<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02969850</url>
  </required_header>
  <id_info>
    <org_study_id>19-00873</org_study_id>
    <nct_id>NCT02969850</nct_id>
  </id_info>
  <brief_title>A New Paradigm for Vitamin D Sufficiency</brief_title>
  <official_title>A New Paradigm for Vitamin D Sufficiency: A 6-month, Randomized, Double-blind, Placebo-controlled Study to Investigate Vitamin D Status in Elderly Caucasian Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Winthrop University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although the African-American (AA) population tends to have lower serum 25(OH)D levels&#xD;
      compared to whites, there is no evidence that the lower 25(OH)D levels in African-Americans&#xD;
      are harmful. In fact, skeletal health is superior in AA. It is clear that total serum 25(OH)D&#xD;
      concentrations do not reflect the same risk/benefit ratio in AA compared to white women and&#xD;
      is, therefore, an inappropriate biomarker in this population.&#xD;
&#xD;
      The investigators wish to investigate whether free 25(OD)D and Vitamin D Metabolite Ratio&#xD;
      (VMR, ratio of 25(OH)D to 24,25(OH)2D) are preferable biomarkers to total 25(OH)D. The&#xD;
      investigators propose a six month randomized double blinded study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aims of this study are as follows:&#xD;
&#xD;
        1. To establish that free 25(OH)D and VMR are similar in black and white populations.&#xD;
&#xD;
        2. To characterize the relationships between free 25(OH)D and VMR and two measures of bone&#xD;
           health (PTH and BMD) in black and white women.&#xD;
&#xD;
        3. To evaluate whether the relationship of free 25(OH)D (and in parallel analyses, VMR) and&#xD;
           bone health are stronger than those based on total 25(OH)D.&#xD;
&#xD;
        4. To evaluate whether free 25(OH)D and VMR respond to vitamin D intake (dose-response) in&#xD;
           a similar manner to total 25(OH)D.&#xD;
&#xD;
      The study population is postmenopausal Caucasian women age 60 and older. This six month study&#xD;
      includes four visits. These results will be compared to those from a study in AA women which&#xD;
      the investigators are also completing.&#xD;
&#xD;
      There are two study groups. One group will receive vitamin D supplementation, the other a&#xD;
      placebo. Subjects will be asked to refrain from taking outside Vitamin D supplements for the&#xD;
      duration of the study. If the subject is eligible based on the results from the first two&#xD;
      visits, the subject will be randomized into one of these two groups. Randomized subjects will&#xD;
      be taking the vitamin D or placebo for a period of 6 months and will have one visit at the 3&#xD;
      month mark and a final visit at the 6 month mark.&#xD;
&#xD;
      At the 3-month visit, the following procedures will be conducted: obtain interim medical and&#xD;
      travel history, vital signs, weight, and height measured by the Harpenden Stadiometer, record&#xD;
      adverse events and concomitant medications, Fasting blood collection: total 25(OH)D (by&#xD;
      Diasorin), PTH, serum calcium and creatinine, Fasting urine collection for calcium and&#xD;
      creatinine, and questionnaires: calcium food frequency questionnaire, quality of life&#xD;
      questionnaire, falls and flu questionnaires. Subjects will be instructed on how to collect a&#xD;
      24-hour urine sample (for final visit) and collection container will be dispensed. Unused&#xD;
      study supplements will be collected and counted, and study supplements will be dispensed&#xD;
      based on serum 25(OH)D level algorithm.&#xD;
&#xD;
      At the 6-month visit, in addition to what is completed at the 3-month visit, the following&#xD;
      procedures will also be conducted:24-hour urine calcium, sodium, oxalate and creatinine;&#xD;
      mini-mental health examination; physical performance examination (SPPB); and a physical&#xD;
      activity questionnaire. Unused study supplements will be collected and counted. No further&#xD;
      supplementation will be provided.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2016</start_date>
  <completion_date type="Actual">December 1, 2019</completion_date>
  <primary_completion_date type="Actual">December 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Compare free 25(OH)D levels in Caucasian women (current study) and AA women (from prior study)</measure>
    <time_frame>baseline</time_frame>
    <description>VDBP will be measured and free 25(OH)D calculated</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Compare Vitamin D metabolite ratio (VMR) in Caucasian women (current study) and AA women (from prior study)</measure>
    <time_frame>baseline</time_frame>
    <description>serum 24,25(OH)2D and serum 25(OH)D will be measured and VMR calculated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relationship between free 25(OH)D and two measures of bone health (PTH and BMD)</measure>
    <time_frame>baseline</time_frame>
    <description>Relationships will be assessed via correlation and regression analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between VMR and two measures of bone health (PTH and BMD)</measure>
    <time_frame>baseline</time_frame>
    <description>Relationships will be assessed via correlation and regression analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between vitamin D intake and Change in Physical Performance Assessment (SPPB)</measure>
    <time_frame>baseline and 6 months</time_frame>
    <description>Relationships will be assessed via Mixed-Effects Model for Repeated Measures (MMRM)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">444</enrollment>
  <condition>New Biomarkers for Measuring Vitamin D Level</condition>
  <arm_group>
    <arm_group_label>Vitamin D Supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D Supplementation</intervention_name>
    <description>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.</description>
    <arm_group_label>Vitamin D Supplementation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects in this group will receive a placebo.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Calcium</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Vitamin D Supplementation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ambulatory women older than 60 years of age. Women who are ambulatory with an&#xD;
             assistive device such as cane or walker may be included. LMP must be &gt; 5 years ago.&#xD;
