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Report for Clinical Trial NCT02362529

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder

The purpose of this study is to determine if translocator protein total distribution volume (TSPO VT) is elevated in major depressive disorder that is not responding to medication and if adding minocycline can affect TSPO VT. Many remain treatment resistant with common antidepressant treatments and the investigators think it may be due to poor targeting of brain pathologies.

NCT02362529 Major Depressive Disorder
MeSH:Depressive Disorder Depression Depressive Disorder, Major
HPO:Depressivity

3 Interventions

Name: Minocycline

Description: 50 mg and 100 mg capsule, oral administration
Type: Drug
Group Labels: 1

Minocycline

Name: Placebo

Description: Lactose monohydrate in identical gel capsules to minocycline, oral administration.
Type: Drug
Group Labels: 1

Placebo

Name: Celecoxib

Description: 100 mg and 200 mg capsules, oral administration.
Type: Drug
Group Labels: 1

Celecoxib


Primary Outcomes

Description: TSPO VT will be measured using [18F]FEPPA positron emission tomography brain scans. Eligible MDE participants will be randomized to either minocycline or placebo. Following 8 weeks of either minocycline or placebo treatment, MDE participants will have a second PET scan .

Measure: Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects

Time: Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans

Description: Compare baseline TSPO VT prior to treatment between MDE group and healthy group

Measure: Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects

Time: Pre-treatment scan will take place up to 8 weeks from initial assessment

Secondary Outcomes

Description: Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.

Measure: Change in Hamilton Depression Rating Scale Score

Time: Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment).

Other Outcomes

Description: To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.

Measure: Hopkins Verbal Learning Test-Revised

Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

Description: To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.

Measure: Brief Visuospatial Memory Test-Revised

Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

Description: To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.

Measure: Comprehensive Trails Making Test

Time: Pre- and post-minocycline or placebo treatment.

Description: The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA. The genetic sample will also be used to study sequences of genes that are believed to affect TSPO expression, inflammation, mood and conditions that may predispose to mood disorders.

Measure: Genetic sample

Time: Phase 1-single sample

Description: Analyses will include complete blood cell count (CBC), ESR, hepatic and renal function. Peripheral marker analyses will include proteins related to TSPO expression and inflammation. Plasma minocycline and celecoxib levels will be analyzed.

Measure: Blood samples (serum and plasma)

Time: Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).

Purpose: Basic Science

Allocation: Randomized

Single Group Assignment


There is one SNP

SNPs


1 rs6971

The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA.



HPO Nodes


HPO:
HP:0000716: Depressivity
Genes 381
TRNF ARSG FUS ANG PDE11A GLE1 SARS1 PLA2G6 NEK1 SLC18A2 HLA-DRB1 FMN2 TRNS2 XK SMPD1 HTT CHD7 ATXN10 SNCAIP TCF4 ATP1A3 GPR101 DRD2 PDGFB OPTN TWNK RRM2B GBA KCNT1 BCR JPH3 NOTCH3 PDCD1 PAH PIGC HTR2A PRKN DNMT1 TRNL1 ZC3H14 ST3GAL3 USH1G LMNB1 LIMK1 SNCA ADH1C ATRX OCRL PRKACA TBL2 FMR1 PRNP CPOX USP8 PPARGC1A UCHL1 VPS13C GLUD2 KCNJ2 TBK1 MST1 TWNK MSTO1 MAPT B3GALNT2 PPP2R2B PROKR2 PRNP XPR1 RPS20 POLG SQSTM1 ARMC5 NDST1 TRNN TARDBP USH2A TRNL2 GNAS DCPS STX16 TTC19 ATXN10 SLC20A2 TBX1 CSF1R GSN ND1 ATP7B CDH23 TAC3 MYO7A WFS1 TWNK PDGFRB HS6ST1 PRKCG ESPN COX2 HIRA GNAS CLCN4 CASR ARSA GABRA1 GCH1 DNA2 MAPT UBQLN2 GDAP2 FGF8 TOR1A SEMA4A TK2 UFD1 FUS DGUOK EPM2A HARS1 C9ORF72 POLG UNC13A PODXL TBK1 LRRK2 CLIP2 HTRA2 DCTN1 TRAPPC9 C19ORF12 PLA2G6 MATR3 C12ORF4 GRIK2 SLC6A4 PRNP MECP2 CP HLA-DQB1 CFAP410 CACNA1G MED23 AARS2 VCP TRNQ PRNP JMJD1C SRPX2 VAPB MYO7A SGCE CC2D1A VPS35 ABCA7 CCNF EHMT1 C9ORF72 SNCA MLH1 PANK2 DUSP6 CEP78 GABRB3 FIG4 NR4A2 BMPR1A PTPN22 PARK7 MECP2 DNMT1 WASHC4 TRNS1 CACNA1G AMACR VCP ALMS1 IDUA CHMP2B PMS1 GIGYF2 KISS1R TSC1 RPS6KA3 COQ2 ERBB4 KDM5B POLG2 SEC24C SLC2A1 COQ2 DNAJC13 MSTO1 MSH6 FBXO31 RRM2B CHMP2B HTT POLG EDC3 PGAP1 NSMF SLC25A4 ATXN2 PIK3CA THOC2 PER2 GLA CACNA1H TBC1D7 PAH SQSTM1 POLG GNAS PRNP AIMP1 ARMC5 CIB2 LINS1 GABRG2 FGFR1 C9ORF72 CDH23 METTL23 TACR3 EPCAM TRNS1 PPOX KRAS ANOS1 SLC45A1 WARS2 POLG FA2H COASY HLA-DQB1 GNAS TRNL1 PRSS12 CLN6 GBA PMS2 C9ORF72 CLCN4 HBB TSC2 PDGFB AIP PRKAR1A COMT MAPT DNAJC5 CRADD ATXN8 ATXN2 ATP13A2 ARVCF GTF2I WHRN GBA TRNW COX3 KISS1 TREM2 TGFBR2 PDZD7 AFG3L2 PDGFRB BCS1L MAN1B1 SNCA VCP NEFH TRNH COX1 ATP1A3 DAO CPOX PINK1 LRRK2 HMBS CRBN DCTN1 CTSF GPR35 CLIP1 TBX1 ND5 TAF15 ND4 PTS PON3 MED25 DNAJC6 TRNS2 NSUN2 FMO3 SPAST HMBS FGF17 ELN PON1 CBS CYP27A1 FGF14 PSAP FMR1 TMEM106B KCTD17 RREB1 CHCHD10 TWNK TBP AP2S1 ATXN8OS FRRS1L ATXN8OS BAZ1B HNMT FAN1 ADGRV1 PINK1 HNRNPA1 PRPH TUSC3 MBOAT7 PRNP PANK2 FGF14 GABRG2 KCTD17 PDGFRB TECR LMAN2L EIF4G1 GNAS CLRN1 EPHA4 GP1BB JRK IQSEC1 TREM2 MSH2 PSEN1 RFC2 PON2 MAPK1 SGCE PER3 PROK2 GRIN2A TNIK PFN1 MLH3 GRN ND6 CRKL ANXA11 C9ORF72 GNRHR EZR VCP USH1C GNRH1 TOR1A WFS1 POLG NHLRC1 CISD2 CHCHD10 WDR11 SPRY4 PPT1 PCDH15 TBP GTF2IRD1 SOD1 RSRC1 GLT8D1 DCTN1 GNA11 TARDBP
Protein Mutations 4
A1298C C677T V158M V66M