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Report for Clinical Trial NCT03549689

Developed by Shray Alag, 2020.
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
Group Labels: 1

Switch

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

Description: Continuation of current TAF-containing ART for 96 weeks.
Type: Drug
Group Labels: 1

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:
HP:0000938: Osteopenia
Genes 262
PDE11A MKRN3-AS1 CTC1 ATP7A B3GAT3 PMM2 FBN2 SMPD1 CHD7 TCF4 SLC39A8 P4HB IER3IP1 XYLT2 SLC34A1 IARS2 PIGT SCARB2 GLI2 BSCL2 CYP19A1 SKI NPR2 PWRN1 AGPAT2 BNC1 CTCF ANTXR2 PIGY LIMK1 FSHR PRKACA FLRT3 TBL2 TRPV6 PLEKHM1 FGFR2 ZMPSTE24 ZMPSTE24 MST1 PSMB8 GORAB AIP SLC9A3R1 MRPS22 PROKR2 CDH23 SRP54 SRP54 ANTXR2 SLC12A1 TAF1 GLIS3 LMNA SMARCAL1 SLC39A13 SPIDR SLC39A13 ATP6V0A2 HERC2 ESR1 DNAJC21 TAC3 HBB MBTPS2 HS6ST1 CRTAP DPM2 DCHS1 PSAP MEN1 TRPS1 GPAA1 EIF2AK3 STN1 FGF8 UROS ELANE SEC24D LRP5 CLIP2 ALDH18A1 FGF17 AEBP1 CAVIN1 FOS PSMC3IP FGFR1 CREB3L1 SERPINH1 RSPRY1 RECQL4 GNPAT LMNA ADAMTS2 POLR3H NOTCH2 UNC80 COL7A1 FKBP10 PROP1 RSPRY1 POLE BRAF PHGDH KRAS SNORD116-1 SLC35A2 GTF2E2 STAT1 IPW HECW2 DUSP6 PLS3 FUT8 AVP SH3PXD2B NOTCH2 NRAS NR5A1 PSAT1 KISS1R PRLR TMEM67 ANO5 STAT3 PDGFRB STAT3 FBN1 FAT4 TMEM38B COG1 MTAP GFI1 EED GBA RNF125 NSMF NAGA FKBP14 TONSL MKRN3 ADAMTSL2 IGF1 GTF2H5 MGAT2 TARS1 MMP2 IL17RD GCM2 USP9X FGFR1 PROP1 COL1A1 TACR3 NDN B4GALT7 CDC73 ANOS1 HSD17B4 MAFB SNORD115-1 GNPTAB MPLKIP COG1 IRX5 ESR1 CHST3 SKI GEMIN4 PRKAR1A KCNJ1 SGMS2 STAT1 SBDS ADAMTS2 GTF2I SMARCD2 ATP6V0A2 SOX3 KISS1 PLOD3 RPL11 POLR3A RNF113A LIFR MMP2 PLOD2 GATA1 DDOST DUSP6 HRAS SEC23A SLC7A7 ELN B4GALT7 GPAA1 ANO5 IFITM5 RNU4ATAC GPR35 NUP107 UROS KISS1R GZF1 MLXIPL LMNA PIGT CAV1 MAGEL2 FGF17 ELN PYCR1 SLC34A1 SNRPN ADCY10 PWAR1 MMP1 PMM2 FOXA2 CDH23 TCIRG1 CAVIN1 GCM2 HESX1 PPARG NPAP1 BAZ1B POU1F1 MEN1 ERCC2 LRP5 FKBP14 MMP14 HPGD GNAS TAPT1 BMP15 CCND1 DCHS1 EFL1 SLC17A5 COX4I2 FARSB CRIPT OTX2 PTH1R RFC2 ERCC3 TRPS1 P3H1 COL1A1 PROK2 DCAF17 FAT4 SLC39A8 GNRHR GNRH1 LHX4 WDR11 SPRY4 GTF2IRD1
Protein Mutations 2
H295R M184V
SNP 0