Please select the eligibility criteria that correspond to the clinical trial below.
Title: Can Vitamin D Supplementation Prevent Bone Loss in Persons With MS? A Randomised, Placebo-controlled, Single-centre Study
Brief Summary: Several studies have shown that bone mineral density (BMD) at the femoral neck decreases with increasing physical handicap (EDSS-score) in MS patients. Possible explanations are less weightbearing exercise or less UV-exposure resulting in reduced vitamin D generation in the skin. Prevention of osteoporosis is a high priority, because treatment of the established disease remains sub-optimal.

We have designed a double-blind randomised controlled trial of two years' duration including 90-100 persons with MS age 18-50 to assess whether supplementation with vitamin D, given as a weekly dose of 20,000 IU cholecalciferol, can prevent bone loss.

The primary objective of this study is to determine changes in BMD over the 2 year study period comparing treatment and placebo groups.

The most important secondary objective is to determine cytokine profiles in blood samples. We will also assess parameters related to vitamin D status and physical performance.


Options:
A: Inclusion Criteria:

* age 18 to 55 years
* remitting-relapsing multiple sclerosis according to McDonald criteria who fulfill the reimbursement criteria for interferon-beta and have used interferon-beta-1b for at least one month
* EDSS (expanded disability statsu scale) ≤ 5
* no neutralising antibodies to INFB as measured by indirect MxA test
* prepared and considered to follow the protocol
* using appropriate contraceptive methods (women of childbearing potential)
* has given informed consent

Exclusion Criteria:

* serum calcium \>2.6 mmol/L
* serum 25(OH)D2 (kalsidiol) \> 85 nmol/L
* presence of primary hyperparathyroidism (serum intact PTH, parathyroid hormone)\>65 ng/L)
* pregnancy or unwillingness to use contraception
* alcohol or drug abuse
* use of glucocorticoid treatment other than intravenous methylprednisolone for treatment of relapses
* current use of other immunomodulatory therapy than interferon-beta-1b
* known allergy to cholecalciferol or arachis oil (peanuts)
* therapy with digitalis, calcitonin or active vitamin D3 analogues during the previous 12 months or multivitamins containing vitamin D during previous two weeks preceding study entry
* any condition predisposing to hypercalcaemia (such as any type of cancer)
* sarcoidosis
* nephrolithiasis or renal insufficiency, serum creatinine above 1.5 times the normal upper reference limit
* significant hypertension (Blood Pressure \<180/110 mmHg)
* hyperthyroidism, or hypothyroidism in the year before the study began
* a history of nephrolithiasis during the previous five years
* cardiac insufficiency or significant cardiac dysrhythmia
* unstable or advanced ischaemic heart disease
* has suffered a major depression
B: Inclusion Criteria:

* Male and female patients with a diagnosis of RRMS according to the McDonald criteria (2005)
* At least 18 years of age
* Patients are treated with IFN-beta for RRMS. The decision to treat with IFN beta will be independent from this study protocol.
* Patients will be either newly diagnosed, who are going to start IFN beta therapy for the first time or RRMS patients who suffer from FLS while being treated with IFN beta.
* Insufficient blood levels of 25-hydroxy-vitamin D (below 75nmol/l according to current definitions.
* EDSS score up to 7
* Willing and able to give informed consent

Exclusion Criteria:

* Patients having abnormalities of vitamin D related hormonal system other than low dietary intake or decreased sun exposure will be excluded. Namely, malabsorption \[Celiac, Whipple, Inflammatory bowl disease, Intestinal bypass surgery, Short bowel syndrome, Cirrhosis, Nephrotic syndrome, Hyperthyroidism, Renal failure \[creatinine clearance of less than 40 ml/min\], Rickets, Hypoparathyroidism, Hypercalcemia at baseline, known malignancy, granulomatous disorders (Sarcoidosis, Tuberculosis, Silicosis) and Lymphomas.
* Patients who take medications that influence vitamin D metabolism, other than corticosteroids, will be also excluded. Namely, Orlistat, Anticonvulsants \[Phenobarbital, Primidone, Phenytoin\], Rifampin, Isoniazide, ketoconazole, 5FU and Leucovorin
* Patients with conditions with increased susceptibility to hypercalcemia will be excluded too: known arrhythmia or heart disease, treatment with Digitalis, or Hydrochlorothiazide.and those who suffer from nephrolithiasis.
* Other Central Nervous System disorders than RRMS
* Psychiatric disorders such as psychosis, bipolar disorder or substance abuse
* Pregnancy
* Contra-indication to treatment with IFN-beta
C: Inclusion Criteria:

* Age 18 to 50 years
* EDSS \< 4.0 (able to walk without rest some 500 m)
* Women have to be premenopausal
* MS according to the McDonald criteria; prepared and considered able to follow the protocol; using appropriate contraceptive methods (women of childbearing potential)
* Having given written informed consent.

Exclusion Criteria:

* Pregnancy or unwillingness to use contraception; alcohol or drug abuse
* Use of glucocorticoid treatment other than intravenous methylprednisolone for treatment of relapses
* Known allergy to cholecalciferol or arachis oil (peanuts)
* Therapy with digitalis, calcitonin, active vitamin D3 analogues, fluoride, or bisphosphonates during the previous 12 months
* Any condition predisposing to hypercalcaemia
* Nephrolithiasis or renal insufficiency
* Presence of primary hyperparathyroidism, hyperthyroidism, or hypothyroidism in the year before the study began; a history of nephrolithiasis during the previous five years.
D: Inclusion Criteria:

* Clinically definite MS
* Age 18-55
* EDSS 0-6.5

Exclusion Criteria:

* EDSS =\> 7.0
* Current Vitamin D3 use \>4000 IU/d
* Baseline (25(OH)D) level \<20 mmol/L (frank deficiency) and \>150 mmol/L
* Pregnancy or inability/unwillingness to use contraception
* History of cardiac arrhythmia
* History of renal disease and nephrolithiasis
* History of granulomatous disease or lymphoma
* Relapse activity or steroid use in the past 60 days

Answer: C