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Vitamin D Absorption in HIV Infected Young Adults Being Treated With Tenofovir Containing cART

This study has been completed.
Sponsor:
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
  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

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:
HIV Infections
Acquired Immunodeficiency Syndrome
Infection
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