HIV
Conditions
Keywords
HIV, Postmenopausal women, Vitamin D
Brief summary
The purpose of this study is to determine the effects of vitamin D on measures of bone health and immune function in HIV infected postmenopausal women. The investigators prior research with this population revealed that low vitamin D levels are very common. Prior research with this population also revealed that Vitamin D is necessary for the body to absorb calcium and is important for the health of the bones. When vitamin D levels are low, there are increased risks of bone loss, muscle weakness, falls and fractures. Low levels of vitamin D have also been associated with impaired immune function. This study will help us learn whether two different doses of vitamin D will improve bone health and immune function.
Detailed description
The purpose of this study is to determine the effects of vitamin D repletion on rates of bone loss and indices of immune function in HIV+ postmenopausal women. Lower baseline serum Vitamin D levels, as assessed by measuring serum 25-hydroxyvitamin D (25-OHD) were associated with a trend toward more bone loss. In addition, the investigators found that despite providing supplements that contained approximately 600 IU vitamin D, serum 25-OHD did not increase during the first year. Provision of adequate calcium and vitamin D is the cornerstone of effective prevention and therapy of osteoporosis. HIV-infected patients may be at increased risk of having vitamin D deficiency because they take several medications that may interfere with vitamin D action. Therefore, the investigators will recruit 100 HIV infected postmenopausal women for this study who are on a stable antiretroviral therapy (ART) regimen and randomize them to receive 1000 or 3000 IU of vitamin D daily. The subjects will be followed closely for one year to monitor compliance and changes in bone health and immune function.
Interventions
DRUGVitamin D3
2000 mg QD
OTHERPlacebo
An inactive treatment that is intended to provide baseline measurements for the experimental protocol of a clinical trial, in this case, the vitamin D3.
Specially formulated supplements (Tishcon, Inc.) that contain 500 mg of calcium (carbonate) and 500 IU of vitamin D3 to be taken twice daily with breakfast and dinner (1000 mg of elemental calcium and 1000 IU of vitamin D).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* HIV+ African American and Latina postmenopausal women, aged 40-70, who meet the standard definition of menopause: If 50 years old or older then amenorrhea for \> 1year. If age 40 to 49 then amenorrhea for over a year and and Follicle-Stimulating Hormone (FSH) level of equal to or greater than 20 mIU/ml; as some amenorrheic chronically ill women may have hypothalamic dysfunction and low FSH values, if FSH is 10 to 19, and the serum estradiol level is consistent with menopause less than or equal to 30pg/ml, she will be determined to be postmenopausal. * On stable antiretroviral therapy (ART) for \>2 years * Undetectable HIV RNA (viral load) at least 2 times over the past year (RNA \<400)
Exclusion criteria
* Metabolic bone disease (Paget's disease, clinical osteomalacia, primary hyperparathyroidism, hypercalcemia) * Multiple myeloma, solid tumors with metastases; * Endocrinopathy (hyperthyroidism, untreated hypothyroidism, Cushing's syndrome, prolactin-secreting pituitary adenoma) * Renal insufficiency (serum creatinine above 1.5 mg/dl) * Liver disease (AST, ALT, bilirubin, total alkaline phosphatase activity \> twice upper normal limit); * Intestinal disorders (celiac disease, pancreatic insufficiency, Crohn's disease, ulcerative colitis) * Current use of glucocorticoids, anticonvulsants, anticoagulants, diuretics, methotrexate; * Current or past use of drug therapies for osteoporosis (raloxifene, bisphosphonates, calcitonin, PTH). Women on estrogen are excluded. Past estrogen use is permitted if discontinued \>1 year before enrollment. * If there is a history of a low trauma fracture, a T score \< -3 or a prevalent vertebral fracture on Instant Vertebral Assessment™ (IVA), subjects will be referred for osteoporosis treatment as appropriate. * Severe vitamin D deficiency (25-OHD level \<10 ng/ml) or normal baseline serum vitamin D (25-OHD \>32 ng/ml). Subjects with severe vitamin D deficiency may be referred to our sub-study, if all other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bone Mineral Density (BMD) | Baseline, 12 months | Percent change from baseline in BMD at lumbar spine (as measured by Dual-emission X-ray absorptiometry (DXA) scan) at 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Areal Change in Bone Mineral Density (aBMD) | Baseline,12 months | To evaluate the change in areal BMD (aBMD) at the total hip (TH) |
| Change in Volumetric Bone Mineral Density (vBMD) | Baseline, 12 months | To evaluate the change in volumetric BMD (VBMD) at the Tibia |
| Change in Vitamin D Levels | 12 months | To evaluate the change in vitamin D levels with supplementation |
| Change in Biochemical Markers | 12 months | To evaluate the effect of vitamin D and calcium supplementation on biochemical markers of bone turnover and markers of inflammation. (PTH) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Placebo vitamin D3 capsule daily plus vitamin supplements that contains 1000 IU vitamin D3 and 1000 mg calcium carbonate daily. Total daily vitamin D3 dose = 1000 IU.
