To Study the Nutri-Genomic Response of Vit-D Supplementation in African-Americans
Condition: Hypovitaminosis D
MeSH terms: Rickets; Avitaminosis; Vitamin D Deficiency
Study type: Interventional

Summary: 
      Three hundred thirty (330) overweight, pre-hypertensive/controlled hypertensive,
      African-American participants will be enrolled in a 8 week study to assess the effect of two
      administrations of Vitamin D3 on Vitamin D serum responsiveness as a function of clinical,
      biologic and genetic factors. The investigators anticipate that at least 300 participants
      will complete this study.

      Written, signed and dated informed consent to participate in the study will be given by the
      participant or a legally acceptable representative, in accordance with the International
      Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable
      regulations, before completing any study-related activities/procedures. The original signed
      and dated consent will be kept in the subject's research file and a copy given to the
      subject. A copy will also be placed in their medical record.
    

Detailed description: 
      DETAILED DESCRIPTION OF STUDY PROCEDURES. Three hundred thirty (330) overweight,
      pre-hypertensive/controlled hypertensive, African-American participants will be enrolled in a
      8 week study to assess the effect of two administrations of Vitamin D3 on Vitamin D serum
      responsiveness as a function of clinical, biologic and genetic factors. The investigators
      anticipate that at least 300 participants will complete this study.

      Written, signed and dated informed consent to participate in the study will be given by the
      participant or a legally acceptable representative, in accordance with the International
      Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable
      regulations, before completing any study-related activities/procedures. The original signed
      and dated consent will be kept in the subject's research file and a copy given to the
      subject. A copy will also be placed in their medical record.

      BLOOD PRESSURE CONTROL. Controlled high blood pressure is entry criteria, but not an outcome.
      However, the investigators want to exclude potential participants who are likely to have poor
      BP control during the study. Therefore, although patients with pre-hypertension or
      hypertension are eligible to be entered into the study, the protocol only allows enrollment
      of participants with well-controlled hypertension as defined by SBP≥ 120 mmHg or DBP ≥ 80
      mmHg if not on treatment, and SBP <160 mmHg or DBP < 100 mmHg regardless of whether on
      treatment or not. BP care will be managed by the participants' primary or other provider. All
      participants being actively treated for hypertension with pharmacotherapy will receive
      direction to adhere to their medication and to follow-up with their Primary Care Physician.
      Patients with poorly controlled diabetes as defined by hemoglobin A1c > 8.5% or advanced
      kidney disease as defined by eGFR < 45 ml/min are excluded. After the study is concluded, all
      participants will be encouraged and supported to address issues of diet and exercise that may
      reduce their risk for hypertension. If BP medications need to be adjusted, participants will
      be referred back to their Primary Care Physician.

      VISIT 1 - SCREENING. The screening period will allow for the determination of appropriateness
      of each subject's inclusion in the study. Written informed consent from the subject or their
      legally authorized representative would have been obtained prior to any study-related
      procedures being performed. In addition to signing the general informed consent, subjects who
      agree to participate the sub-study with fat biopsy will sign a second informed consent.

      The subject will be assigned a screening number and will be contacted regarding eligibility
      once all screening procedures have been performed and laboratory results received.

      The following evaluations and assessments will be performed during Screening:

      inclusion/exclusion criteria, medical history (including demographics and concomitant
      medications, including prescription, herbal/vitamins, and all over-the-counter medications),
      vital signs (sitting BP, heart rate), and a mini physical examination (which will include
      height (cm), weight (kg), and waist circumference (cm) from which body mass index (BMI) will
      be calculated and a clinical heart/lung examination. Blood will be drawn (15 cc) for full
      biochemistry panel with glucose (mg/dl), complete blood count, HbA1c (%), calcium (mg/dl),
      phosphorus (mg/dl), albumin (mg/dl), pregnancy test and 25(OH)D (ng/ml) levels. After
      screening information is reviewed and deemed to be appropriate for inclusion in the study,
      eligible subjects will be given an appointment and preparatory instructions for Visit 2
      (Baseline/Randomization/Dose#1). Instructions include cessation of smoking (if they smoke),
      eating, or drinking caffeine for at least 8 hours prior to the Baseline Visit. If
      participants are taking prescribed medications, they will be asked to bring them and advised
      to take them as prescribed.

