A Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Effectiveness of Vitamin D3 50,000 IU Every 4 Weeks to Increase Bone Mineral Density and Decrease Tenofovir-Induced Hyperparathyroidism in Youth With HIV Infection Being Treated With Tenofovir-Containing Combination Antiretroviral Therapy (cART)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 214
- 试验地点
- 34
- 主要终点
- Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups
研究概览
简要总结
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) who are currently being treated with cART that includes tenofovir disoproxil fumarate (TDF) as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved antiretroviral (ARV) drugs for at least 180 days.
详细描述
This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days. Subjects must have at least one documented viral load that is below 200 copies/mL that is collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
Treatment assignments will be balanced by subject sex at birth, age (<20 years vs. >=20 years), and race (African American vs. other). Enrolled subjects will be randomized to receive vitamin D3 50000 IU or matching placebo, given orally every four weeks by DOT. In addition to the randomized study agent, all subjects will receive a MVI to be taken orally once daily. This "standard" MVI will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca.
Dual energy x-ray absorptiometry (DXA) measurement of bone mineral content (BMC)/bone mineral density (BMD) of whole body, spine, and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-phosphorous (PO4) axis, parathyroid hormone (PTH)-FGF23-vitamin D signaling, bone turnover, and renal glomerular and tubular function will occur at baseline and study weeks 12, 24, and 48. Blood samples to measure Gluc homeostasis will be drawn at baseline and week 48, and will be run by batch analysis.
Safety, measured by serum calcium (SCa) and serum creatinine (SCr), will be monitored by subject's record review at study sites since these labs will generally be measured as a part of routine clinical care. The Adolescent Medicine Trials Network for HIV/AIDS Interventions 109 (ATN 109) study will use the SCa and SCr values obtained within 10 weeks at the time of the visit beginning at the baseline visit. If these evaluations were not performed within the prior 10 weeks they will be drawn at the time of each visit. Viral load and cluster of differentiation 4 (CD4) cell count results will be recorded for this study, ATN 109, at screening, baseline and study weeks 12, 24, 48, and Post-Week 48 provided the evaluations were done within the protocol specified timeframe. If the evaluations were not performed within the protocol specified timeframes they will be drawn at the time of the visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 24 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be considered eligible for enrollment, an individual must meet the criteria listed below at the time of randomization:
- •NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- •Age 16 years and 0 days to 24 years and 364 days;
- •Behaviorally infected with HIV (e.g., sexual contact, injection drug use; not infected by perinatal transmission, blood transfusion, or at age younger than 9 years);
- •HIV-1 infection as documented in subject's medical record by at least one of the following criteria:
- •reactive HIV screening test result with an antibody based FDA-licensed assay followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1 Indirect Immunofluorescence, Antibody Differentiation Assay (Multispot)); or
- •positive HIV-1 DNA polymerase chain reaction (PCR) assay; or
- •plasma HIV-1 quantitative RNA assay >1,000 copies/mL; or
- •positive plasma HIV-1 RNA qualitative assay
- •Subjects must have at least one documented HIV viral load that is below 200 copies/mL collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no HIV viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
- •Currently being treated for at least 180 days by the time of randomization with a TDF containing cART with at least 2 other FDA approved ARVs (NOTE: This may include a TDF-containing fixed drug combination medication);
- •Negative serum hepatitis B surface antigen (HBsAg) at screening or by history within 4 weeks prior to screening (see section 7.1.3);
- •Willingness and ability to remain on the same cART regimen for the duration of study participation;
- •Willingness and ability to participate in the study, follow all study procedures for the duration of study participation, and provide written informed consent or assent with parental permission, if applicable; and
- •For females of child-bearing potential, agreement to use a minimum of one proven-effective method of birth control and willingness to postpone pregnancy for the duration of study participation (see section 5.3.2 for permitted hormonal contraceptives)
排除标准
- •To be considered eligible for enrollment, an individual must not meet any of the criteria listed below at the time of randomization:
- •NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- •Prior hypersensitivity to vitamin D;
- •History of sarcoidosis, arteriosclerosis, renal stones, glomerulonephritis, interstitial kidney disease, nephrotic syndrome, hypercalcemia, osteoporosis and/or other bone diseases, clinical diagnosis of hypoparathyroidism or hyperparathyroidism;
- •Lactation or pregnancy currently or within the past 24 weeks;
- •Chemotherapy or radiation therapy for malignancy within the past 12 months;
- •Known presence of GI disease that, in the opinion of the clinician, would interfere with study agent administration or absorption (e.g. Crohn's, Colitis);
- •For subjects ≥ 18 years, confirmed creatinine clearance < 70 ml/min (estimated glomerular filtration rate (GFR) from SCr using Cockcroft and Gault (CG) equation) and for subjects <18 years, confirmed creatinine clearance < 70ml/min/1.73m2 (estimated GFR from SCr using Schwartz formula (see section 3.5). (Estimated GFR may be calculated using the formulae programmed on the ATN website);
- •SCa > Upper Limit Normal (ULN) for local laboratory values (see section 7.1.3);
- •Active Grade 3 or higher clinical or laboratory toxicity except atazanavir (ATV) associated indirect hyperbilirubinemia (see section 9.5.2.2);
- •Weight is > 350 pounds (lbs) or 159 kilograms (kgs);
- •Positive hepatitis C antibody by history or at screening (see section 7.1.3); and
- •Use of any medications as specified in sections 5.3.1, 5.3.3 and 5.