&#xD;
          2. Self declared as white.&#xD;
&#xD;
          3. 20 nmol/L &lt; Serum 25(OH)D level &lt; 65 nmol/L.&#xD;
&#xD;
          4. Willingness to take study drug and participate for 6 months in the trial.&#xD;
&#xD;
          5. Willingness to refrain from the use of self-administered Vitamin D and Calcium&#xD;
             supplements during the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serum 25(OH)D levels ≤ 20 nmol/L or ≥ 65 nmol/L.&#xD;
&#xD;
          2. BMD total hip below -2.5 standard deviation (using NHANES III adult young white men&#xD;
             and women as the point of reference) or history of osteoporotic fracture.&#xD;
&#xD;
          3. Moderate to severe fracture in one or more vertebrae by Instant Vertebral Assessment&#xD;
             on DXA.&#xD;
&#xD;
          4. Treatment with HRT, SERMs, calcitonin, PTH, strontium ranelate, androgens,&#xD;
             bisphosphonates, Denosumab or anabolic steroids during 6 months prior to entry.&#xD;
&#xD;
          5. Use of systemic corticosteroids (oral or IV) within the last year at an average dose&#xD;
             of greater than 5 mg per day of oral prednisone or equivalent for a period of three&#xD;
             months or more prior to screening.&#xD;
&#xD;
          6. Mini-Mental State Exam score below 21&#xD;
&#xD;
          7. Hypercalcemia (serum calcium &gt; 10.6 mg/dl) or history of primary hyperparathyroidism.&#xD;
&#xD;
          8. History of hypercalciuria, kidney stones, or 24hr urine calcium &gt;261 mg/day on&#xD;
             screening.&#xD;
&#xD;
          9. History of chronic liver disease, chronic renal insufficiency (GFR&lt;30), Parkinson's,&#xD;
             metabolic bone disease (Hyperparathyroidism, Hypoparathyroidism, Paget's disease,&#xD;
             Fibrous osteodystrophy, Rickets, Osteomalacia, Osteosclerosis), hematologic tumors,&#xD;
             rheumatologic disease requiring steroids, conditions that influence vitamin D&#xD;
             absorption like celiac disease and irritable bowel disease, malabsorption or new&#xD;
             diagnosis or active treatment of cancer 12 months prior to inclusion.&#xD;
&#xD;
         10. Use of medications that influence bone metabolism (e.g. anticonvulsants).&#xD;
&#xD;
         11. Significant deviation from normal in either: history, physical examination or&#xD;
             laboratory tests as evaluated by the Principle Investigator. Participants with a&#xD;
             history of uncontrolled hypertension, uncontrolled diabetes, hypercalciuria,&#xD;
             nephrolithiasis and active sarcoidosis or tuberculosis will also be excluded.&#xD;
&#xD;
         12. Participation in another investigational trial 30 days prior to screening.&#xD;
&#xD;
         13. Spinal disease that affects interpretation of bone densitometry like scoliosis with a&#xD;
             Cobb angle greater than 15o, history of surgery at lumbosacral spine.&#xD;
&#xD;
         14. Bilateral hip replacement.&#xD;
&#xD;
         15. Currently smoking more than 10 cigarettes daily.&#xD;
&#xD;
         16. Currently consuming more than 2 units of alcohol daily. (One unit is equivalent to a&#xD;
             standard glass of beer (285ml), a single measure of spirits (30ml), a medium-sized&#xD;
             glass of wine (120ml), or 1 measure of an aperitif (60ml)&#xD;
&#xD;
         17. Unable to perform DXA due to excessive body girth/width. Body width on DXA &gt; 25 cm.&#xD;
&#xD;
         18. Patients who are deemed unsafe to perform muscular function testing as evaluated by&#xD;
             the investigator.&#xD;
&#xD;
         19. Class III obesity.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Aloia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Winthrop University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mageda Mikhail, MD</last_name>
    <role>Study Director</role>
    <affiliation>Winthrop University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Winthrop University Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 10, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>October 20, 2021</last_update_submitted>
  <last_update_submitted_qc>October 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vitamin D supplementation</keyword>
  <keyword>calcium supplementation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02969850
org study id: 19-00873
nct id: NCT02969850
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Compare free 25(OH)D levels in Caucasian women (current study) and AA women (from prior study)
time frame: baseline
description: VDBP will be measured and free 25(OH)D calculated
measure: Compare Vitamin D metabolite ratio (VMR) in Caucasian women (current study) and AA women (from prior study)
time frame: baseline
description: serum 24,25(OH)2D and serum 25(OH)D will be measured and VMR calculated
measure: Relationship between free 25(OH)D and two measures of bone health (PTH and BMD)
time frame: baseline
description: Relationships will be assessed via correlation and regression analyses
measure: Relationship between VMR and two measures of bone health (PTH and BMD)
time frame: baseline
description: Relationships will be assessed via correlation and regression analyses
measure: Relationship between vitamin D intake and Change in Physical Performance Assessment (SPPB)
time frame: baseline and 6 months
description: Relationships will be assessed via Mixed-Effects Model for Repeated Measures (MMRM)
arm group label: Vitamin D Supplementation
arm group type: Experimental
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Dietary Supplement
intervention name: Vitamin D Supplementation
description: 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.
arm group label: Vitamin D Supplementation
intervention type: Other
intervention name: Placebo
description: Subjects in this group will receive a placebo.
arm group label: Placebo
intervention type: Dietary Supplement
intervention name: Calcium
description: 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.
arm group label: Placebo
arm group label: Vitamin D Supplementation
criteria: 
gender: Female
minimum age: 60 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John Aloia, MD
role: Principal Investigator
affiliation: Winthrop University Hospital
last name: Mageda Mikhail, MD
role: Study Director
affiliation: Winthrop University Hospital
facility: 
country: United States
responsible party type: Sponsor
mesh term: Vitamin D
mesh term: Calcium
sharing ipd: No