Clinical trial NCT01798680: Trial of Vitamin D in HIV Progression
Official title: Trial of Vitamin D in HIV Progression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: Management and Development for Health (MDH)
First posted: 2013-02-26
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the efficacy and safety of vitamin D3 (cholecalciferol) supplementation on HIV progression and incidence of pulmonary tuberculosis among HIV-positive Tanzanian adult men and women initiating highly active antiretroviral therapy (HAART).

Detailed description: HIV-infected adults initiating antiretroviral therapy in resource-limited settings experience high mortality, pulmonary tuberculosis, and other comorbidity rates during the first year of HIV treatment. Observational studies have shown low vitamin D is a risk factor for HIV progression and incidence of pulmonary tuberculosis among adults initiating HAART; however, whether this relationship is causal and if vitamin D supplementation starting at HAART initiation can improve health outcomes has not been determined. This study is a randomized, double-blind, placebo-controlled trial conducted to examine the effect of vitamin D3 supplementation on morality and pulmonary tuberculosis for adults initiating HAART. Participants are HIV-positive Tanzanian men and women aged 18 years and older, who are initiating HAART at the time of randomization whose baseline 25-hydroxyvitamin D (25(OH)D) concentration is \<30ng/mL. Eligible individuals are randomized to receive a) a vitamin D3 regimen consisting 50,000 IU of vitamin D3 taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 supplements taken orally once per day starting at 4 weeks until study discharge at 12 months or b) placebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken daily starting at 4 weeks until study discharge. Participants will be followed for 12 months after ART initiation.

Eligibility criteria: Inclusion Criteria:

* HIV-positive
* Men or Women
* 18 Years of Age or older
* Initiating HAART at time of randomization
* 25(OH)D concentration \<30 ng/mL at HAART initiation

Exclusion Criteria:

* Pregnant Women
* Enrolled in another micronutrient trial

Primary outcomes:
measure: All-cause death
timeFrame: within 12 months after randomization
measure: Pulmonary tuberculosis
timeFrame: within 12 months after randomization
Secondary outcomes:
measure: CD4+ T-cell count
timeFrame: 6 and 12 months after randomization
measure: Physician diagnosis of comorbidities
timeFrame: within 12 months after randomization
measure: Parathyroid hormone (PTH)
timeFrame: 1, 6, and 12 months after randomization
measure: Alkaline phosphatase (ALP)
timeFrame: 1, 6, and 12 months after randomization
measure: >10% weight loss
timeFrame: monthly from month 1 to month 12
measure: Wasting (BMI <18.5 kg/m2)
timeFrame: monthly from month 1 to month 12
measure: Hypercalcemia
timeFrame: 1, 6, and 12 months after randomization
measure: Physical activity
timeFrame: 6 and 12 months after randomization
measure: Immunologic biomarker levels (IL-2, IL-12, IFN-γ, and cathelicidin)
timeFrame: 1, 6, and 12 months after randomization
measure: Depression and anxiety scores
timeFrame: 6 and 12 months after randomization
Other outcomes:
Locations:
city: Dar es Salaam
country: Tanzania
facility: Management and Development for Health (MDH)
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Wafaie W Fawzi, MBBS, DrPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Management and Development for Health (MDH)
name: Ferdinand M Mugusi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sudfeld CR, Mugusi F, Aboud S, Nagu TJ, Wang M, Fawzi WW. Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial. Trials. 2017 Feb 10;18(1):66. doi: 10.1186/s13063-017-1819-5.
citation: Muhihi A, Fawzi WW, Aboud S, Nagu TJ, Ulenga N, Wang M, Mugusi F, Sudfeld CR. Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial. J Nutr. 2022 Aug 9;152(8):1983-1990. doi: 10.1093/jn/nxac096.
citation: Sudfeld CR, Mugusi F, Muhihi A, Aboud S, Nagu TJ, Ulenga N, Hong B, Wang M, Fawzi WW. Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2020 Jul;7(7):e463-e471. doi: 10.1016/S2352-3018(20)30108-9.