To Study the Nutri-Genomic Response of Vit-D Supplementation in African-Americans
To Study the Nutri-Genomic Response of Vit-D Supplementation in African-Americans
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 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.
Inclusion Criteria:

 -  Males or females, 18-70 years of age and self-identified as African-American or Black

 -  Pre-hypertension or hypertension (well controlled - see below)

 -  If a potential study patient is not on treatment their SBP must be > 120 mmHg, or DBP
 > 80 mmHg

 -  Whether on treatment or not SBP must be <160 mmHg and DBP must be < 100 mmHg (BP is
 not an outcome. Controlled BP is for participant safety)

 -  Screening Vitamin D (D2 and D3 level) >5 and < 25 ng/ml (recommended normal level is >
 30 ng/ml)

 -  Body mass index (BMI) > 25 kg/m2 and < 45 kg/m2

 -  Any female of non-childbearing potential, including any female who:

 -  has had a hysterectomy,

 -  has had a bilateral oophorectomy,

 -  has had a bilateral tubal ligation or

 -  is postmenopausal (demonstration of total cessation of menses for ≥ 1 year prior
 to the date of the screening visit)

 -  Any female of child-bearing potential must agree to use at least one form of
 contraception (may be a barrier method), during the full duration of the study.

 Exclusion Criteria:

 -  Concurrent Disease:

 -  Poorly controlled high blood pressure (SBP ≥160 mmHg or DBP ≥ 100 mmHg)

 -  Poorly controlled diabetes (HbA1c >8.5%)

 -  Screening Vitamin D (D2 and D3 level) < 5 or > 25 ng/ml (recommended normal level
 is > 30 ng/ml)

 -  Estimated glomerular filtration rate (eGFR) < 45 ml/min

 -  Evidence of disease that could result in hypercalcemia

 -  History of kidney stones (less than one year prior to screening)

 -  History of drug, alcohol, or illicit substance abuse (within the past 6 months)

 -  History of another chronic disease which the investigator feels should preclude
 the subject from entering the study (e.g. cancer, immunologic disorder)

 -  Liver function tests (LFTs) greater than twice the upper limit of normal

 -  Subjects requiring chronic use of nonsteroidal anti-inflammatory drugs or aspirin
 >325 mg/day

 -  Subjects requiring treatment with other vitamin D preparations containing more
 than 400 IU of vitamin D

 -  Subjects requiring chronic use of immunosuppressive therapy or corticosteroids

 -  Recent (<6 months) myocardial infarction, stroke, or hospitalization for
 congestive heart failure

 -  Subjects with clinically apparent hypothyroidism or thyrotoxicosis

 -  Allergy/intolerance: known allergy to oral vitamin D or microcrystalline
 cellulose

 -  Any female of child-bearing potential who declines to use some method of birth
 control during the study period

 Other:

 -  Concurrent participation in other clinical trials or taking experimental medications
 or within 30 days of completing another trial or study.

 -  Patients who are unable to give informed consent

 -  Patients who, in the opinion of the Investigator, have a condition which would
 interfere with their evaluation (e.g. severe mental health disorder)

 -  Patients who, in the opinion of the Investigator, may experience an unacceptable
 health risk by participating in this study

 -  Patients who are pregnant or lactating

 -  Not African- American or Black by self-identification

 -  Body mass index (BMI) > 45 kg/m2