Vitamin D Absorption in HIV Infected Young Adults Being Treated With Tenofovir Containing cART
This study has been completed.
Sponsor:
Westat
Collaborators:
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Westat
ClinicalTrials.gov Identifier:
NCT01751646
First received: December 14, 2012
Last updated: July 1, 2016
Last verified: July 2016
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Purpose
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.
| Condition | Intervention |
|---|---|
|
HIV Infection |
Dietary Supplement: Vitamin D3 50,000 IU Dietary Supplement: Vitamin D3 placebo |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Diagnostic |
| Official Title: | 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 |
Resource links provided by NLM:
Further study details as provided by Westat:
Primary Outcome Measures:
- Compare the percent change from baseline to week 48 in DXA-measured BMD at the spine for the randomized study groups [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]To compare the percent change from baseline to week 48 in DXA-measured BMD at the spine for the randomized study groups.
Secondary Outcome Measures:
- Compare change from baseline to week 24 of BMC of whole body and BMD of spine, total hip, and femoral neck for the randomized study groups [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]For BMC of whole body and BMD of spine, total hip, and femoral neck, compare change from baseline to week 24by randomized study group, with analyses using measured BMC/BMD and Z-scores;
- Compare change from baseline to week 48 of BMC of whole body and BMD of spine, total hip, and femoral neck for the randomized study groups [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]For BMC of whole body and BMD of spine, total hip, and femoral neck, compare change from baseline to week 48, by randomized study group, with analyses using measured BMC/BMD and Z-scores;
- Compare the time course of change from baseline to week 12 in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]To compare the time course of change from baseline to weeks 12 in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX;
- Compare the time course of change from baseline to week 24 in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]To compare the time course of change from baseline to week 24 in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX
- Compare the time course of change from baseline to week 48 in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]To compare the time course of change from baseline to week 48 in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX;
- Change in in SCr and estimated GFR from baseline to week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]To assess renal glomerular safety by measuring change in SCr and estimated GFR from baseline to week 12 by randomized study group;
- Change in in SCr and estimated GFR from baseline to week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]To assess renal glomerular safety by measuring change in SCr and estimated GFR from baseline to week 24 by randomized study group;
- Change in in SCr and estimated GFR from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]To assess renal glomerular safety by measuring change in SCr and estimated GFR from baseline to week 48 by randomized study group;
- Change in TRP, UGluc, URBP/UCr ratio, UB2MG, UProt/ UCr ratio from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]To assess renal tubular function by measuring change in TRP, UGluc, URBP/UCr ratio, UB2MG, UProt/ UCr ratio by randomized study group;
- Change from baseline to week 48 in glucose homeostasis (Fasting insulin) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Change from baseline to week 48 in glucose homeostasis (Fasting glucose) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Change from baseline to week 48 in glucose homeostasis (homeostasis model of insulin resistance (HOMA-IR) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Compare change in baseline to week 12 in 25-OHD serum concentrations by randomized study group [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Compare change in baseline to week 24 in 25-OHD serum concentrations by randomized study group [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Compare change in baseline to week 48 in 25-OHD serum concentrations by randomized study group. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Compare the LS mean 25-OHD serum concentration over the 48 week time period between the randomized study groups. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Mean BMD/BMC at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- The change in mean BMD/BMC between Baseline and Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- The change in mean BMC/BMC between Baseline and Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Mean Ca-PO4-FGF23 activity marker at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- The change in mean Ca-PO4-FGF23 activity marker between Baseline and Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- The change in mean Ca-PO4-FGF23 activity marker between Baseline and Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Mean value of bone turnover marker at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- The change in mean value of bone turnover marker between Baseline and Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- The change in mean value of bone turnover marker between Baseline and Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Number of subjects with renal glomerular and tubular toxicity at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- Number of subjects with renal glomerular and tubular toxicity at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Number of subjects with renal glomerular and tubular toxicity at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Mean glucose homeostasis (fasting insulin) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- Change in mean glucose homeostasis (fasting insulin) between Baseline and Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change in mean glucose homeostasis (fasting insulin) between Baseline and Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Mean glucose homeostasis (fasting glucose) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- Change in mean glucose homeostasis (fasting glucose) between Baseline and Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change in mean glucose homeostasis (fasting glucose) between Baseline and Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Mean glucose homeostasis (HOMA-IR) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- Change in mean glucose homeostasis (HOMA-IR) between Baseline and Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Change in mean glucose homeostasis (HOMA-IR) between Baseline and Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 214 |
| Study Start Date: | October 2012 |
| Study Completion Date: | June 2016 |
| Primary Completion Date: | June 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Dietary Supplement: Vitamin D3 50,000 IU
Group A: Vitamin D3 50,000 IU orally every four weeks by DOT
Other Name: Vitamin D3
|
|
Placebo Comparator: 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.