      VISIT 2 - BASELINE/ RANDOMIZATION/ STUDY DRUG DOSE#1 ADMINISTRATION. If subject meets all of
      the inclusion/exclusion criteria, they will be randomized. The participant will be asked
      about any adverse events and changes in medications, including prescription, herbal/vitamin,
      and over-the-counter medications. Vital signs (sitting BP, heart rate) will be obtained and a
      nutritional survey administered. Blood will be drawn (45 cc) for serum calcium (mg/dl),
      phosphorus (mg/dl), albumin (mg/dl), iPTH (pg/ml) and 1-84 PTH/7-84 PTH ratio, pregnancy
      test, 25(OH)D (ng/ml) levels; and samples stored for bio-markers (e.g.
      pro-inflammatory/pro-thrombotic/fibrotic, insulin sensitivity, and vitamin D receptor
      polymorphisms). Spot urine sample (30cc) will be collected for calcium/creatinine and
      albumin/creatinine ratios as well as sodium and isoprostanes. The fat biopsy will be
      performed on those that agree to be part of the subgroup. Participants undergoing the fat
      biopsy will be given post biopsy instructions including a return appointment in 7-10 days.

      Visit will last about 30-60 minutes for most participants. At the end of the visit,
      participant will be randomized and given either two 50,000 IU tablets of oral Vitamin D3
      [also known as cholecalciferol or 25 hydroxy-Vitamin D3 or 25 (OH) D3] or two tablets of
      Placebo (microcrystalline cellulose) to take under direct observation. All the participants
      will be given an appointment and preparatory instructions for Study Visit 3. They will also
      be asked to avoid any other vitamin D supplements during study period.

      VISIT 3 - STUDY DRUG DOSE#2 ADMINISTRATION (2 weeks after baseline). Visit will last about 15
      minutes for most participants. Participant will be asked about any adverse events and changes
      in medications, including prescription, herbal, and over-the-counter medications. Vital signs
      will be obtained. Participant will be given their second dose of either two 50,000 IU tablets
      of oral Vitamin D3 or two tablets of Placebo to take under direct observation. All the
      participants will be given an appointment and preparatory instructions for Study Visit 4
      (Week 6).

      VISIT 4 (Week 6). During this visit participant will be asked about any adverse events
      including possible symptoms of vitamin D overdose and changes in medications, including
      prescription, herbal, and over-the-counter medications. In addition, the following
      evaluations and assessments will also be performed: vital signs (sitting BP, heart rate).
      Blood will be drawn (3 tablespoon or 45 cc) for full biochemistry panel, with glucose
      (mg/dl), HbA1c (%), complete blood count, calcium (mg/dl), phosphorus (mg/dl), albumin
      (mg/dl), iPTH (pg/ml) and 1-84 PTH/7-84 PTH ratio, and 25(OH)D (ng/ml) levels; and stored
      samples for bio markers (e.g. pro-inflammatory/pro- thrombotic/fibrotic, insulin sensitivity,
      and vitamin D receptor polymorphisms). Spot urine sample will be collected for
      calcium/creatinine and albumin/creatinine ratios as well as sodium and isoprostanes. Urine
      pregnancy test will also be done. Participants undergoing the fat biopsy will be given post
      biopsy instructions and will have an additional 7-10 days of follow-up.

      VISIT 5 - END OF STUDY (Week 8). At the End of Study visit (EOS), participant will be asked
      about any adverse events including possible symptoms of vitamin D overdose. In addition, the
      following evaluations and assessments will also be performed: vital signs (sitting BP and
      heart rate). The results of the labs from the previous visit will be discussed and if there
      are any abnormal lab values, participant will be referred to primary care physician for
      further management.
    

Intervention name(s): 25 Hydroxy- Vitamin D3 [25 (OH) D3]; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Two 50,000 IU tablets of oral Vitamin D3 [also known as cholecalciferol or 25 hydroxy-Vitamin D3 or 25 (OH) D3] will be given at baseline and 2 weeks after the baseline visit under direct observation by the nurse or research coordinator.
Other intervention name(s): Vitamin D3
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Calcifediol; Hydroxycholecalciferols; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Vitamin D; Hypovitaminosis D; HTN