Please select the eligibility criteria that correspond to the clinical trial below.
Title: Clinical Approaches to Correcting Vitamin D Inadequacy and Maintaining Adequacy
Brief Summary: Vitamin D is available in two forms, vitamin D2 and vitamin D3. It has previously been assumed that these two forms maintain blood vitamin D equally. However, this may not be the case. This study will evaluate whether D2 and D3 produce equal elevation of blood vitamin D. Additionally, it will evaluate whether once per month vitamin D dosing is as effective in maintaining blood vitamin D levels as daily dosing.


Options:
A: Inclusion Criteria:

* Aged over 65 years with normal renal function
* Normal transaminase levels
* Normal calcium blood levels
* Not homebound (not immobilized) nor in socio-healthcare institutions.

Exclusion Criteria:

* Need for medical treatment with calcium or vitamin D
* Hypersensitivity to or contraindication for calcium or vitamin D
* Medical treatment that includes calcium or vitamin D
* Physical disability that impedes their collaboration
* Taking thiazide diuretics
* Oral anticoagulants
* Hormone replacement therapy
* Digitalis drugs
* Anticonvulsants or barbiturates
* Having any of the following diseases:

  * Lithiasis
  * Renal impairment (serum creatinine \>1.4 mg/dl)
  * Hypo or hyperthyroidism
  * Paget's disease
  * Chronic liver disease
  * Tumors
  * Sarcoidosis
  * Impaired intestinal absorption or chronic alcoholism (\>40 g/day).
B: Inclusion Criteria:

* Ethnicity: all ethnic groups
* Gender: men and women
* Age

  1. Lower age limit: 40 years inclusive
  2. Upper age limit: NONE
* BMI

  1. Lower BMI limit: 25 inclusive
  2. Upper BMI limit: 40 inclusive
* Glucose Intolerance / Mild Diabetes defined as

  1. Fasting glucose ≥100 mg/dl OR
  2. 2-hr glucose after OGTT ≥140 mg/dl OR
  3. 5.8 ≤ Hemoglobin A1c ≤ 7

Major Exclusion Criteria:

* Diabetes requiring pharmacotherapy
* Smoking
* Hyperparathyroidism
* Hypercalcemia (Calcium \> 10.5 mg/dl)
* Kidney stone
* Pregnancy
C: Inclusion Criteria:

1. Community dwelling men and women age ≥ 65 years.
2. Able and willing to sign informed consent.
3. Serum 25OHD concentration ≥ 10 and less than 60 ng/ml by HPLC.
4. Willing to avoid use of cod-liver oil and non-study vitamin D supplementation; standard multiple vitamins containing ≤ 400 IU used no more than once daily will be allowed

Exclusion Criteria:

1. Current hypercalcemia (serum calcium \> 10.5 mg/dl) or untreated primary hyperparathyroidism.
2. History of nephrolithiasis.
3. Screening 25OHD concentration ≥ 60 ng/ml.
4. Baseline 24-hour urine calcium \> 250 mg if female, \> 300 mg if male.
5. Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis, Paget's disease
6. History of any form of cancer within the past five years with the exception of adequately treated squamous cell or basal cell skin cancer.
7. Renal failure defined as a calculated creatinine clearance (Cockroft-Gault method) ≤ 25 ml/minute
8. Severe end-organ disease, e.g., cardiovascular, hepatic, hematologic, pulmonary, etc., which may limit ability to complete the study
9. Known malabsorption syndromes, e.g., celiac disease, radiation enteritis, active inflammatory bowel disease, etc.
10. Use of medications known to alter bone turnover including bisphosphonates, estrogen, selective estrogen receptor modulators, PTH, testosterone or calcitonin
11. Vitamin D intake greater than 5,000 IU daily
12. Treatment with any active metabolites of vitamin D within six months of screening
13. Treatment with any drug which may interfere with vitamin D metabolism, e.g., phenobarbital, phenytoin.
D: Inclusion Criteria:

* Men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose greater than or equal to 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose (FPG) greater than or equal to 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes
* Hemoglobin A1c (A1C) 6.5-9.5% inclusive (for assays with upper limit of normal of 6%) within one month of screening
* Age ≥ 50 years and evidence of vascular disease defined as ≥1of:

  * prior myocardial infarction
  * prior stroke
  * coronary, carotid or peripheral artery revascularization ≥ 4 years earlier
  * previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ECG changes or cardiac enzyme elevation OR
* Age ≥ 55 years and evidence of subclinical vascular disease defined as ≥1 of:

  * microalbuminuria or proteinuria
  * history of treated or untreated hypertension with left ventricular hypertrophy by electrocardiogram (ECG) or echocardiogram

    * 50% stenosis on any imaging of coronary, carotid or lower extremity arteries
  * ankle/brachial index \<0.9 OR
* Age ≥ 60 years and at least 2 of the following cardiovascular disease risk factors:

  * current tobacco use
  * LDL-c ≥3.4 mmol/L (130 mg/dL) or on a lipid lowering medication
  * HDL-c \< 1.0 mmol/L (40 mg/dL) for men and \< 1.3 mmol/L (50 mg/dL) for women or triglycerides ≥ 2.3 mmol/L (200 mg/dL)
  * BP lowering medication use or untreated SBP ≥ 140 mmHg or DBP ≥ 95 mmHg
  * Waist to hip ratio \> 1.0 for men and \> 0.8 for women
* On no insulin and on less than or equal to 2 anti-diabetes drugs where at least one drug is at or below the half-maximal dose (as indicated in the MOP) with stable dosing for 10 weeks prior to screening

Exclusion Criteria:

* Type 1 diabetes
* Current need for insulin treatment
* Symptomatic hyperglycemia requiring immediate therapy in the judgment of the physician
* An acute cardiovascular event within 30 days prior to randomization
* Symptomatic heart failure (i.e. New York Heart Association class II or higher) or any episode of previous pulmonary edema or known ejection fraction \< 0.4 or current use of loop diuretics
* Any fracture within the past 1 year
* Currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery
* Coronary, carotid or peripheral artery revascularization within the 4 years prior to screening in the absence of angina, MI, or stroke in the intervening period
* End stage renal disease requiring renal replacement therapy
* Receiving drug therapy to treat liver disease
* A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer (other than prophylactic)
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \> 2.5 times the upper limit of normal
* A prior heart transplant or awaiting a heart transplant
* Previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication for vitamin D therapy
* Regular use of or indication for greater than 400IU of vitamin D daily
* Clinically or medically unstable with expected survival \< 1 year
* Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data
* Any other factor likely to limit protocol compliance or reporting of adverse events
* Inability to discontinue a TZD (if taking one) in the judgement of the physician/investigator
* Contraindications to or history of hypersensitivity to the investigational products
* History of renal stones within the past 2 years
* Participation in another clinical trial of an investigational agent

Answer: C