Vitamin D Reabsorption in Adolescents and Young Adults With HIV Infection

Study Description

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Brief Summary:

The purpose of this study is to test the effects of Vitamin D on renal phosphate and bone loss, which are common in HIV infected adolescents and young adults being treated with tenofovir.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Dietary Supplement: Vitamin D supplement; Other: Placebo	Not Applicable

Detailed Description:

ATN 063 tests the hypothesis that in a population of adolescents and young adults with HIV infection who are being treated with tenofovir as part of an antiretroviral (ARV) combination regimen, vitamin D supplementation will decrease renal phosphate loss, increase plasma phosphate, decrease plasma PTH, and improve markers of bone turnover, including a decrease in plasma N-telopeptide and BAP.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	207 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Randomized, Placebo-controlled Trial of the Safety and Effectiveness of Vitamin D Supplement to Improve Tubular Reabsorption of Phosphate and Decrease Bone Turnover in Adolescents and Young Adults With HIV Infection Being Treated With Antiretroviral Therapy Containing Tenofovir Compared to Those Being Treated With Antiretroviral Therapy Not Containing Tenofovir
Study Start Date :	December 2007
Actual Primary Completion Date :	January 2010
Actual Study Completion Date :	January 2010

Arms and Interventions

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Arm	Intervention/treatment
Experimental: A: tenofovir/vitamin D; Vitamin D3 (cholecalciferol), 50,000 IU as a single capsule, will be administered orally to subjects in Group A (who are already taking Tenofovir) once every four weeks during study visits.	Dietary Supplement: Vitamin D supplement; Vitamin D3 (cholecalciferol), 50,000 IU as a single capsule, will be administered orally to subjects in Groups A and C once every four weeks during study visits.
Placebo Comparator: B: tenofovir/placebo; A placebo will be administered orally to subjects in Group B (who are already taking Tenofovir).	Other: Placebo; A placebo will be administered orally to subjects in Groups B and D once every four weeks during study visits.
Experimental: C: no tenofovir/vitamin D; Vitamin D3 (cholecalciferol), 50,000 IU as a single capsule, will be administered orally to subjects in Group C (who are not taking Tenofovir) once every four weeks during study visits.	Dietary Supplement: Vitamin D supplement; Vitamin D3 (cholecalciferol), 50,000 IU as a single capsule, will be administered orally to subjects in Groups A and C once every four weeks during study visits.
Placebo Comparator: D: no tenofovir/placebo; A placebo will be administered orally to subjects in Group D (who are not taking Tenofovir).	Other: Placebo; A placebo will be administered orally to subjects in Groups B and D once every four weeks during study visits.

Outcome Measures

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Primary Outcome Measures :

1. To compare the change in renal tubular reabsorption of phosphate and markers of bone turnover. [ Time Frame: Baseline, Week 4, Week 12 ]
2. To measure the safety of 50,000 IU dose of vitamin D3 [ Time Frame: Baseline, Week 4, and Week 8 ]

Secondary Outcome Measures :

1. To measure the relationship of vitamin D plasma concentrations to renal tubular reabsorption of phosphate and markers of bone turnover [ Time Frame: Baseline, Week 4, and Week 12 ]
2. To measure the relationship of tenofovir exposure to renal tubular reabsorption of phosphate and markers of bone turnover [ Time Frame: Baseline, Week 4, and Week 12 ]
3. To measure the change in tenofovir exposure and creatinine clearance [ Time Frame: Baseline, Week 4, and Week 12 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 24 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Age 18 years and 0 days through 24 years and 364 days
• HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to study entry
• Currently being treated with a stable FDA-approved ARV combination therapy, containing > 3 antiretrovirals, for > 28 days, according to HRSA guidelines. Treatment regimen will not be started or changed for the purposes of participation in this study. Subjects will be receiving therapy at the direction of their treating physician
• Willingness to remain on the same ARV combination therapy for the 12-week duration of the study
• Ability and willingness to participate in the study by providing written informed consent
• Willingness to be randomized to receive either vitamin D or placebo

Exclusion Criteria:

• Prior hypersensitivity to vitamin D
• History of arteriosclerosis, renal stones, glomerulonephritis, nephrotic syndrome, or hypercalcemia
• Lactation or current pregnancy
• Active therapy for malignancy
• Known presence of gastrointestinal disease that would interfere with drug administration or absorption
• Serological evidence of Hepatitis B surface antigen (HBsAg)
• Confirmed creatinine clearance < 90 ml/min (calculated GFR from serum creatinine using the MDRD formula)
• Grade 3 or higher clinical toxicity

Contacts and Locations

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Locations

United States, California
Children's Hopsital of Los Angeles
Los Angeles, California, United States, 90027
University of California at San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Children's Diagnostic and Treatment Center
Fort Lauderdale, Florida, United States, 33316
University of Miami
Miami, Florida, United States, 33101
University of South Florida
Tampa, Florida, United States, 33606
United States, Illinois
Stroger Hospital of Cook County
Chicago, Illinois, United States, 60612
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland Medical School
Baltimore, Maryland, United States, 21204
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Mount Sinai Hospital
New York, New York, United States, 10128
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Childrens Research Hospital
Memphis, Tennessee, United States, 38105
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936

Sponsors and Collaborators

University of North Carolina, Chapel Hill

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

Investigators

Study Chair:	Peter L Havens, M.S., M.D.	Medical College of Wisconsin

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Website for the Adolescent Trials Network for HIV/AIDS Interventions 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Havens PL, Hazra R, Stephensen CB, Kiser JJ, Flynn PM, Wilson CM, Rutledge B, Bethel J, Pan CG, Woodhouse LR, Van Loan MD, Liu N, Lujan-Zilbermann J, Baker A, Kapogiannis BG, Gordon CM, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 063 study team. Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youths treated with tenofovir disoproxil fumarate. Antivir Ther. 2014;19(6):613-8. doi: 10.3851/IMP2755. Epub 2014 Feb 17.

Havens PL, Kiser JJ, Stephensen CB, Hazra R, Flynn PM, Wilson CM, Rutledge B, Bethel J, Pan CG, Woodhouse LR, Van Loan MD, Liu N, Lujan-Zilbermann J, Baker A, Kapogiannis BG, Gordon CM, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 063 Study Team. Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin D deficiency? Antimicrob Agents Chemother. 2013 Nov;57(11):5619-28. doi: 10.1128/AAC.01096-13. Epub 2013 Sep 3.

Havens PL, Stephensen CB, Hazra R, Flynn PM, Wilson CM, Rutledge B, Bethel J, Pan CG, Woodhouse LR, Van Loan MD, Liu N, Lujan-Zilbermann J, Baker A, Kapogiannis BG, Mulligan K; Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions 063 study team. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial. Clin Infect Dis. 2012 Apr;54(7):1013-25. doi: 10.1093/cid/cir968. Epub 2012 Jan 19.

Responsible Party:	University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT00490412 History of Changes
Other Study ID Numbers:	ATN 063
First Posted:	June 22, 2007
Last Update Posted:	February 28, 2017
Last Verified:	February 2016

Keywords provided by University of North Carolina, Chapel Hill:

Vitamin D; Treatment Experienced

Additional relevant MeSH terms:

Infection; Communicable Diseases; 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