Vitamin D Homeostasis in Sarcoidosis

This study evaluates the relationship between vitamin-D status and severity of sarcoidosis, and the effects of vitamin-D repletion in vitamin-D insufficient patients with sarcoidosis. Half the patients with sarcoidosis who are vitamin-D insufficient will receive standard vitamin-D supplementation via standard regimen while the other half will receive a placebo. Sarcoidosis patients who are vitamin-D sufficient will also act as controls.

Sarcoidosis is a multi-system inflammatory disease characterized by T-helper lymphocyte hyperactivity leading to granulomatous inflammation. The granuloma cells autonomously convert 25-hydroxy-vitamin-D (25OHD) to the active metabolite 1,25-dihydroxy-vitamin-D (1,25OH2D) independent of normal feedback control but dependent on substrate (25OHD) concentration. Circulating 1,25OH2D exerts both anti-inflammatory and mineral metabolic actions. Deficiency of 25OHD limits substrate-dependent 1,25OH2D synthesis, diminishes anti-antigenic innate immunity and augments pro-inflammatory adaptive immunity. Thus, low vitamin-D stores could aggravate sarcoid inflammation while repletion of vitamin-D stores could mitigate inflammation in sarcoidosis.

Vitamin-D insufficient subjects will receive either vitamin D2 repletion or placebo Vitamin-D sufficient subjects will be observed without treatment.

Groups separated by a) use / non-use of oral prednisone, and b) status of serum 25-hydroxy-vitamin-D level (sufficient or insufficient). Those who are vitamin-D insufficient will be randomized to receive either vitamin D2 or placebo.

Low serum vitamin D level, split by use or non-use of systemic corticosteroid. Vitamin D2 (Ergocalciferol) 50,000 units will be given by mouth once a week for 12 weeks, then once a month for 12 weeks. Daily dietary requirement (calcium citrate with vitamin D2 (200 mg/250 Units tablets, 4 tablets per day) will be given by mouth for 24 weeks).

Low serum vitamin D level, split by use or non-use of systemic corticosteroid. Placebo capsules of identical size and appearance will be given by mouth once a week for 12 weeks, then once a month for 12 weeks. Daily dietary requirement (calcium citrate with vitamin D2 (200 mg/250 Units tablets, 4 tablets per day) will be given by mouth for 24 weeks).

Normal serum vitamin D level, split by use or non-use of systemic corticosteroid. Daily dietary requirement (calcium citrate with vitamin D2 (200 mg/250 Units tablets, 4 tablets per day) will be given by mouth for 24 weeks).

Standard validated questionnaire for assessing the impact of sarcoidosis on quality of life. Questions address symptoms, activities and psychosocial impacts of disease. It consists of 29 questions on general health, medications, and symptoms in lung, skin, and eyes, summed to derive a total score. Each question is scored on a scale of 1 (worst) to 7 (best). Minimum total score = 5 (poorest health). Maximum total score = 203 (best health).

Inclusion Criteria: Stable medical condition defined as no hospitalization or emergency room visit in the previous 3 months No evidence of active pulmonary or systemic infection No other active inflammatory disease, No active malignancy. Normal serum ionized calcium level Exclusion Criteria: Hospitalization or emergency room visit in the previous 3 months Evidence of active pulmonary or systemic infection Evidence of active other inflammatory disease Evidence of active malignancy Elevated serum ionized calcium level

Data access requests will be reviewed by an external independent review panel. Requestors will be required to sign a Data Access Agreement.

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