Vitamin D Homeostasis in Sarcoidosis

Phase 4

Recruiting

• Conditions: Sarcoidosis; Vitamin D Insufficiency
• Interventions: Drug: Placebo; Drug: Calcium Citrate with Vitamin D2; Drug: Ergocalciferol

• Registration Number: NCT03621553
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-07-01
• Study First Submitted: 2018-07-17
• Study First Submitted QC: 2018-08-07
• Study First Posted: 2018-08-08
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-28
• Last Update Posted: 2024-12-03
• Primary Completion: 2025-08-31
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low vit-D, Placebo	Placebo	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 vit-D, control	Calcium Citrate with Vitamin D2	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).
Low vit-D, Ergocalciferol	Calcium Citrate with Vitamin D2	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 vit-D, Placebo	Calcium Citrate with Vitamin D2	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).
Low vit-D, Ergocalciferol	Ergocalciferol	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).

Primary Outcome Measures

Name	Time	Method
Change in lung function from baseline	Baseline and 24 weeks	(Measurement at end of study)/(measurement at enrollment)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center, and Parkland Health and Hospital System; 🇺🇸 Dallas, Texas, United States