Clinical trial NCT00490412: Vitamin D Reabsorption in Adolescents and Young Adults With HIV Infection
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Vitamin D
Treatment Experienced
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
First posted: 2007-06-22
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Maximum age (years): 24
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: To compare the change in renal tubular reabsorption of phosphate and markers of bone turnover.
timeFrame: Baseline, Week 4, Week 12
measure: To measure the safety of 50,000 IU dose of vitamin D3
timeFrame: Baseline, Week 4, and Week 8
Secondary outcomes:
measure: To measure the relationship of vitamin D plasma concentrations to renal tubular reabsorption of phosphate and markers of bone turnover
timeFrame: Baseline, Week 4, and Week 12
measure: To measure the relationship of tenofovir exposure to renal tubular reabsorption of phosphate and markers of bone turnover
timeFrame: Baseline, Week 4, and Week 12
measure: To measure the change in tenofovir exposure and creatinine clearance
timeFrame: Baseline, Week 4, and Week 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hopsital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic and Treatment Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Stroger Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical School
state: Maryland
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Childrens Research Hospital
state: Tennessee
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Medical College of Wisconsin
name: Peter L Havens, M.S., M.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.