Vitamin D Homeostasis in Sarcoidosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Vitamin D Homeostasis in Sarcoidosis

Conditions
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Sarcoidosis, Vitamin D Insufficiency

Intervention / Treatment
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* Drug: Ergocalciferol
* Drug: Placebo
* Drug: Calcium Citrate with Vitamin D2


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Vitamin-D insufficient subjects will receive either vitamin D2 repletion or placebo Vitamin-D sufficient subjects will be observed without treatment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low vit-D, Ergocalciferol<br>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). | Drug: Ergocalciferol<br>* Vitamin D2 50,000 units<br>* Other names: Vitamin D2;Drug: Calcium Citrate with Vitamin D2<br>* To meet the recommended minimum daily dietary requirements<br>* Other names: Citracal;|
| Placebo Comparator: Low vit-D, Placebo<br>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). | Drug: Placebo<br>* Sugar pill manufactured to mimic ergocalciferol 50,000 units<br>* Other names: Placebo oral tablets;Drug: Calcium Citrate with Vitamin D2<br>* To meet the recommended minimum daily dietary requirements<br>* Other names: Citracal;|
| Other: Normal vit-D, control<br>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). | Drug: Calcium Citrate with Vitamin D2<br>* To meet the recommended minimum daily dietary requirements<br>* Other names: Citracal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lung function from baseline | (Measurement at end of study)/(measurement at enrollment) | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in King's Sarcoidosis Questionnaire Score | 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). | Baseline, 12 and 24 weeks | 
| Change in six minute walk distance | (Measurement at end of study)/(measurement at enrollment) | Baseline and 24 weeks | 
| Change in blood cell counts from complete blood count (CBC) | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in metabolic profile from complete metabolic panel (CMP) | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in serum vitamin-D metabolite concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in serum angiotensin converting enzyme (ACE) concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in serum serum gamma-globulin concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in serum C-reactive protein (CRP) concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in serum tumor Necrosis factor-alpha (TNF-alpha) concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in serum interferon-gamma (IFN-gamma) concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Changes in serum interleukin concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in 24 hour urine calcium/creatinine ratio | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in 24 hour urine deoxypyridinoline concentration | (Measurement at study point)/(initial measurement at enrollment) | Baseline, 12 and 24 weeks | 
| Change in fractional lung tissue volume on computed/positron emission tomography (PET/CT) | (Measurement at end of study)/(measurement at enrollment) | Baseline and 24 weeks | 
| Change in Fluoro-deoxyglucose (FDG) uptake on PET/CT | (Measurement at end of study)/(measurement at enrollment | Baseline and 24 weeks | 
| Change in bone density z-score | (Measurement at end of study)/(measurement at enrollment) | Baseline and 24 weeks |