Sarcoidosis, Vitamin D Insufficiency
Conditions
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.
Interventions
DRUGErgocalciferol
Vitamin D2 50,000 units
DRUGPlacebo
Sugar pill manufactured to mimic ergocalciferol 50,000 units
DRUGCalcium Citrate with Vitamin D2
To meet the recommended minimum daily dietary requirements
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
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.
Intervention model description
Vitamin-D insufficient subjects will receive either vitamin D2 repletion or placebo Vitamin-D sufficient subjects will be observed without treatment.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in lung function from baseline | Baseline and 24 weeks | (Measurement at end of study)/(measurement at enrollment) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 six minute walk distance | Baseline and 24 weeks | (Measurement at end of study)/(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 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 serum C-reactive protein (CRP) concentration | Baseline, 12 and 24 weeks | (Measurement at study point)/(initial 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) |
| Changes in serum interleukin 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 24 hour urine deoxypyridinoline 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 |
| Change in bone density z-score | Baseline and 24 weeks | (Measurement at end of study)/(measurement at enrollment) |
Countries
United States
Contacts
CONTACTConnie Hsia, MD
CONTACTKhashayar Sakhaee, MD
PRINCIPAL_INVESTIGATORConnie Hsia, MD
University of Texas Southwestern Medical Center
Outcome results
None listed