Vitamin D Supplements for HIV-positive Patients on cART

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.

Study Overview

• Status: Completed
• Conditions: HIV-associated Co-morbidities
• Intervention / Treatment: Dietary supplement: conventional vitamin D treatment; Drug: tiered/titrated vitamin D dosing

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: conventional vitamin D treatment; Subjects in Protocol A (the conventional/active placebo arm) will receive 50,000 IU/wk of vitamin D2 for 8 wk followed by 1000 IU/d of vitamin D3 for 48 wk.	Dietary supplement: conventional vitamin D treatment; Subjects in Protocol A (the conventional/active placebo arm) will receive 50,000 IU/wk of vitamin D2 for 8 wk followed by 1000 IU/d of vitamin D3 for 48 wk.
Experimental: tiered/titrated vitamin D dosing; 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, for a total duration of treatment of 12 mo.	Drug: tiered/titrated vitamin D dosing; 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, for a total duration of treatment of 12 mo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25(OH)D Levels	The difference in the percentage of subjects with 25(OH)D levels in the range of 30-60 ng/ml at 12 mo between the two arms.	baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4+T Cell Count	The change in the CD4+T cell count between the two arms.	baseline and 12 months

Collaborators and Investigators

• Sponsor: Andrea Branch
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Andrea D Branch, PhD, Icahn School of Medicine Mount Sinai

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 14, 2011

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 6, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: HIV; vitamin D; combination antiretroviral therapy; low bone density
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; HIV Seropositivity; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: GCO 10-0679; R01DA031095 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided