3GALNT2 NDST1 PRNP HNMT HLA-DQB1 ANG TSC1 VAPB SLC20A2 METTL23 WASHC4 TBL2 CIB2 HMBS HMBS C9ORF72 DCTN1 PPP2R2B KCTD17 ESPN VCP POLG C9ORF72 PDE11A CBS GNRH1 PRNP TECR IDUA GNAS TRNS2 USP8 GLUD2 DNAJC6
Protein Mutations 4
A1298C C677T V158M V66M