Clinical trial NCT01295034: Vitamin D Supplements for HIV-positive Patients on cART
Official title: Vitamin D Supplements for HIV-positive Patients on cART
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-associated Co-morbidities
Keywords: HIV
combination antiretroviral therapy
vitamin D
low bone density
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2011-02-14
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ability of vitamin D to modulate the immune system and strengthen bones may mitigate the adverse medication consequences of HIV/AIDS, but little is known about either the health benefits of vitamin D supplements, or about the optimal dosing regimen for patients on highly active antiretroviral therapy (HAART). This trial is a comparison of two regimens for administering vitamin D and calcium to HIV-positive individuals taking antiviral medications. This study will help physicians make evidence-based decisions about the most effective way to use vitamin D in their patients and enable the design of large multi-center trials in the future.

Detailed description: In the post-HAART era, patients continue to suffer from the adverse medical consequences of HIV/AIDS. The adverse effects include incomplete immune reconstitution, chronic inflammation, depression, increased risk of cardiovascular and metabolic disease, and low bone density. Clinical trials suggest that vitamin D supplements can increase bone density, reduce inflammation, alleviate depression, and increase longevity if given in adequate doses. To achieve maximum benefits, most vitamin D experts in the HIV field agree that vitamin D treatments should raise the concentration of 25-hydroxyvitamin D \[25(OH)D\] above 30 ng/ml. A growing number of HIV care providers desire an evidence-based protocol for achieving these 25(OH)D target levels. This project addresses the need for a validated protocol for treating vitamin D deficiency in HIV-positive individuals on HAART. The goal of Aim I is to conduct a 12-mo randomized, double-blinded trial comparing two dosing regimens of oral vitamin D plus 0.5 g/d of calcium in patients on stable HAART who have 25(OH)D levels ≤ 25 ng/ml and undetectable HIV viral load at baseline (100 per arm). Medication event monitoring system (MEMS) caps will be used to record supplement use and to promote adherence. Subjects in Protocol A will receive 50,000 IU/wk of vitamin D2 for 8 wk followed by 1000 IU/d of vitamin D3 for 48 wk. Subjects in Protocol B will receive 2000-4000 IU/d of vitamin D3, depending on the basal 25(OH)D level, with dose titration, as necessary, based on the slope of the initial response. The primary outcome measure is the difference in the percentage of subjects with 25(OH)D levels in the range of 30-60 ng/ml at 12 mo. The secondary outcome is the slope of the 25(OH)D response curve during various time intervals. The goal of Aim II is to compare the impact of the two protocols on markers of disease. The primary outcome measure is the change in the CD4+T cell count. Secondary outcomes include changes in CD4+ T cell subsets, markers of inflammation, markers of bone and calcium metabolism, self-reported psychological status, viral load, side effects, safety, and adherence. To our knowledge, this trial is the first head-to-head comparison of a regimen that uses a loading dose of vitamin D2 with a regimen that uses a tiered starting dose of vitamin D3. The project will yield a validated protocol for treating vitamin D deficiency in HIV-infected patients on HAART and will provide initial data about the risks and health benefits of vitamin D and calcium supplements. This information is essential for designing definitive multicenter trials in the future.

Eligibility criteria: Inclusion Criteria:

* age, 18-70 yr
* HIV-infected
* on a stable HAART regimen for at least 12 mo with an undetectable HIV viral load for 6-mo
* willing to participate
* not receiving vitamin D supplementation in a form other than vitamin D2 or vitamin D3
* not receiving treatment for bone disease
* not receiving medications known to alter bone mineralization
* not suffering from conditions known to affect vitamin D, calcium, and/or phosphate levels (including clinically significant hypocalcemia, primary hyperparathyroidism)
* not experiencing kidney disease based on GFR \> 60 min/ml/1.73 m2, 10) 25(OH)D level \< 25 ng/ml
* not meeting criteria of the National Osteoporosis Foundation for established bone disease (osteoporosis, osteomalacia) requiring immediate treatment
* not consuming more than 2.0 gm of calcium/day in food and supplements combined outside the trial
* not consuming more than 800IU/day of vitamin D outside the trial
* not suffering from an unstable medical condition likely to preclude participation in a 12 month trial
* able to ingest and absorb food and nutrients
* not pregnant or planning to become pregnant.

Exclusion Criteria:

* No history or evidence of HIV infection
* HIV viral load positive
* outside the age range

Primary outcomes:
measure: 25(OH)D Levels
timeFrame: baseline and 12 months
Secondary outcomes:
measure: CD4+T Cell Count
timeFrame: baseline and 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine Mount Sinai
name: Andrea D Branch, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McComsey GA, Tebas P, Shane E, Yin MT, Overton ET, Huang JS, Aldrovandi GM, Cardoso SW, Santana JL, Brown TT. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010 Oct 15;51(8):937-46. doi: 10.1086/656412.