Placebo: An inactive treatment that is intended to provide baseline measurements for the experimental protocol of a clinical trial, in this case, the vitamin D3.
Vitamin Supplements: Specially formulated supplements (Tishcon, Inc.) that contain 500 mg of calcium (carbonate) and 500 IU of vitamin D3 to be taken twice daily with breakfast and dinner (1000 mg of elemental calcium and 1000 IU of vitamin D). | 43 |
| Group B 2000 IU vitamin D3 daily plus vitamin supplements that contains 1000 IU vitamin D3 and 1000 mg calcium carbonate daily. Total daily vitamin D3 dose = 3000 IU.
Vitamin D3: 2000 mg QD
Vitamin Supplements: Specially formulated supplements (Tishcon, Inc.) that contain 500 mg of calcium (carbonate) and 500 IU of vitamin D3 to be taken twice daily with breakfast and dinner (1000 mg of elemental calcium and 1000 IU of vitamin D). | 42 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Group B | Total | Group A |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 5.6 | 56.3 years STANDARD_DEVIATION 5.2 | 56.2 years STANDARD_DEVIATION 4.9 |
| Race/Ethnicity, Customized African American | 20 Participants | 37 Participants | 17 Participants |
| Race/Ethnicity, Customized Hispanic | 22 Participants | 48 Participants | 26 Participants |
| Sex: Female, Male Female | 42 Participants | 85 Participants | 43 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 42 |
| other Total, other adverse events | 6 / 43 | 5 / 42 |
| serious Total, serious adverse events | 1 / 43 | 1 / 42 |
Outcome results
Primary
Change in Bone Mineral Density (BMD)
Percent change from baseline in BMD at lumbar spine (as measured by Dual-emission X-ray absorptiometry (DXA) scan) at 12 months
Time frame: Baseline, 12 months
Population: A complete case approach was utilized for outcome in participants with BMD data at 12 months (n=69).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Change in Bone Mineral Density (BMD) | 0.4 percentage change | Standard Deviation 4.4 |
| Group B | Change in Bone Mineral Density (BMD) | -0.8 percentage change | Standard Deviation 4.6 |
Secondary
Areal Change in Bone Mineral Density (aBMD)
To evaluate the change in areal BMD (aBMD) at the total hip (TH)
Time frame: Baseline,12 months
Population: A complete case approach was utilized for outcome in participants with BMD data at 12 months (n=69).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Areal Change in Bone Mineral Density (aBMD) | -0.5 percentage of change | Standard Deviation 3.1 |
| Group B | Areal Change in Bone Mineral Density (aBMD) | -0.8 percentage of change | Standard Deviation 3.2 |
Secondary
Change in Biochemical Markers
To evaluate the effect of vitamin D and calcium supplementation on biochemical markers of bone turnover and markers of inflammation. (PTH)
Time frame: 12 months
Population: A complete case approach was utilized for secondary outcomes in participants with data at 12 months (n=69).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Change in Biochemical Markers | -7.2 percentage of change | Standard Deviation 71.4 |
| Group B | Change in Biochemical Markers | -16.8 percentage of change | Standard Deviation 33 |
Secondary
Change in Vitamin D Levels
To evaluate the change in vitamin D levels with supplementation
Time frame: 12 months
Population: A complete case approach was utilized for secondary outcomes in participants with data at 12 months (n=69).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Change in Vitamin D Levels | 33.7 percentage of change | Standard Deviation 41.9 |
| Group B | Change in Vitamin D Levels | 64.1 percentage of change | Standard Deviation 68.6 |
Secondary
Change in Volumetric Bone Mineral Density (vBMD)
To evaluate the change in volumetric BMD (VBMD) at the Tibia
Time frame: Baseline, 12 months
Population: A complete case approach was utilized for secondary outcomes in participants with vBMD data at 12 months (n=69).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Change in Volumetric Bone Mineral Density (vBMD) | -0.3 percentage of change | Standard Deviation 2.9 |
| Group B | Change in Volumetric Bone Mineral Density (vBMD) | -0.9 percentage of change | Standard Deviation 2.5 |