Clinical trial NCT04844164: Vitamin D Metabolism in Patients With Endocrine Disorders
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pituitary ACTH Hypersecretion
Acromegaly
Diabetes Mellitus, Type 1
Primary Hyperparathyroidism
Keywords: Vitamin D
Vitamin D deficiency
Chromatography, Liquid
Tandem Mass Spectrometry
Cholecalciferol
Lead sponsor: Endocrinology Research Centre, Moscow
Sponsor class: OTHER_GOV
Collaborators: name: Russian Science Foundation
First posted: 2021-04-14
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Baseline 25(OH)D3 level
timeFrame: Day 0
measure: Change in 25(OH)D3 level
timeFrame: Day 1, 3, 7
Secondary outcomes:
measure: Serum total calcium
timeFrame: Day 0, 1, 3, 7
measure: Serum albumin-adjusted calcium
timeFrame: Day 0, 1, 3, 7
measure: Serum phosphorus
timeFrame: Day 0, 1, 3, 7
measure: Serum PTH
timeFrame: Day 0, 1, 3, 7
measure: Serum creatinine
timeFrame: Day 0, 1, 3, 7
measure: Serum albumin
timeFrame: Day 0, 1, 3, 7
measure: Serum magnesium
timeFrame: Day 0, 1, 3, 7
measure: Calcium-creatinine ratio in spot urine
timeFrame: Day 0, 1, 3, 7
measure: Phosphorus-creatinine ratio in spot urine
timeFrame: Day 0, 1, 3, 7
measure: 1,25(OH)2D3 level
timeFrame: Day 0, 1, 3, 7
measure: 24,25(OH)2D3 level
timeFrame: Day 0, 1, 3, 7
measure: 3-epi-25(OH)D3 level
timeFrame: Day 0, 1, 3, 7
measure: 25(OH)D2 level
timeFrame: Day 0, 1, 3, 7
measure: D3 level
timeFrame: Day 0, 1, 3, 7
measure: 25(OH)D3/24,25(OH)2D3 ratio
timeFrame: Day 0, 1, 3, 7
measure: 25(OH)D3/1,25(OH)2D3 ratio
timeFrame: Day 0, 1, 3, 7
measure: Serum free 25(OH)D
timeFrame: Day 0, 1, 3, 7
measure: Serum vitamin D-binding protein
timeFrame: Day 0, 1, 3, 7
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Endocrinology Research Centre, Moscow
Study officials:
affiliation: Endocrinology Research Centre, Moscow
name: Liudmila Rozhinskaya, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.