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Report for Clinical Trial NCT00647946

Developed by Shray Alag, 2020.
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: Lipod 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 Lipod Lipodystrophy This is a phase II, open-label, multicentre, randomised, two-arm study of 48 weeks duration. --- K65R ---



HPO Nodes


HPO:
Lipodystrophy
Genes 138
LDB3 PSEN1 ATP6V0A2 BSCL2 IGF1R CIDEC PSMB9 AGPAT2 LMNA TNNT2 LMNB2 ATP6V0A2 ACTN2 CAV1 FOS ATP6V1A FKTN FHL2 NEXN ZMPSTE24 LMNA SGCD DSG2 TREX1 LIPE DMD FGFR1 PRDM16 BSCL2 CIDEC PLIN1 BAG3 KCNJ6 DOLK CAV1 B4GALT7 EMD LMNA LMNA KCNJ6 POLR3A DES PDGFRB FBN1 TPM1 PPARG SYNE1 KRAS AKT2 POLD1 DDOST SPRTN FLNA TNNC1 ANKRD1 BSCL2 TNNI3 LMNA PMM2 INSR RBM28 GATAD1 ATP6V1E1 MYPN BANF1 TMPO RNASEH2B ACTC1 USP8 SLC25A24 MYH6 ALB PSMB8 PIK3R1 PSMB4 LIPE CRYAB TMEM43 CLMP NEBL RBM20 CAV1 LMNA TXNRD2 CSRP3 FUCA1 LMNA OTULIN TAF1A FHL1 MYH7 ABCC9 TCAP ADAR FBN1 CAVIN1 LAMA4 SCN5A RNASEH2C LMNA POLR3A PIK3R1 CDH23 DOLK IFIH1 RNASEH2A ZMPSTE24 SDHA PIK3CA ZMPSTE24 FBN1 PSMB8 AGPAT2 ATP6V0A2 CAP2 ALB WRN PSEN2 LMNA LMNA PPARG RAF1 TTN VCL SYNE2 LMNA SLC29A3 MYBPC3 PLN LMNA PLIN1 PPARG CAVIN1 PPCS ACTB TAZ SAMHD1 COL3A1