A New Paradigm for Vitamin D Sufficiency

NCT ID: NCT02969850

Last Updated: 2021-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

444 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2019-12-01

Brief Summary

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Although the African-American (AA) population tends to have lower serum 25(OH)D levels compared to whites, there is no evidence that the lower 25(OH)D levels in African-Americans are harmful. In fact, skeletal health is superior in AA. It is clear that total serum 25(OH)D concentrations do not reflect the same risk/benefit ratio in AA compared to white women and is, therefore, an inappropriate biomarker in this population.

The investigators wish to investigate whether free 25(OD)D and Vitamin D Metabolite Ratio (VMR, ratio of 25(OH)D to 24,25(OH)2D) are preferable biomarkers to total 25(OH)D. The investigators propose a six month randomized double blinded study.

Detailed Description

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The specific aims of this study are as follows:

1. To establish that free 25(OH)D and VMR are similar in black and white populations.
2. To characterize the relationships between free 25(OH)D and VMR and two measures of bone health (PTH and BMD) in black and white women.
3. To evaluate whether the relationship of free 25(OH)D (and in parallel analyses, VMR) and bone health are stronger than those based on total 25(OH)D.
4. To evaluate whether free 25(OH)D and VMR respond to vitamin D intake (dose-response) in a similar manner to total 25(OH)D.

The study population is postmenopausal Caucasian women age 60 and older. This six month study includes four visits. These results will be compared to those from a study in AA women which the investigators are also completing.

There are two study groups. One group will receive vitamin D supplementation, the other a placebo. Subjects will be asked to refrain from taking outside Vitamin D supplements for the duration of the study. If the subject is eligible based on the results from the first two visits, the subject will be randomized into one of these two groups. Randomized subjects will be taking the vitamin D or placebo for a period of 6 months and will have one visit at the 3 month mark and a final visit at the 6 month mark.

At the 3-month visit, the following procedures will be conducted: obtain interim medical and travel history, vital signs, weight, and height measured by the Harpenden Stadiometer, record adverse events and concomitant medications, Fasting blood collection: total 25(OH)D (by Diasorin), PTH, serum calcium and creatinine, Fasting urine collection for calcium and creatinine, and questionnaires: calcium food frequency questionnaire, quality of life questionnaire, falls and flu questionnaires. Subjects will be instructed on how to collect a 24-hour urine sample (for final visit) and collection container will be dispensed. Unused study supplements will be collected and counted, and study supplements will be dispensed based on serum 25(OH)D level algorithm.

At the 6-month visit, in addition to what is completed at the 3-month visit, the following procedures will also be conducted:24-hour urine calcium, sodium, oxalate and creatinine; mini-mental health examination; physical performance examination (SPPB); and a physical activity questionnaire. Unused study supplements will be collected and counted. No further supplementation will be provided.

Conditions

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New Biomarkers for Measuring Vitamin D Level

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vitamin D Supplementation

Participant will receive initial dose of 2400, 3600, or 4800 IU of vitamin D3, based on her serum vitamin D level. Dose will be adjusted at 3 month visit to maintain serum vitamin D level at a desirable level. If subject has insufficient dietary calcium intake, calcium supplementation will be provided in the form of one 600mg CaCO3 pill to achieve a total calcium intake of 1200mg/day.

Group Type EXPERIMENTAL

Vitamin D Supplementation

Intervention Type DIETARY_SUPPLEMENT

Subjects in this group will receive initial dose of 2400, 3600, or 4800 IU of vitamin D3, based on her serum vitamin D level. Dose will be adjusted at 3 month visit to maintain serum vitamin D level at a desirable level.

Calcium

Intervention Type DIETARY_SUPPLEMENT

If dietary calcium intake is insufficient in participants of either group, they will be given a calcium supplement in the form of one 600mg pill of CaCO3 to bring them up to an intake of 1200mg/day.

Placebo

Participant will receive a placebo. If subject has insufficient dietary calcium intake, calcium supplementation will be provided in the form of one 600mg CaCO3 pill to achieve a total calcium intake of 1200mg/day.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Subjects in this group will receive a placebo.

