Vitamin D Deficiency
Conditions
Brief summary
The proposed study is a randomized, double-blind, controlled, multi-center clinical trial of six months of daily oral vitamin D3 (cholecalciferol). This study will randomize 334 community-dwelling post-menopausal women of European and African descent (\ 167 from each ancestry) in a 1:1 ratio between the control arm and the dosing algorithm arm using stratified block randomization with a block size of six and stratification by site (ancestry). The sample size of 334 includes 10% over-recruitment to allow for loss to follow-up. The European ancestry women will be seen in the Madison clinic and the African ancestry women will be seen in the Milwaukee clinic. The proposed study will focus on post-menopausal women because this is the subset of the population that both Dr. Engelman's and Dr. Binkley's preliminary data are drawn from. Moreover, 25(OH)D concentrations are typically lower in women and in older individuals, since production of vitamin D in the skin following sun exposure decreases with age. Therefore, this group of individuals is likely to benefit the most from vitamin D supplementation, especially when personalized based on biology using the proposed dosing algorithm.
Detailed description
Potential volunteers will be screened by telephone. Those meeting all inclusion and no exclusion criteria will be invited to a screening study visit. At screening, informed consent will be obtained. The study team will then collect the following to determine study eligibility: basic demographic information (age, ancestry, and education); medical history; medication and supplement use; and blood for screening 25(OH)D and calcium tests. At baseline, participants will be randomly assigned to the control or dosing algorithm group. Both participants and study staff who have contact with the participants will be blinded to group assignment. Follow-up visits will occur at three and six months. At baseline and follow-up visits, height and weight will be measured and blood will be drawn for the vitamin D panel, calcium, and PTH. Blood for DNA and body composition will only be obtained at the baseline visit. Participants will be asked to return all unused study supplements and compliance will be assessed at each follow-up visit by pill count. The control group will receive 2500 IU of vitamin D3 daily while the dosing algorithm group will initially receive 1000, 2500, or 4000 IU daily, with the initial dosing based on the 25(OH)D at baseline, and the dosing may be adjusted at the 3-month visit.
Interventions
DIETARY_SUPPLEMENTVitamin D
Gelcaps containing 1000, 2500, and 4000 IU of vitamin D3 will be obtained from Tischon corporation (Westbury, NY). The gelcaps will be protected from light and not stored above 25° C. Participants will be instructed to take their vitamin D3 gelcaps with supper daily. Compliance with study supplementation will be documented by pill count at the time of each study visits.
Sponsors
Medical College of Wisconsin
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
* Healthy, community-dwelling postmenopausal woman of self-reported European (Madison site) or African (Milwaukee site) descent * Able and willing to sign informed consent * Baseline serum 25(OH)D concentration of 10.0-29.9 ng/mL * Willing to not alter the amount of their baseline vitamin D supplementation during the course of this study * Willing to use sunscreen (SPF ≥15) when sun exposure of \>15 minutes is expected during the months of May through September
Exclusion criteria
* Diagnosis of kidney or liver disease (organs that metabolize vitamin D) * Current hypercalcemia (serum calcium ≥ 10.5 mg/dL) or other disorders that may affect vitamin D metabolism and predispose to hypercalcemia, i.e., sarcoidosis, active tuberculosis or other granulomatous disease. * Other chronic diseases or conditions potentially affecting vitamin D metabolism or absorption (inflammatory bowel disease, cystic fibrosis, ulcerative colitis, and malabsorptive surgery) * History of nephrolithiasis * Current use of medications that affect vitamin D metabolism (glucocorticoids, anticonvulsants, antifungals, and HIV/AIDS medications) * History of any form of cancer within the past two years with the exception of basal or squamous cell skin lesions, in situ tumors or thyroid cancer * Terminal illness/on hospice * Severe end-organ disease (e.g., cardiovascular, pulmonary, etc.), which may limit the ability to complete the study * Treatment with high dose vitamin D (≥50,000 IU weekly) or any active metabolites of vitamin D, e.g., calcitriol, within six months of screening; current use of multiple vitamins and other vitamin D supplements will be allowed. * Use of tanning beds or salons or unwillingness to utilize sunscreen during periods of sun exposure of 15 minutes or longer from May through September * Planned trips/vacations likely to be associated with substantial amounts of sun exposure during the course of the study (i.e., more than 500 miles south of Madison/Milwaukee)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of the Dosing Algorithm in Achieving Total 25(OH)D as Measured by the Percentage of Participants Ending With Concentrations of 35-50 ng/mL | 3 and 6 months | To validate the proposed vitamin D3 dosing algorithm, a vitamin D panel consisting of serum concentrations of vitamin D3 (cholecalciferol; an indicator of vitamin D3 absorption), 25(OH)D3, 25(OH)D2, the C3-epimer of 25(OH)D3 and 24,25(OH)2D as well as an assay to directly measure free serum 25(OH)D will be run on all the blood samples collected at the baseline, 3 month and 6 month visits. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group The control group will receive 2500 IU of vitamin D3 daily.
