Clinical trial NCT03621553: Vitamin D Homeostasis in Sarcoidosis
Official title: Vitamin D Homeostasis in Sarcoidosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Sarcoidosis
Vitamin D Insufficiency
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2018-08-08
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Vitamin-D insufficient subjects will receive either vitamin D2 repletion or placebo Vitamin-D sufficient subjects will be observed without treatment.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in lung function from baseline
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Change in King's Sarcoidosis Questionnaire Score
timeFrame: Baseline, 12 and 24 weeks
measure: Change in six minute walk distance
timeFrame: Baseline and 24 weeks
measure: Change in blood cell counts from complete blood count (CBC)
timeFrame: Baseline, 12 and 24 weeks
measure: Change in metabolic profile from complete metabolic panel (CMP)
timeFrame: Baseline, 12 and 24 weeks
measure: Change in serum vitamin-D metabolite concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in serum angiotensin converting enzyme (ACE) concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in serum serum gamma-globulin concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in serum C-reactive protein (CRP) concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in serum tumor Necrosis factor-alpha (TNF-alpha) concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in serum interferon-gamma (IFN-gamma) concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Changes in serum interleukin concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in 24 hour urine calcium/creatinine ratio
timeFrame: Baseline, 12 and 24 weeks
measure: Change in 24 hour urine deoxypyridinoline concentration
timeFrame: Baseline, 12 and 24 weeks
measure: Change in fractional lung tissue volume on computed/positron emission tomography (PET/CT)
timeFrame: Baseline and 24 weeks
measure: Change in Fluoro-deoxyglucose (FDG) uptake on PET/CT
timeFrame: Baseline and 24 weeks
measure: Change in bone density z-score
timeFrame: Baseline and 24 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center, and Parkland Health and Hospital System
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Connie Hsia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.