Vitamin D Metabolism in Patients With Endocrine Disorders

Sponsor

Endocrinology Research Centre, Moscow (Other)

Overall Status

Completed

CT.gov ID

NCT04844164

Collaborator

Russian Science Foundation (Other)

261

Enrollment

Location

Arms

25.5

Actual Duration (Months)

10.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pituitary ACTH Hypersecretion Acromegaly Diabetes Mellitus, Type 1 Primary Hyperparathyroidism	Drug: Cholecalciferol 15000 UNT/ML Oral Solution	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

261 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Apr 16, 2019

Actual Primary Completion Date :

May 15, 2021

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)