Calcium

Intervention Type DIETARY_SUPPLEMENT

If dietary calcium intake is insufficient in participants of either group, they will be given a calcium supplement in the form of one 600mg pill of CaCO3 to bring them up to an intake of 1200mg/day.

Interventions

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Vitamin D Supplementation

Subjects in this group will receive initial dose of 2400, 3600, or 4800 IU of vitamin D3, based on her serum vitamin D level. Dose will be adjusted at 3 month visit to maintain serum vitamin D level at a desirable level.

Intervention Type DIETARY_SUPPLEMENT

Placebo

Subjects in this group will receive a placebo.

Intervention Type OTHER

Calcium

If dietary calcium intake is insufficient in participants of either group, they will be given a calcium supplement in the form of one 600mg pill of CaCO3 to bring them up to an intake of 1200mg/day.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

1. Ambulatory women older than 60 years of age. Women who are ambulatory with an assistive device such as cane or walker may be included. LMP must be \> 5 years ago.
2. Self declared as white.
3. 20 nmol/L \< Serum 25(OH)D level \< 65 nmol/L.
4. Willingness to take study drug and participate for 6 months in the trial.
5. Willingness to refrain from the use of self-administered Vitamin D and Calcium supplements during the trial.

Exclusion Criteria

1. Serum 25(OH)D levels ≤ 20 nmol/L or ≥ 65 nmol/L.
2. BMD total hip below -2.5 standard deviation (using NHANES III adult young white men and women as the point of reference) or history of osteoporotic fracture.
3. Moderate to severe fracture in one or more vertebrae by Instant Vertebral Assessment on DXA.
4. Treatment with HRT, SERMs, calcitonin, PTH, strontium ranelate, androgens, bisphosphonates, Denosumab or anabolic steroids during 6 months prior to entry.
5. Use of systemic corticosteroids (oral or IV) within the last year at an average dose of greater than 5 mg per day of oral prednisone or equivalent for a period of three months or more prior to screening.
6. Mini-Mental State Exam score below 21
7. Hypercalcemia (serum calcium \> 10.6 mg/dl) or history of primary hyperparathyroidism.
8. History of hypercalciuria, kidney stones, or 24hr urine calcium \>261 mg/day on screening.
9. History of chronic liver disease, chronic renal insufficiency (GFR\<30), Parkinson's, metabolic bone disease (Hyperparathyroidism, Hypoparathyroidism, Paget's disease, Fibrous osteodystrophy, Rickets, Osteomalacia, Osteosclerosis), hematologic tumors, rheumatologic disease requiring steroids, conditions that influence vitamin D absorption like celiac disease and irritable bowel disease, malabsorption or new diagnosis or active treatment of cancer 12 months prior to inclusion.
10. Use of medications that influence bone metabolism (e.g. anticonvulsants).
11. Significant deviation from normal in either: history, physical examination or laboratory tests as evaluated by the Principle Investigator. Participants with a history of uncontrolled hypertension, uncontrolled diabetes, hypercalciuria, nephrolithiasis and active sarcoidosis or tuberculosis will also be excluded.
12. Participation in another investigational trial 30 days prior to screening.
13. Spinal disease that affects interpretation of bone densitometry like scoliosis with a Cobb angle greater than 15o, history of surgery at lumbosacral spine.
14. Bilateral hip replacement.
15. Currently smoking more than 10 cigarettes daily.
16. Currently consuming more than 2 units of alcohol daily. (One unit is equivalent to a standard glass of beer (285ml), a single measure of spirits (30ml), a medium-sized glass of wine (120ml), or 1 measure of an aperitif (60ml)
17. Unable to perform DXA due to excessive body girth/width. Body width on DXA \> 25 cm.
18. Patients who are deemed unsafe to perform muscular function testing as evaluated by the investigator.
19. Class III obesity.
Minimum Eligible Age

60 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Winthrop University Hospital

OTHER

Sponsor Role collaborator

NYU Langone Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Aloia, MD

Role: PRINCIPAL_INVESTIGATOR

Winthrop University Hospital

Mageda Mikhail, MD

Role: STUDY_DIRECTOR

Winthrop University Hospital

Locations

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Winthrop University Hospital

Mineola, New York, United States

Site Status

Countries

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United States

Other Identifiers

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19-00873

Identifier Type: -

Identifier Source: org_study_id