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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01751646
First received: December 14, 2012
Last updated: October 28, 2014
Last verified: October 2014
  Purpose

This is a 96 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: MVI Tablet
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 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Compare the percent change from baseline to week 96 in DXA-measured BMD [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    To compare the percent change from baseline to week 96 in DXA-measured BMD at the spine for the randomized study groups.


Secondary Outcome Measures:
  • BMC of whole body and BMD of spine, total hip, and femoral neck - compare at different timepoints [ Time Frame: 96 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 24, change from baseline to week 48, and change from baseline to week 96 by randomized study group, with analyses using measured BMC/BMD and Z-scores;

  • Compare the time course of change in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX at various timepoints [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To compare the time course of change from baseline to weeks 12, 24 48, and 96, and the overall change from baseline to week 48 and baseline to week 96, in SCa, UCa / UCr, SPO4, TRP, 25-OHD, 1,25-OHD, free 1,25-OHD index, PTH, FGF23, BAP, OC, and CTX;

  • Assess renal glomerular safety by measuring change in SCr and estimated GFR at various timepoints [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To assess renal glomerular safety by measuring change in SCr and estimated GFR from baseline to weeks 12, 24 48, and 96 by randomized study group;

  • Assess renal tubular function by measuring change in TRP, UGluc, URBP/UCr ratio, UB2MG, UProt/ UCr ratio [ Time Frame: 96 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;

  • Measure change from baseline to week 48 and change from baseline to week 96 in Gluc homeostasis [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To measure change from baseline to week 48 and change from baseline to week 96 in Gluc homeostasis (fasting insulin and Gluc and calculated HOMA-IR and their relationship to changes in 25-OHD, 1,25-OHD, and free 1,25-OHD index for the randomized study groups and for different attained vitamin D serum concentrations;

  • Compare 25-OHD serum concentrations by randomized study group at various timepoints [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To compare 25-OHD serum concentrations by randomized study group at all-time points and change from baseline to week 48 and 96;

  • Compare the mean 25-OHD serum concentration and to measure the effect of concurrent treatment with EFV or ritonavir on serum 25-OHD concentrations and changes during the study [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To compare the mean 25-OHD serum concentration by randomized study group and to measure the effect of concurrent treatment with EFV or ritonavir on serum 25-OHD concentrations and changes during the study;

  • Measure the relationship of 25-OHD, 1,25-OHD, and free 1, 25-OHD serum concentrations BMD/BMC, markers of Ca-PO4-FGF23 activity, markers of bone turnover, renal glomerular and tubular toxicity, and Gluc homeostasis at various timepoints [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    To measure the relationship of 25-OHD, 1,25-OHD, and free 1, 25-OHD serum concentrations to baseline and change from baseline to week 24, baseline to week 48, and baseline to 96 in BMD/BMC, markers of Ca-PO4-FGF23 activity, markers of bone turnover, renal glomerular and tubular toxicity, and Gluc homeostasis


Estimated Enrollment: 200
Study Start Date: October 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: Vitamin D3 50,000 IU Dietary Supplement: Vitamin D3 50,000 IU
Group A: Vitamin D3 50,000 IU orally every four weeks by DOT
Dietary Supplement: MVI Tablet
A standard MVI will be supplied to all study subjects and will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca. Subjects will take one MVI tablet orally once daily.
Placebo Comparator: Group B: Vitamin D3 placebo Dietary Supplement: MVI Tablet
A standard MVI will be supplied to all study subjects and will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca. Subjects will take one MVI tablet orally once daily.
Dietary Supplement: Vitamin D3 placebo
Group B: Vitamin D3 placebo orally every four weeks by DOT

Detailed Description:

This is a 96 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 screening; no viral load above 200 copies/mL if measured within the 90 days prior to screening; and a 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, 48, and 96. 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, 48, and 96. Blood samples to measure Gluc homeostasis will be drawn at baseline and weeks 48 and 96, 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 96 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 (see section 7.0 for additional details).

  Eligibility

Ages Eligible for Study:   16 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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); 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 viral load that is below 200 copies/mL collected following initiation of TDF containing cART and greater than 90 days prior to screening; no viral load above 200 copies/mL if measured within the 90 days prior to screening; and a viral load obtained at screening that is below 200 copies/mL.
  • Currently being treated for at least 180 days 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 96-week duration of the study;
  • Willingness and ability to participate in the study, follow all study procedures for the 96-week duration, 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

Exclusion Criteria:

  • 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

Contacts
Contact: Georgine Price, MPH 301-610-4990 georgineprice@westat.com

Locations
United States, California
Children's Hopsital of Los Angeles Active, not recruiting
Los Angeles, California, United States, 90027
University of Southern California - NICHD Westat Site Recruiting
Los Angeles, California, United States, 90033
Contact: Eva Operskalski    323-226-5068    eva@usc.edu   
Principal Investigator: Andrea Kovacs, MD         
United States, District of Columbia
Childrens National Medical Center Active, not recruiting
Washington, District of Columbia, United States, 20010
United States, Florida
Children's Diagnostic and Treatment Center - NICHD Westat Site Recruiting
Fort Lauderdale, Florida, United States, 33316
Contact: Amy Inman, BS    954-728-1050    ainman@browardhealth.org   
Principal Investigator: Ana Puga         
University of Florida Jacksonville - NICHD Westat Site Recruiting
Jacksonville, Florida, United States, 32211
Contact: Tabetha Gayton, PhD    904-244-5331    Tabetha.gayton@jax.ufl.edu   
Principal Investigator: Mobeen Rathore, MD         
University of Miami School of Medicine Active, not recruiting
Miami, Florida, United States, 33101
University of South Florida Active, not recruiting
Tampa, Florida, United States, 33606
United States, Illinois
Stroger Hospital and the CORE Center Active, not recruiting
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane Medical Center Active, not recruiting
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University Active, not recruiting
Baltimore, Maryland, United States, 21287
Johns Hopkins University - NICHD Westat Site Recruiting
Baltimore, Maryland, United States, 21287
Contact: Thuy C Anderson, BSN    443-287-8942    tander34@jhmi.edu   
Principal Investigator: Allison Agwu, M.D.         
United States, Massachusetts
Fenway Institute Active, not recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Wayne State University Active, not recruiting
Detroit, Michigan, United States, 48201
United States, New York
Montefiore Medical Center Active, not recruiting
Bronx, New York, United States, 10467
United States, Pennsylvania
Children's Hopsital of Philadelphia - NICHD Westat Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sheri McDougall, MS    215-590-0416    mcdougall@email.chop.edu   
Principal Investigator: Richard Rutstein, MD         
Children's Hospital of Philadelphia Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Childrens Research Hospital Active, not recruiting
Memphis, Tennessee, United States, 38105
United States, Texas
Baylor College of Medicine Active, not recruiting
Houston, Texas, United States, 77030
Puerto Rico
San Juan City Hospital (Puerto Rico) - NICHD Westat Site Recruiting
San Juan, Puerto Rico, 00936-5067
Contact: Lourdes Angeli Nieves, MPH    (787) 765-4186    LAngeli@SanJuanCapital.com   
Principal Investigator: Midnela Acevedo, MD         
Sponsors and Collaborators
Investigators
Study Chair: Peter Havens, MD MACC Fund Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01751646     History of Changes
Other Study ID Numbers: ATN 109
Study First Received: December 14, 2012
Last Updated: October 28, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Communicable Diseases
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Cholecalciferol
Ergocalciferols
Tenofovir
Vitamin D
Vitamins
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014