Vitamin D Metabolism in Patients With Endocrine Disorders

Study Overview
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Brief Summary
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This prospective controlled interventional study aims to reveal the diversity of vitamin D metabolism in patients with certain endocrine disorders (Cushing's disease, acromegaly, primary hyperparathyroidism, diabetes mellitus type 1) compared to healthy adults. All patients will receive a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3 and D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters will be performed before the intake and on Days 1, 3 and 7 after the administration.

Official Title
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Prospective Non-randomised Controlled Study of Vitamin D Metabolism in Patients With Endocrine Disorders (Acromegaly, Cushing's Disease, Primary Hyperparathyroidism, Diabetes Mellitus Type 1) Treated With Cholecalciferol Bolus Dose

Conditions
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Pituitary ACTH Hypersecretion, Acromegaly, Diabetes Mellitus, Type 1, Primary Hyperparathyroidism

Intervention / Treatment
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* Drug: Cholecalciferol 15000 UNT/ML Oral Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed diagnosis (arms Cushing's Disease, Acromegaly, Diabetes Mellitus Type 1, Primary Hyperparathyroidism) active phase of the disease (arms Cushing's Disease, Acromegaly) no history of surgical and specific pharmacological treatment (arm Primary Hyperparathyroidism) HbA1c <8.0% (arm Diabetes Mellitus Type 1) absence of the specified endocrine disorders (arm Control group) Exclusion Criteria: factors associated with vitamin D level intake of the following drugs during the 3 months preceding the study: vitamin D medications; glucocorticosteroids; antiretroviral drugs; antifungal drugs; cholestyramine, orlistat; antiepileptic drugs; antidepressants (fluoxetine); diuretics (spironolactone); antimicrobial agents (macrolides, tetracyclines, isoniazid, rifampin, primaquine); chemotherapy (cyclophosphamide, tamoxifen, paclitaxel, ifosfamide, irinotecan, etoposide, vinblastine); immunosuppressants (cyclosporin A, tacrolimus, sirolimus); H2 receptor antagonists. BMI >35 kg/m2 pregnancy granulomatous disease (sarcoidosis, tuberculosis, histoplasmosis, berylliosis, coccidiomycosis) disease with malabsorption syndrome (Crohn's disease, ulcerative colitis, celiac disease, post-bariatric surgery condition, decompensation of chronic pancreatitis) reduced renal function (eGFR <60 ml/min/1.73m2) laboratory signs of liver failure (hypoalbuminemia, hypoprothrombinemia) hypercalcemia or risk factors for hypercalcemia serum total calcium >3.0 mmol/L myeloma immobilization thiazide diuretics intake allergy to vitamin D drugs total 25(ОН)D >60 ng/ml (determined by chemiluminescent immunoanalysis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cushing's Disease<br> | Drug: Cholecalciferol 15000 UNT/ML Oral Solution<br>* A single dose (150,000 IU) of cholecalciferol aqueous solution per os<br>|
| Experimental: Acromegaly<br> | Drug: Cholecalciferol 15000 UNT/ML Oral Solution<br>* A single dose (150,000 IU) of cholecalciferol aqueous solution per os<br>|
| Experimental: Diabetes Mellitus Type 1<br> | Drug: Cholecalciferol 15000 UNT/ML Oral Solution<br>* A single dose (150,000 IU) of cholecalciferol aqueous solution per os<br>|
| Experimental: Primary Hyperparathyroidism<br> | Drug: Cholecalciferol 15000 UNT/ML Oral Solution<br>* A single dose (150,000 IU) of cholecalciferol aqueous solution per os<br>|
| Experimental: Control group<br> | Drug: Cholecalciferol 15000 UNT/ML Oral Solution<br>* A single dose (150,000 IU) of cholecalciferol aqueous solution per os<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline 25(OH)D3 level | Measured in ng\mL. | Day 0 | 
| Change in 25(OH)D3 level | Measured in ng\mL. | Day 1, 3, 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum total calcium | Measured in mmol\L | Day 0, 1, 3, 7 | 
| Serum albumin-adjusted calcium | Measured in mmol\L | Day 0, 1, 3, 7 | 
| Serum phosphorus | Measured in mmol\L | Day 0, 1, 3, 7 | 
| Serum PTH | Measured in pg/mL | Day 0, 1, 3, 7 | 
| Serum creatinine | Measured in μmol/L | Day 0, 1, 3, 7 | 
| Serum albumin | Measured in g/L | Day 0, 1, 3, 7 | 
| Serum magnesium | Measured in mmol\L | Day 0, 1, 3, 7 | 
| Calcium-creatinine ratio in spot urine | Measured in mmol/mmol | Day 0, 1, 3, 7 | 
| Phosphorus-creatinine ratio in spot urine | Measured in mmol/mmol | Day 0, 1, 3, 7 | 
| 1,25(OH)2D3 level | Measured in pg\mL. | Day 0, 1, 3, 7 | 
| 24,25(OH)2D3 level | Measured in ng\mL. | Day 0, 1, 3, 7 | 
| 3-epi-25(OH)D3 level | Measured in ng\mL. | Day 0, 1, 3, 7 | 
| 25(OH)D2 level | Measured in ng\mL. | Day 0, 1, 3, 7 | 
| D3 level | Measured in ng\mL. | Day 0, 1, 3, 7 | 
| 25(OH)D3/24,25(OH)2D3 ratio |  | Day 0, 1, 3, 7 | 
| 25(OH)D3/1,25(OH)2D3 ratio |  | Day 0, 1, 3, 7 | 
| Serum free 25(OH)D | Measured in pg/mL | Day 0, 1, 3, 7 | 
| Serum vitamin D-binding protein | Measured in mg/L | Day 0, 1, 3, 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholecalciferol, Vitamin D, Vitamin D deficiency, Chromatography, Liquid, Tandem Mass Spectrometry