HIV InfectionPhase 3TOV4NCT01798680
Trial of Vitamin D in HIV Progression
A Phase 3 study testing Vitamin D3 (cholecalciferol) in people with HIV Infection, run by Harvard School of Public Health (HSPH) at 1 site in Tanzania.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Vitamin D3 (cholecalciferol)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,000 participants
- Where
- 1 siteTanzania
- Study dates
- Feb 2014to 31 Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Pregnant Women
- Enrolled in another micronutrient trial
Trial locations and contacts
1 site in 1 country.
About this study
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).
Read the 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.
- Conditions
- HIV Infection
- Being tested
- Vitamin D3 (cholecalciferol), Placebo
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3 (cholecalciferol)Dietary supplement
Supplements containing 50,000 IU of vitamin D3 (cholecalciferol) taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 (cholecalciferol) supplements taken orally once per day starting at 4 weeks until study discharge at 12 months
PlaceboOther
Placebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken orally once per day starting at 4 weeks until study discharge at 12 months
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D3 (cholecalciferol) | Experimental | Not described Receives: Dietary Supplement: Vitamin D3 (cholecalciferol) |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause death
Measured: within 12 months after randomization
Pulmonary tuberculosis
Measured: within 12 months after randomization
Secondary outcomes (10)
CD4+ T-cell count
Measured: 6 and 12 months after randomization
Physician diagnosis of comorbidities
Measured: within 12 months after randomization
Parathyroid hormone (PTH)
Measured: 1, 6, and 12 months after randomization
Alkaline phosphatase (ALP)
Measured: 1, 6, and 12 months after randomization
>10% weight loss
Measured: monthly from month 1 to month 12
Wasting (BMI <18.5 kg/m2)
Measured: monthly from month 1 to month 12
Hypercalcemia
Measured: 1, 6, and 12 months after randomization
Physical activity
Measured: 6 and 12 months after randomization
Immunologic biomarker levels (IL-2, IL-12, IFN-γ, and cathelicidin)
Measured: 1, 6, and 12 months after randomization
Depression and anxiety scores
Measured: 6 and 12 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startFeb 2014
- Primary completionMar 2018
- Study completion31 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harvard School of Public Health (HSPH)
- Sponsor type
- University, hospital or other
- Collaborators
- Management and Development for Health (MDH)
- Responsible party
- Principal investigator, Wafaie Fawzi, Harvard School of Public Health (HSPH)
- Investigators
- Wafaie W Fawzi, MBBS, DrPH, Principal investigator, Harvard School of Public Health (HSPH)Ferdinand M Mugusi, MD, Principal investigator, Management and Development for Health (MDH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01798680
- Sponsor's protocol ID
- R01DK098075
- Acronym
- TOV4
- Status last verified
- Aug 2019
- First submitted
- 21 Feb 2013
- Last updated
- 9 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 28183335Muhihi 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.
PubMed 35460249Sudfeld 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.
PubMed 32621874
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Vitamin D in HIV Progression
- ClinicalTrials.gov ID
- NCT01798680
- Acronym / sponsor ID
- TOV4 / R01DK098075
- Conditions
- HIV Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,000 participants (actual)
- Lead sponsor
- Harvard School of Public Health (HSPH)University, hospital or other
- Collaborators
- Management and Development for Health (MDH)
- Study start
- Feb 2014 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 26 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D3 (cholecalciferol) | Experimental | Dietary Supplement: Vitamin D3 (cholecalciferol) |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- Pregnant Women
- Enrolled in another micronutrient trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3 (cholecalciferol)Supplements containing 50,000 IU of vitamin D3 (cholecalciferol) taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 (cholecalciferol) supplements taken orally once per day starting at 4 weeks until study discharge at 12 months | Dietary supplement | Vitamin D3 (cholecalciferol) |
| PlaceboPlacebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken orally once per day starting at 4 weeks until study discharge at 12 months | Other | Placebo |
Primary outcome
All-cause death
Time frame: within 12 months after randomization
Pulmonary tuberculosis
Time frame: within 12 months after randomization
10 secondary outcomes
CD4+ T-cell count
Time frame: 6 and 12 months after randomization
Physician diagnosis of comorbidities
Time frame: within 12 months after randomization
Parathyroid hormone (PTH)
Time frame: 1, 6, and 12 months after randomization
Alkaline phosphatase (ALP)
Time frame: 1, 6, and 12 months after randomization
>10% weight loss
Time frame: monthly from month 1 to month 12
Wasting (BMI <18.5 kg/m2)
Time frame: monthly from month 1 to month 12
Hypercalcemia
Time frame: 1, 6, and 12 months after randomization
Physical activity
Time frame: 6 and 12 months after randomization
Immunologic biomarker levels (IL-2, IL-12, IFN-γ, and cathelicidin)
Time frame: 1, 6, and 12 months after randomization
Depression and anxiety scores
Time frame: 6 and 12 months after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2019.
- Background: PubMed 28183335Sudfeld 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.
- Derived from this study: PubMed 35460249Muhihi 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.
- Derived from this study: PubMed 32621874Sudfeld 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wafaie W Fawzi, MBBS, DrPH principal investigator
Harvard School of Public Health (HSPH)
Ferdinand M Mugusi, MD principal investigator
Management and Development for Health (MDH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D3 (cholecalciferol) in people with HIV Infection, run by Harvard School of Public Health (HSPH) at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause death (time frame: within 12 months after randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01798680, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2019.