Vitamin D: Gelcaps containing 1000, 2500, and 4000 IU of vitamin D3 will be obtained from Tischon corporation (Westbury, NY). The gelcaps will be protected from light and not stored above 25° C. Participants will be instructed to take their vitamin D3 gelcaps with supper daily. Compliance with study supplementation will be documented by pill count at the time of each study visits. | 83 |
| Dosing Algorithm Group The dosing algorithm group will initially receive 1000, 2500, or 4000 IU of vitamin D3 daily based on the baseline 25(OH)D. This group's dosing may be adjusted at the 3-month visit.
Vitamin D: Gelcaps containing 1000, 2500, and 4000 IU of vitamin D3 will be obtained from Tischon corporation (Westbury, NY). The gelcaps will be protected from light and not stored above 25° C. Participants will be instructed to take their vitamin D3 gelcaps with supper daily. Compliance with study supplementation will be documented by pill count at the time of each study visits. | 86 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 6 |
| Overall Study | Moved | 1 | 0 |
Baseline characteristics
| Characteristic | Control Group | Dosing Algorithm Group | Total |
|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 10.9 | 63.6 years STANDARD_DEVIATION 6.7 | 63.5 years STANDARD_DEVIATION 7.5 |
| Baseline 25(OH)Vitamin D | 26.4 ng/mL STANDARD_DEVIATION 7.5 | 27.8 ng/mL STANDARD_DEVIATION 7.6 | 27.0 ng/mL STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 86 Participants | 168 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 15 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 69 Participants | 71 Participants | 140 Participants |
| Sex: Female, Male Female | 83 Participants | 86 Participants | 169 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 / 82 | 0 / 80 |
| other Total, other adverse events | 0 / 82 | 0 / 80 |
| serious Total, serious adverse events | 2 / 82 | 3 / 80 |
Outcome results
Primary
Efficacy of the Dosing Algorithm in Achieving Total 25(OH)D as Measured by the Percentage of Participants Ending With Concentrations of 35-50 ng/mL
To validate the proposed vitamin D3 dosing algorithm, a vitamin D panel consisting of serum concentrations of vitamin D3 (cholecalciferol; an indicator of vitamin D3 absorption), 25(OH)D3, 25(OH)D2, the C3-epimer of 25(OH)D3 and 24,25(OH)2D as well as an assay to directly measure free serum 25(OH)D will be run on all the blood samples collected at the baseline, 3 month and 6 month visits.
Time frame: 3 and 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Group | Efficacy of the Dosing Algorithm in Achieving Total 25(OH)D as Measured by the Percentage of Participants Ending With Concentrations of 35-50 ng/mL | 3 Months | 61.3 percentage of participants in goal range |
| Control Group | Efficacy of the Dosing Algorithm in Achieving Total 25(OH)D as Measured by the Percentage of Participants Ending With Concentrations of 35-50 ng/mL | 6 Months | 47.6 percentage of participants in goal range |
| Dosing Algorithm Group | Efficacy of the Dosing Algorithm in Achieving Total 25(OH)D as Measured by the Percentage of Participants Ending With Concentrations of 35-50 ng/mL | 3 Months | 58.5 percentage of participants in goal range |
| Dosing Algorithm Group | Efficacy of the Dosing Algorithm in Achieving Total 25(OH)D as Measured by the Percentage of Participants Ending With Concentrations of 35-50 ng/mL | 6 Months | 50.3 percentage of participants in goal range |