NCT03549689撤回2 期
Effect of Reducing Nucleotide Exposure on Bone Health (ReNew)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Philip Grant
- 试验地点
- 10
- 主要终点
- Percent change in lumbar spine Bone Mineral Density (BMD) at 96 weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infection, as documented by a positive 4th generation assay or by any licensed ELISA test kit confirmed by Western blot at any time prior to study entry.
- •Age ≥18 years
- •HIV-1 RNA BLQ (e.g., <20 copies/mL or other threshold based on the local viral load assay used) for at least 12 months prior to study entry excluding blips (i.e., a single measurement <200 copies/mL preceded and followed by measurements BLQ)
- •On a stable TAF-containing ART that also includes at least 2 other antiretrovirals, with no changes in the 12 months prior to entry (except for a switch to a co-formulated tablet from the component tablets or a switch from ritonavir to cobicistat)
- •Lumbar spine, femoral neck or total hip BMD T-score ≤-1.0 from a DXA scan within the past 48 weeks
- •If receiving testosterone or estrogen replacement therapy, on a stable dose for ≥3 months prior to enrollment without plan to change dose during the study period.
- •Acceptable blood laboratory values at screening visit:
- •CD4+ T-cell count ≥200 cells/µL
- •Phosphate ≥2mg/dL
- •25-hydroxyvitamin D level ≥10 ng/ml
- •Calculated creatinine clearance (CrCl) ≥50 mL/min as estimated by the Cockcroft-Gault equation*:
- •For men = CrCl (mL/min) = (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72)
- •For women, multiply the above result by 0.85
- •For women of reproductive potential, negative serum or urine pregnancy test prior to screening and a negative urine pregnancy test at the entry visit prior to randomization and agreeable to using a contraceptive of choice during the study period.
- •"Women of reproductive potential" are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) and have not undergone surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation; participant report sufficient)
排除标准
- •Current systemic glucocorticoid use
- •Lumbar spine, femoral neck or total hip BMD T-score <-3.0
- •Previous, current pharmacologic treatment, or plan for initiation of therapy for osteoporosis (i.e., bisphosphonates, teriparatide, denosumab, tamoxifen or raloxifene)
- •Previous fragility fracture (i.e., any fall from a standing height or less that resulted in a fracture)
- •History of genotypic resistance or phenotypic resistance to either DTG or 3TC. The interpretation of genotypic resistance is based on output from the Stanford HIV Resistance Database (available at https://hivdb.stanford.edu). Isolates with an interpretation of low-level resistance or higher are considered resistant.
- •History of virologic failure (i.e., confirmed HIV-1 RNA level ≥200 copies/mL after over 6 months of therapy) while on an integrase inhibitor (i.e., raltegravir, elvitegravir, bictegravir, or dolutegravir) or on lamivudine/emtricitabine prior to study enrollment. 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
- •ALT ≥5 X ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)
- •Severe hepatic impairment (Child Pugh Class C)
- •Anticipated need for antiviral therapy for HCV
- •Hepatitis B surface antigen positive or Hepatitis B DNA positive
- •Weight >300 pounds, precluding safe DXA testing
- •Breastfeeding, pregnancy, or plans to become pregnant during the study
- •Known allergy/sensitivity to DTG or 3TC.
- •Receipt or planned receipt of prohibited concomitant medications (See section 5.4)
- •Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment.
- •Any serious medical or psychiatric illness that, in the opinion of the site investigator, precludes safe participation or adherence to study procedures.
研究组 & 干预措施
Switch
Experimental
Dolutegravir (DTG) 50MG/ lamivuidne (3TC) 300MG FIXED_DOSE COMBINATION (FDC) DAILY at randomization for 96 weeks
干预措施: Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC) (Drug)
Continuation
Active Comparator
Continue current tenofovir alafenamide (TAF)-containing ART regimen from weeks 0 to 96.
干预措施: Current tenofovir alafenamide (TAF)-containing ART regimen (Drug)
结局指标
主要结局
Percent change in lumbar spine Bone Mineral Density (BMD) at 96 weeks
时间窗: Baseline and 96 weeks
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
次要结局
- Percentage change in total hip BMD at 48 weeks(Baseline, 48 weeks)
- Change in fractional excretion in phosphate(Baseline, 48 weeks, and 96 weeks)
- Percentage change in trunk fat(Baseline, 48 weeks, and 96 weeks)
- Change in urine β2-microglobulin (renal tubular marker)(Baseline, 48 weeks, and 96 weeks)
- Change in urine RBP (renal tubular marker)(Baseline, 48 weeks, and 96 weeks)
- Percentage change in total lean mass(Baseline, 48 weeks, and 96 weeks)
- Percentage change in limb fat(Baseline, 48 weeks, and 96 weeks)
- Maintenance of HIV RNA level(48 weeks and 96 weeks)
- Grade 3 or 4 adverse events(96 weeks)
- Treatment discontinuation of study medication due to adverse effect(96 weeks)
- Change in fasting lipids(Entry, 48 weeks, and 96 weeks)
- Percentage change in lumbar spine BMD at 48 weeks(Baseline and 48 weeks)
- Percentage change in total hip BMD at 96 weeks(Baseline, 96 weeks)
- Change in CTX (a bone resorption marker)(Baseline, 12 weeks, 48 weeks, and 96 weeks)
- Change in P1NP (a bone deposition marker)(Baseline, 12 weeks, 48 weeks, and 96 weeks)
- Change in urine protein(Baseline, 48 weeks, and 96 weeks)
- Change in urine albumin(Baseline, 48 weeks, and 96 weeks)
研究者
Philip Grant
Assistant Professor
Stanford University
研究点 (10)
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