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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sarcoidosis; Vitamin D Insufficiency
• Intervention / Treatment: Drug: Ergocalciferol; Drug: Calcium Citrate with Vitamin D2; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-9034
      • University of Texas Southwestern Medical Center, and Parkland Health and Hospital System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Connie Hsia, MD, University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• Capolongo G, Xu LH, Accardo M, Sanduzzi A, Stanziola AA, Colao A, Agostini C, Zacchia M, Capasso G, Adams-Huet B, Moe OW, Maalouf NM, Sakhaee K, Hsia CC. Vitamin-D status and mineral metabolism in two ethnic populations with sarcoidosis. J Investig Med. 2016 Jun;64(5):1025-34. doi: 10.1136/jim-2016-000101. Epub 2016 Apr 6.
• Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):575-9. doi: 10.1016/j.jsbmb.2004.03.038.
• Bolland MJ, Wilsher ML, Grey A, Horne AM, Fenwick S, Gamble GD, Reid IR. Randomised controlled trial of vitamin D supplementation in sarcoidosis. BMJ Open. 2013 Oct 23;3(10):e003562. doi: 10.1136/bmjopen-2013-003562.
• Kamphuis LS, Bonte-Mineur F, van Laar JA, van Hagen PM, van Daele PL. Calcium and vitamin D in sarcoidosis: is supplementation safe? J Bone Miner Res. 2014 Nov;29(11):2498-503. doi: 10.1002/jbmr.2262.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hypersensitivity; Hypersensitivity, Delayed; Sarcoidosis; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: STU 062010-055

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data for primary and secondary outcome measures will be made available.
• IPD Sharing Time Frame: Within 6 months of study completion
• IPD Sharing Access Criteria: Data access requests will be reviewed by an external independent review panel. Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes