Effect of Vitamin D Supplementation on Bone Turnover Markers During PrEP in MSM

Study Overview
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Brief Summary
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CCTG 595 is an open-label clinical trial of the effect of a text messaging intervention vs. standard of care on adherence to Truvada as PrEP in MSM at increased risk for HIV infection (ClinicalTrials.gov Identifier: NCT01761643). Eligible subjects for this matched case control substudy will receive vitamin D 4000 IU/day for 24 weeks, from week 24 through week 48. In CCTG 595, plasma from participants are being collected and stored at entry and every 12 weeks. These plasma samples will be used to measure P1NP, CTX, PTH, and vitamin D levels in both cases and controls at entry, week 24, and week 48.

Detailed Description
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A total of 50 HIV-uninfected men who have sex with men (MSM) and male to female (M to F) transgender individuals already enrolled in CCTG 595 will be offered participation in the sub-study at Week 24 of the main study. All subjects enrolled into the sub-study will be provided Vitamin D 4000 IU/day supplements in addition to their PrEP at Weeks 24 and 36; clinic visits will proceed normally per main study protocol. Upon completion of the sub-study subjects will continue on the main study. The primary endpoint, bone turnover markers, will be measured from Week 24 to Week 48 via plasma samples collected through the main study. Concurrent controls who are not enrolled in the vitamin D substudy who are reporting supplementation with < 400 IU of vitamin D/day will be matched 1:1 by randomization arm in the CCTG 595 main study (text messaging arm vs. standard of care), age (± 5 years), race/ethnicity, season of study entry, and BMI (± 3 kg/m2).

Official Title
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Effect of Vitamin D Supplementation on Bone Turnover Markers During Tenofovir-Emtricitibine Pre-Exposure Prophylaxis in Men Who Have Sex With Men; A Sub-study of CCTG 595

Conditions
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Patient Adherence

Intervention / Treatment
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* Drug: Vitamin D Supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must meet CCTG 595 inclusion criteria. Exclusion Criteria: All subjects must meet CCTG 595 exclusion criteria. Current or prior use of bisphosphonate therapy. Current use of Vitamin D supplements greater than 400 IU/day. Current use of androgenic hormones or growth hormones. History of nephrolithiasis (kidney stones). History of fragility fracture. No use of tenofovir prior to entry into CCTG 595

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D Supplement + PrEP<br>Subjects enrolled into this sub-study will be provided Vitamin D 4000IU/day for 24 Weeks in addition to their PrEP provided through the main study. | Drug: Vitamin D Supplement<br>* Subjects enrolled into this sub-study will be provided Vitamin D 4000IU/day for 24 Weeks.<br>|
| No Intervention: PrEP Only<br>Subjects not enrolled into this sub-study will continue receiving PrEP through the main study. Subjects taking unsupplemented PrEP may still be used as matched controls to sub-study subjects. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Procollagen Type 1 N-terminal Propeptide (a Marker of Bone Formation) [P1NP] Levels | To compare the change in P1NP levels from Week 24 through Week 48 among subjects (cases) who receive vitamin D 4000 IU/day to the change in levels seen in matched unsupplemented controls | Weeks 24-48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CTX-1 Levels | To compare the change in CTX-1 levels from Week 24 through Week 48 among subjects (cases) who receive vitamin D 4000 IU/day to the change in levels seen in matched unsupplemented controls | Weeks 24-48 | 
| Change in PTH Levels | To compare the change in PTH levels from Week 24 through Week 48 among subjects (cases) who receive vitamin D 4000 IU/day to the change in levels seen in matched unsupplemented controls | Weeks 24-48 | 
| Change in 25-OH Vitamin D3 Levels | To compare the change in 25-OH vitamin D3 levels from Week 24 through Week 48 among subjects (cases) who receive vitamin D 4000 IU/day to the change in levels seen in matched unsupplemented controls | Weeks 24-48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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595, PrEP, Pre exposure Prophylaxis, Truvada, CCTG, Vitamin D, Bone mineral density