SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00647946

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase II, Open-Label, Multicentre, Randomised, Comparator Study of Substitution With Tenofovir or Abacavir in HIV-1 Infected Individuals, With a Viral Load < 50 Copies/mL, Receiving a Thymidine Analogue (Zidovudine or Stavudine) as Part of Their Highly Active Antiretroviral Therapy (HAART)

A previous study substituting zidovudine or stavudine to abacavir in patients with severe or moderate lipoatrophy has shown an increase in limb fat by DEXA. This study was conducted over a 24-week period and although improved outcomes were documented by objective measures, DEXA scans, subjective observation did not correspond. Longer-term follow up of these patients is required. This 48 week study is designed to compare the substitution of the thymidine analogues zidovudine (ZDV) or stavudine (D4T) with either tenofovir DF or abacavir, in patients treated with highly active antiretroviral therapy (HAART), and show improved outcomes on total limb fat mass, improved body shape by dual energy x-ray absorptiometry (DEXA) and computed tomography (CT) scans and improved cholesterol and triglycerides.

NCT00647946 Lipodystrophy
MeSH: Lipodystrophy
HPO: Lipodystrophy

2 Interventions

Name: tenofovir DF

Description: tenofovir DF 300mg once daily along with the other antiviral drugs

Type: Drug

A

Name: abacavir 300mg twice daily

Description: abacavir 300mg twice daily along with the other antiviral drugs

Type: Drug

B


Primary Outcomes

Measure: Change in total limb fat mass by DEXA scan

Time: 24 and 48 weeks

Secondary Outcomes

Measure: Change in VAT by single slice L4 abdominal CT scan

Time: 24 and 48 weeks

Measure: Change in viral load measurements and CD4 cell count

Time: 24 and 48 Weeks

Measure: Change in fasting cholesterol and triglycerides

Time: 24 and 48 Weeks

Measure: Change in blood insulin and fasting glucose

Time: 24 and 48 Weeks

Measure: Change in blood lactate and anion gap

Time: 24 and 48 Weeks

Measure: Change in bone mineral density by DEXA scan

Time: 24 and 48 Weeks

Measure: Incidence of adverse events

Time: Upto 48 weeks

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 K65R

Women of childbearing potential must agree to use a barrier method of contraception - Female subjects must not be pregnant or lactating - Subjects who in the opinion of the investigator have the ability to understand and provided written informed consent to participate in the trial - Subjects who in the opinion of the investigator have clinical lipoatrophy at > 1 body/facial site - Subjects currently receiving nucleoside analogue regimen including stavudine (d4T) or zidovudine (ZDV) - Subjects who are stable on current therapy for >16 weeks - Subjects with no prior exposure to tenofovir, abacavir, or adefovir - Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations - Subjects with documented viral load <50 copies/ml on 2 consecutive occasions including most recent clinic attendance Exclusion Criteria: - Subjects who in the investigator's opinion are unlikely to complete the 48 week trial period - Currently active opportunistic disease or documented wasting syndrome - Currently receiving chemotherapy for malignancy - Subjects who in the opinion of the investigator are unlikely to retain viral response after switching based on treatment or transmission history - Currently receiving an insulin sensitising agent (glitazone or metformin) - Anabolic steroids in the last 16 weeks other than testosterone at replacement doses (<250mg/2 weekly) - Growth hormone use in the last 16 weeks - Statin therapy (HMG CoA reductase inhibitor) commenced in the last 16 weeks (patients stable on statins my be included) - Current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subjects' ability to comply with the dosing schedule and protocol evaluations - Receiving concurrent medications that - in the opinion of the investigator and according to drug product labelling - will result in clinically significant interactions with tenofovir or abacavir - Pregnant or breast feeding - Previously received more than 3 months zidovudine monotherapy Inclusion Criteria: - Subjects who are male or female > 18 years of age - Subjects who are HIV-1 infected as documented by a licensed HIV-1 antibody ELISA - Female subjects of childbearing potential must have a negative serum pregnancy test (beta-HCG) within 28 days of trial day 1. --- K65R ---

Women of childbearing potential must agree to use a barrier method of contraception - Female subjects must not be pregnant or lactating - Subjects who in the opinion of the investigator have the ability to understand and provided written informed consent to participate in the trial - Subjects who in the opinion of the investigator have clinical lipoatrophy at > 1 body/facial site - Subjects currently receiving nucleoside analogue regimen including stavudine (d4T) or zidovudine (ZDV) - Subjects who are stable on current therapy for >16 weeks - Subjects with no prior exposure to tenofovir, abacavir, or adefovir - Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations - Subjects with documented viral load <50 copies/ml on 2 consecutive occasions including most recent clinic attendance Exclusion Criteria: - Subjects who in the investigator's opinion are unlikely to complete the 48 week trial period - Currently active opportunistic disease or documented wasting syndrome - Currently receiving chemotherapy for malignancy - Subjects who in the opinion of the investigator are unlikely to retain viral response after switching based on treatment or transmission history - Currently receiving an insulin sensitising agent (glitazone or metformin) - Anabolic steroids in the last 16 weeks other than testosterone at replacement doses (<250mg/2 weekly) - Growth hormone use in the last 16 weeks - Statin therapy (HMG CoA reductase inhibitor) commenced in the last 16 weeks (patients stable on statins my be included) - Current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subjects' ability to comply with the dosing schedule and protocol evaluations - Receiving concurrent medications that - in the opinion of the investigator and according to drug product labelling - will result in clinically significant interactions with tenofovir or abacavir - Pregnant or breast feeding - Previously received more than 3 months zidovudine monotherapy Lipodystrophy Lipodystrophy This is a phase II, open-label, multicentre, randomised, two-arm study of 48 weeks duration. --- K65R ---



HPO Nodes


HPO:
Lipodystrophy
Genes 104
TPM1 COL3A1 RNASEH2B KRAS SLC25A24 RAF1 ATP6V1A FLNA TREX1 MYH6 ATP6V1E1 MYH7 SLC29A3 B4GALT7 ZMPSTE24 PSEN1 PSEN2 NEBL DSG2 RNASEH2A PDGFRB SGCD POLD1 FOS SYNE1 TAF1A BAG3 AGPAT2 INSR ACTB PSMB4 DOLK WRN PSMB8 PSMB9 ACTC1 LAMA4 CDH23 B3GALT6 ABCC9 SAMHD1 TMEM43 LMNB2 ACTN2 CAV1 TXNRD2 RBM28 PPARG PPCS ADAR TTN TCAP BANF1 RBM20 CSRP3 DDOST POLR3A CRYAB IFIH1 DES USP8 LDB3 LIPE FBN1 IGF1R OTULIN LMNA FKTN PIK3CA PIK3R1 KCNJ6 CIDEC ANKRD1 RNASEH2C MYPN SYNE2 SCN5A GATAD1 TMPO AKT2 CLMP CAVIN1 BSCL2 FGFR1 ALB FUCA1 EMD DMD SPRTN TNNC1 FHL1 TNNI3 FHL2 PLIN1 TNNT2 PLN PRDM16 NEXN SDHA TAZ VCL ATP6V0A2 PMM2 MYBPC3