- •Females Only: Use of certain hormonal contraceptives as specified in the protocol.
研究组 & 干预措施
Group A: Vitamin D3 50,000 IU
Subjects randomized to Group A will receive Vitamin D3 50,000 IU orally every four weeks by directly observed therapy (DOT). In addition all subjects receive a multivitamin (MVI) that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Calcium (Ca). Subjects will self-administer one MVI tablet orally once daily.
干预措施: Vitamin D3 50,000 IU (Dietary Supplement)
Group B: Vitamin D3 placebo
Subjects randomized to Group B will receive Vitamin D3 placebo orally every four weeks by DOT. In addition all subjects receive a MVI that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Ca. Subjects will self-administer one MVI tablet orally once daily.
干预措施: Vitamin D3 placebo (Dietary Supplement)
结局指标
主要结局
Percent Change From Baseline to Week 48 in Dual Energy X-ray Absorptiometry (DXA)-Measured BMD at the Spine for the Randomized Study Groups
时间窗: Baseline and wk 48
Percent change from baseline to week (wk) 48 in DXA-measured BMD at the spine for the randomized study groups. Lumbar spine BMD (L1 - L4) (g/cm2) change from Baseline to wk 48 visit.
次要结局
- Change From Baseline to Week 24 in OC(Baseline and week 24)
- Change From Baseline to Week 12 in BAP(Baseline and wk 12)
- Change From Baseline to Week 12 in PTH(Baseline and wk 12)
- Change From Baseline to Week 24 in 25-OHD(Baseline and wk 24)
- Change From Baseline to Week 48 in BAP(Baseline and wk 48)
- Change From Baseline to Week 12 in FGF23(Baseline and wk 12)
- 25-OHD Serum Concentration by Randomized Study Group at Week 12(Week 12)
- Percent Change From Baseline to Week 24 of Total Hip BMD for the Randomized Study Groups(Baseline and week 24)
- Percent Change From Baseline to Week 48 of Total Hip BMD for the Randomized Study Groups(Baseline and week 48)
- Change in SCr From Baseline to Week 24.(Baseline and week 24)
- Percent Change From Baseline to Week 48 of BMC of Whole Body for the Randomized Study Groups(Baseline and week 48)
- Change From Baseline to Week 48 of Total Hip BMD Z-score for the Randomized Study Groups(Baseline and week 48)
- Change From Baseline to Week 24 in Serum Calcium (SCa)(24 weeks)
- Change From Baseline to Week 12 in OC(Baseline and week 12)
- Percent Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD for the Randomized Study Groups(Baseline and week 24)
- Percent Change From Baseline to Week 24 of Femoral Neck BMD for the Randomized Study Groups(Baseline and week 24)
- Change From Baseline to Week 48 of Femoral Neck BMD Z-score for the Randomized Study Groups(Baseline and week 48)
- Change From Baseline to Week 24 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups(Baseline and week 24)
- Change From Baseline to Week 48 of Lumbar Spine (L1-L4) BMD Z-score for the Randomized Study Groups(Baseline and week 48)
- Percent Change From Baseline to Week 48 of Femoral Neck BMD for the Randomized Study Groups(Baseline and week 48)
- Change From Baseline to Week 24 of Femoral Neck BMD Z-score for the Randomized Study Groups(Baseline and week 24)
- Change From Baseline to Week 24 of Total Hip BMD Z-score for the Randomized Study Groups(Baseline and week 24)
- Percent Change From Baseline to Week 24 of BMC of Whole Body for the Randomized Study Groups(Baseline and week 24)
- Change From Baseline to Week 24 in CTX(Baseline and week 24)
- Change From Baseline to Week 48 in FGF23(Baseline and wk 48)
- Change From Baseline to Week 12 in Actual Free 1,25-OHD(Baseline and wk 12)
