Vitamin D Metabolism in Patients With Endocrine Disorders

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Endocrinology Research Centre, Moscow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control group	Drug: Cholecalciferol 15000 UNT/ML Oral Solution; A single dose (150,000 IU) of cholecalciferol aqueous solution per os
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Endocrinology Research Centre, Moscow
• Collaborators: Russian Science Foundation
• Investigators: Principal Investigator: Liudmila Rozhinskaya, MD, PhD, Endocrinology Research Centre, Moscow

Publications and helpful links

General Publications

• Povaliaeva A, Pigarova E, Zhukov A, Bogdanov V, Dzeranova L, Mel'nikova O, Pekareva E, Malysheva N, Ioutsi V, Nikankina L, Rozhinskaya L. Evaluation of Vitamin D Metabolism in Patients with Type 1 Diabetes Mellitus in the Setting of Cholecalciferol Treatment. Nutrients. 2020 Dec 18;12(12):3873. doi: 10.3390/nu12123873.
• Povaliaeva AA, Bogdanov VP, Zhukov AY, Pigarova EA, Dzeranova LK, Rozhinskaya LY, Mel'nichenko GA, Mokrysheva NG. Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment. Endocrine. 2022 May;76(2):407-418. doi: 10.1007/s12020-022-02994-0. Epub 2022 Feb 9.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Actual): May 15, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D; Vitamin D deficiency; Cholecalciferol; Tandem Mass Spectrometry; Chromatography, Liquid
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Parathyroid Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hyperparathyroidism; Hyperparathyroidism, Primary; Acromegaly; Endocrine System Diseases; Pituitary ACTH Hypersecretion; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: ERC_2021/01; 19-15-00243 (Other Grant/Funding Number: Russian Science Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No