SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03549689

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Effect of Reducing Nucleotide Exposure on Bone Health (ReNew)

This is an open-label, randomized pilot study to assess the effect on bone mineral density (BMD) of a switch from a tenofovir alafenamide-containing antiretroviral regimen to dolutegravir/lamivudine vs. a continuation of the tenofovir alafenamide-containing regimen.

NCT03549689 HIV/AIDS HIV-1-infection Osteopenia
MeSH: Bone Diseases, Metabolic
HPO: Osteopenia

2 Interventions

Name: Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC)

Description: Participants randomized to the Switch Arm will take DTG 50mg/3TC 300mg FDC once daily with or without food at approximately the same time each day.

Type: Drug

Switch

Name: Current tenofovir alafenamide (TAF)-containing ART regimen

Description: Continuation of current TAF-containing ART for 96 weeks.

Type: Drug

Continuation


Primary Outcomes

Description: Compare the percentage change from entry to 96 weeks in lumbar spine BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

Measure: Percent change in lumbar spine Bone Mineral Density (BMD) at 96 weeks

Time: Baseline and 96 weeks

Secondary Outcomes

Description: Compare the percentage change from entry to 48 weeks in lumbar spine BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

Measure: Percentage change in lumbar spine BMD at 48 weeks

Time: Baseline and 48 weeks

Description: Compare the percentage change from entry to 48 weeks in total hip BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

Measure: Percentage change in total hip BMD at 48 weeks

Time: Baseline, 48 weeks

Description: Compare the percentage change from entry to 96 weeks in total hip BMD in those randomized to DTG/3TC vs. those continuing a TAF-based regimen

Measure: Percentage change in total hip BMD at 96 weeks

Time: Baseline, 96 weeks

Description: Compare the changes in CTX from entry to 12, 48, and 96 weeks

Measure: Change in CTX (a bone resorption marker)

Time: Baseline, 12 weeks, 48 weeks, and 96 weeks

Description: Compare the changes in P1NP from entry to 12, 48, and 96 weeks

Measure: Change in P1NP (a bone deposition marker)

Time: Baseline, 12 weeks, 48 weeks, and 96 weeks

Description: Compare the changes in urine β2-microglobulin from entry to 48 weeks and 96 weeks.

Measure: Change in urine β2-microglobulin (renal tubular marker)

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the changes in RBP from entry to 48 weeks and 96 weeks.

Measure: Change in urine RBP (renal tubular marker)

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the changes in protein from entry to 48 weeks and 96 weeks.

Measure: Change in urine protein

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the changes in urine albumin from entry to 48 weeks and 96 weeks.

Measure: Change in urine albumin

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the changes in fractional excretion of phosphate from entry to 48 weeks and 96 weeks.

Measure: Change in fractional excretion in phosphate

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the percentage change from entry to 48 weeks and 96 weeks in total lean mass (as measured by whole body DXA)

Measure: Percentage change in total lean mass

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the percentage change from entry to 48 weeks and 96 weeks in trunk fat (as measured by whole body DXA)

Measure: Percentage change in trunk fat

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the percentage change from entry to 48 weeks and 96 weeks in limb fat (as measured by DXA)

Measure: Percentage change in limb fat

Time: Baseline, 48 weeks, and 96 weeks

Description: Compare the levels of HIV RNA <50 copies/mL and below the limit of quantification (BLQ) at 48 weeks and 96 weeks using the FDA snapshot algorithm

Measure: Maintenance of HIV RNA level

Time: 48 weeks and 96 weeks

Description: Compare rates of grade 3 or 4 adverse events experienced by participants through 96 weeks

Measure: Grade 3 or 4 adverse events

Time: 96 weeks

Description: Compare treatment discontinuation of study medication due to adverse effect experienced by participants through 96 weeks

Measure: Treatment discontinuation of study medication due to adverse effect

Time: 96 weeks

Description: Compare changes in fasting lipids (total cholesterol, LDL, HDL, and triglycerides) at entry, 48 weeks, and 96 weeks

Measure: Change in fasting lipids

Time: Entry, 48 weeks, and 96 weeks

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 M184V

Any antiretroviral history (even before routine virologic monitoring became standard of care) that would suggest the presence of the M184V mutation should be considered exclusionary 7. ALT ≥5 X ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin) 8. Severe hepatic impairment (Child Pugh Class C) 9. Anticipated need for antiviral therapy for HCV 10. --- M184V ---



HPO Nodes


HPO:
Osteopenia
Genes 208
PIGY MKRN3 SOX3 ADCY10 SNORD115-1 TMEM67 ERCC2 B4GALT7 EED ERCC3 IRX5 ATP7A PSAP GPAA1 ZMPSTE24 GCM2 AVP PDGFRB ESR1 CYP19A1 RNF113A TRPS1 NAGA GATA1 PSMB8 GBA IPW PWRN1 TCIRG1 DNAJC21 CDH23 SRP54 ANO5 CCND1 NDN GFI1 PTH1R MRPS22 PLEKHM1 DDOST PHGDH SNORD116-1 HESX1 STAT1 SLC39A8 SLC39A13 B3GAT3 FGF17 STN1 STAT3 RNU4ATAC MEN1 XYLT2 SEC24D IFITM5 ANOS1 MGAT2 SLC9A3R1 FBN1 FBN2 KISS1R ANTXR2 RNF125 MBTPS2 BRAF PROKR2 COG1 KCNJ1 P3H1 HECW2 GLI2 HPGD HS6ST1 RECQL4 GORAB NPAP1 HRAS PSMC3IP GTF2H5 PYCR1 ALDH18A1 CRIPT FGF8 MAFB TRPV6 TAC3 FGFR1 TACR3 FGFR2 FLRT3 MMP1 CDC73 TAF1 MMP2 GNAS PWAR1 HERC2 COX4I2 UROS HSD17B4 KISS1 PLOD2 EIF2AK3 GNRH1 GNRHR PLS3 SEC23A NOTCH2 FKBP14 GNPAT CRTAP PDE11A CHST3 COL1A1 PMM2 PROK2 KRAS FKBP10 TCF4 COL7A1 EFL1 PSAT1 FAT4 NPR2 MAGEL2 PLOD3 NRAS LHX4 TAPT1 NUP107 ADAMTS2 CLIP2 CTC1 GPR35 FOS POLE SMARCAL1 GNPTAB DUSP6 AGPAT2 GLIS3 BAZ1B FARSB B3GALT6 POU1F1 CHD7 AIP CAV1 PPARG RFC2 SLC7A7 GTF2IRD1 SKI SERPINH1 TMEM38B CREB3L1 RSPRY1 POLR3A MKRN3-AS1 MST1 SLC17A5 LIFR MLXIPL LIMK1 GTF2E2 SH3PXD2B IARS2 PIGT IGF1 OTX2 GTF2I MTAP NSMF GZF1 SLC12A1 LMNA WDR11 SLC34A1 P4HB SBDS IER3IP1 SCARB2 SPRY4 FSHR PRKACA DCHS1 GEMIN4 MPLKIP PRKAR1A ELANE LRP5 SMARCD2 CAVIN1 BSCL2 NR5A1 ELN SPIDR FUT8 IL17RD SNRPN TBL2 PRLR UNC80 ADAMTSL2 RPL11 ATP6V0A2 BMP15 PROP1