- Change From Baseline to Week 48 in 1,25-OHD(Baseline and wk 48)
- Change From Baseline to Week 12 in TRP %(Baseline and wk 12)
- Change From Baseline to Week 48 in TRP %(Baseline and wk 48)
- Change in Estimated GFR From Baseline to Week 48.(Baseline and wk 48)
- Change in UGluc From Baseline to Week 48(Baseline and wk 48)
- Change in URBP/UCr Ratio From Baseline to Week 48(Baseline and wk 48)
- Change in UB2MG From Baseline to Week 48(Baseline and wk 48)
- Change From Baseline to Week 48 in CTX(Baseline and week 48)
- Change in SCr From Baseline to Week 48.(Baseline and week 48)
- Change From Baseline to Week 48 in Glucose Homeostasis (Fasting Glucose)(Baseline and week 48)
- Change From Baseline to Week 48 in Glucose Homeostasis (Homeostasis Model Assessment of Insulin Resistance (HOMA-IR))(Baseline and week 48)
- Change From Baseline to Week 12 in Serum Calcium (SCa)(Baseline and wk 12)
- Change From Baseline to Week 24 in Actual Free 1,25-OHD(Baseline and wk 24)
- Change From Baseline to Week 48 in Actual Free 1,25-OHD(Baseline and wk 48)
- Change From Baseline to Week 12 in SPO4(Baseline and wk 12)
- Change From Baseline to Week 48 in UCa/Ucr(Baseline and wk 48)
- Change in Estimated GFR From Baseline to Week 12.(Baseline and wk 12)
- Effect of Concurrent Treatment With Efavirenz on 25-OHD Serum Concentration: Concentration at Week 48 by Efavirenz Use(Week 48)
- Effect of Concurrent Treatment With Ritonavir on 25-OHD Serum Concentration: Concentration at Baseline by Ritonavir Use(Baseline)
- Change in SCr From Baseline to Week 12.(Baseline and week 12)
- Change From Baseline to Week 48 in OC(Baseline and wk 48)
- Change From Baseline to Week 24 in 1,25-OHD(Baseline and wk 24)
- Change From Baseline to Week 48 in 25-OHD(Baseline and wk 48)
- Change From Baseline to Week 24 in TRP %(Baseline and wk 24)
- Change From Baseline to Week 48 in SPO4(Baseline and wk 48)
- Change in UProt/ UCr Ratio From Baseline to Week 48(Baseline and wk 48)
- 25-OHD Serum Concentration by Randomized Study Group at Week 48(Week 48)
- Effect of Concurrent Treatment With Efavirenz on 25-OHD Serum Concentration: Concentration at Baseline by Efavirenz Use(Baseline)
- Effect of Concurrent Treatment With Ritonavir on 25-OHD Serum Concentration: Concentration at Week 48 by Ritonavir Use(Week 48)
- Change From Baseline to Week 48 in Glucose Homeostasis (Fasting Insulin)(Baseline and 48 weeks)
- Change From Baseline to Week 48 in Serum Calcium (SCa)(Baseline and wk 48)
- Change From Baseline to Week 12 in CTX(Baseline and week 12)
- Change From Baseline to Week 24 in BAP(Baseline and wk 24)
- Change From Baseline to Week 24 in FGF23(Baseline and wk 24)
- Change From Baseline to Week 24 in PTH(Baseline and wk 24)
- Change From Baseline to Week 48 in PTH(Baseline and wk 48)
- Change From Baseline to Week 12 in 1,25-OHD(Baseline and wk 12)
- Change From Baseline to Week 12 in 25-OHD(Baseline and wk 12)
- Change From Baseline to Week 12 in UCa/Ucr(Baseline and wk 12)
- Change From Baseline to Week 24 in SPO4(Baseline and wk 24)
- Change From Baseline to Week 24 in UCa/Ucr(Baseline and wk 24)
- Change in Estimated GFR From Baseline to Week 24.(Baseline and wk 24)
- 25-OHD Serum Concentration by Randomized Study Group at Week 24(Week 24)
- Effect of Concurrent Treatment With Efavirenz on 25-OHD Serum Concentration: Change in Concentration From Baseline to Week 48 by Efavirenz Use(Baseline and wk 48)
- Effect of Concurrent Treatment With Ritonavir on 25-OHD Serum Concentration: Change in Concentration From Baseline to Week 48 by Ritonavir Use(Baseline and wk 48)