Vitamin D Metabolism in Patients With Endocrine Disorders

Phase 1

Completed

• Conditions: Acromegaly; Pituitary ACTH Hypersecretion; Diabetes Mellitus, Type 1; Primary Hyperparathyroidism
• Interventions: Drug: Cholecalciferol 15000 UNT/ML Oral Solution

• Registration Number: NCT04844164
• Lead Sponsor: Endocrinology Research Centre, Moscow

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-16
• Study First Submitted: 2021-04-09
• Study First Submitted QC: 2021-04-09
• Study First Posted: 2021-04-14
• Primary Completion: 2021-05-15
• Study Completion: 2021-06-01
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-10
• Last Update Posted: 2022-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 261

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Primary Hyperparathyroidism	Cholecalciferol 15000 UNT/ML Oral Solution	-
Control group	Cholecalciferol 15000 UNT/ML Oral Solution	-
Cushing's Disease	Cholecalciferol 15000 UNT/ML Oral Solution	-
Acromegaly	Cholecalciferol 15000 UNT/ML Oral Solution	-
Diabetes Mellitus Type 1	Cholecalciferol 15000 UNT/ML Oral Solution	-

Primary Outcome Measures

Name	Time	Method
Baseline 25(OH)D3 level	Day 0	Measured in ng\\mL.
Change in 25(OH)D3 level	Day 1, 3, 7	Measured in ng\\mL.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Endocrinology Research Centre, Moscow; 🇷🇺 Moscow, Russian Federation