Vitamin D Reabsorption in Adolescents and Young Adults With HIV Infection

Study Overview
=================
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.

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

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin D supplement
* Other: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 24 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: tenofovir/vitamin D<br>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<br>* 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.<br>|
| Placebo Comparator: B: tenofovir/placebo<br>A placebo will be administered orally to subjects in Group B (who are already taking Tenofovir). | Other: Placebo<br>* A placebo will be administered orally to subjects in Groups B and D once every four weeks during study visits.<br>|
| Experimental: C: no tenofovir/vitamin D<br>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<br>* 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.<br>|
| Placebo Comparator: D: no tenofovir/placebo<br>A placebo will be administered orally to subjects in Group D (who are not taking Tenofovir). | Other: Placebo<br>* A placebo will be administered orally to subjects in Groups B and D once every four weeks during study visits.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the change in renal tubular reabsorption of phosphate and markers of bone turnover. |  | Baseline, Week 4, Week 12 | 
| To measure the safety of 50,000 IU dose of vitamin D3 |  | Baseline, Week 4, and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the relationship of vitamin D plasma concentrations to renal tubular reabsorption of phosphate and markers of bone turnover |  | Baseline, Week 4, and Week 12 | 
| To measure the relationship of tenofovir exposure to renal tubular reabsorption of phosphate and markers of bone turnover |  | Baseline, Week 4, and Week 12 | 
| To measure the change in tenofovir exposure and creatinine clearance |  | Baseline, Week 4, and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D, Treatment Experienced