|
Dietary Supplement: Vitamin D3 placebo
Group B: Vitamin D3 placebo orally every four weeks by DOT
Other Name: Placebo
|
Detailed Description:
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.
DXA measurement of whole-body BMC, and BMD at spine and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-PO4 axis, 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 SCa and 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 ATN109 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 the visit. Viral load and CD4 cell count results will be recorded for the ATN109 study 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 are not performed within the protocol specified timeframes they will be drawn at the time of the visit.
Eligibility| Ages Eligible for Study: | 16 Years to 24 Years (Child, Adult) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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 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)
Exclusion Criteria:
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 GFR from SCr using 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 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 5.4.
- Females Only: Use of certain hormonal contraceptives as specified in the protocol.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01751646
Please refer to this study by its ClinicalTrials.gov identifier: NCT01751646
Locations
| United States, California | |
| Children's Hopsital of Los Angeles | |
| Los Angeles, California, United States, 90027 | |
| University of Southern California - NICHD Westat Site | |
| Los Angeles, California, United States, 90033 | |
| United States, District of Columbia | |
| Childrens National Medical Center | |
| Washington, District of Columbia, United States, 20010 | |
| United States, Florida | |
| Children's Diagnostic and Treatment Center - NICHD Westat Site | |
| Fort Lauderdale, Florida, United States, 33316 | |
| University of Florida Jacksonville - NICHD Westat Site | |
| Jacksonville, Florida, United States, 32211 | |
| University of Miami School of Medicine | |
| Miami, Florida, United States, 33101 | |
| University of South Florida | |
| Tampa, Florida, United States, 33606 | |
| United States, Illinois | |
| Stroger Hospital and the CORE Center | |
| Chicago, Illinois, United States, 60612 | |
| United States, Louisiana | |
| Tulane Medical Center | |
| New Orleans, Louisiana, United States, 70112 | |
| United States, Maryland | |
| Johns Hopkins University - NICHD Westat Site | |
| Baltimore, Maryland, United States, 21287 | |
| Johns Hopkins University | |
| Baltimore, Maryland, United States, 21287 | |
| United States, Massachusetts | |
| Fenway Institute | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Michigan | |
| Wayne State University | |
| Detroit, Michigan, United States, 48201 | |
| United States, New York | |
| Montefiore Medical Center | |
| Bronx, New York, United States, 10467 | |
| United States, Pennsylvania | |
| Children's Hopsital of Philadelphia - NICHD Westat Site | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Tennessee | |
| St. Jude Childrens Research Hospital | |
| Memphis, Tennessee, United States, 38105 | |
| United States, Texas | |
| Baylor College of Medicine | |
| Houston, Texas, United States, 77030 | |
| Puerto Rico | |
| San Juan City Hospital (Puerto Rico) - NICHD Westat Site | |
| San Juan, Puerto Rico, 00936-5067 | |
Sponsors and Collaborators
Westat
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
Investigators
| Study Chair: | Peter Havens, MD | MACC Fund Research Center |
More Information
Additional Information:
| Responsible Party: | Westat |
| ClinicalTrials.gov Identifier: | NCT01751646 History of Changes |
| Other Study ID Numbers: | ATN 109 Version 2.0 |
| Study First Received: | December 14, 2012 |
| Last Updated: | July 1, 2016 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
Infection HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Vitamins Vitamin D Ergocalciferols |
Cholecalciferol Tenofovir Micronutrients Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |
ClinicalTrials.gov processed this record on September 29, 2016