Free Vitamin D and Steroid Metabolism in Endocrine Disorders (FREEDOM)

Free Fraction Vitamin D Measurements to Improve Understanding of Steroid Metabolism in Endocrine Disorders

This clinical study aims to gain a better understanding of how different forms of vitamin D are processed in the body in healthy individuals, pregnant women, and patients with various hormonal (endocrine) and kidney (renal) disorders. In the long term, this study may provide new insights that could how vitamin D is tested and interpreted in these groups.

Vitamin D has several important roles in the body, such as building strong bones and maintaining calcium balance in the blood. Most vitamin D in the blood circulation is attached/bound to a protein called "vitamin D binding protein" (VDBP), which makes it unavailable for the body to use. A much smaller portion circulates freely in the blood and this is called "free vitamin D". This free form can be directly used by the body.

When your doctor tests your vitamin D levels, this usually refers to total vitamin D (the sum of bound and free vitamin D). However, this total value may not give an accurate indication of your actual vitamin D status, since most of it (the bound part) cannot be used by the body. The purpose of this study is to examine whether "free vitamin D" is a better marker of vitamin D status and if the amount of free vitamin D differs between healthy people, pregnant women, and people with specific endocrine or kidney disorders.

Additionally, this study will look into vitamin D metabolism more detailed, and investigate what different forms of vitamin D exist, how the body processes these, and whether these forms may be related to certain endocrine or kidney conditions.

Study Overview

• Status: Recruiting
• Conditions: Vitamin D; Vitamin D and Calcium Homeostasis
• Intervention / Treatment: Other: Blood draw for the laboratory assessment

• Study Type: Observational
• Enrollment (Estimated): 930

Contacts and Locations

• Study Contact: Name: Nick Narinx, MD; Phone Number: +3216348516; Email: nick.narinx@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals Leuven
    • Contact: Nick Narinx, MD; Phone Number: +3216348516; Email: nick.narinx@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Healthy controls: community sample
• Other cohorts: recruited from UZ Leuven (Academic medical center/tertiairy care center)

Description

1. General inclusion Criteria:

   - 18 years or above

2. General exclusion Criteria:

   • Below 18 years of age
   • Individuals incapable of providing informed consent

3. Cohort inclusion criteria

   • Obesity: BMI ≥ 25 kg/m2
   • Chronic Kidney Disease: ≥ CKD stage 3a (eGFR < 60 mL/min/1.73m2)
   • Pregnancy: in trimester 1 of pregnancy
   • Primary hyperparathyroidism: diagnosis at UZ Leuven and scheduled for parathyroidectomy at UZ Leuven
   • Complex calcium and phosphate disorders: diagnosis at UZ Leuven

4. Cohort exclusion criteria

   • Healthy controls: BMI below 18 kg/m² or above 25 kg/m², pregnancy, chronic kidney disease (independent of staging), primary hyperparathyroidism and vitamin D and/or calcium supplementation
   • Obesity: chronic kidney disease (independent of staging), pregnancy, primary hyperparathyroidism
   • Chronic Kidney Disease: BMI below 18 kg/m² or above 30 kg/m², pregnancy, primary hyperparathyroidism
   • Pregnancy: BMI below 18 kg/m² or above 30 kg/m², chronic kidney disease (independent of staging), primary hyperparathyroidism
   • Primary hyperparathyroidism: BMI below 18 kg/m² or above 30 kg/m², pregnancy, chronic kidney disease (independent of staging), secondary hyperparathyroidism

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Controls; 264 individuals, consisting of;132 men132 women; Intervention - Single venous blood draw	Other: Blood draw for the laboratory assessment; Blood draw for the laboratory assessment
Obesity; 132 individuals with obesity, subgrouped according to obesity class33 individuals with overweight, BMI 25.0-29.9 kg/m²33 individuals in obesity class I BMI 30.0-34.9 kg/m²33 individuals in obesity class II BMI 35.0-39.9 kg/m²33 individuals in obesity class III BMI equal to or greater than 40.0 kg/m²; Intervention - Single venous blood draw	Other: Blood draw for the laboratory assessment; Blood draw for the laboratory assessment
Chronic Kidney Disease; 132 individuals with chronic kidney disease (CKD), subgrouped according to CKD staging;33 individuals in class 3a, eGFR 45 - 59 mL/min/1.73m²33 individuals in class 3b, eGFR 30 - 44 mL/min/1.73m²33 individuals in class 4, eGFR 15 - 29 mL/min/1.73m²33 individuals in class 5, eGFR <15 mL/min/1.73m²; Intervention - Single venous blood draw	Other: Blood draw for the laboratory assessment; Blood draw for the laboratory assessment
Pregnancy; 132 pregnant women;- recruited during the first trimester of pregnancy; InterventionVenous blood drawAt 4 timepoints: trimester 1 (week 1-12) , trimester 2 (week 13-27), trimester 3 (week 28-40) and 4-6 weeks after delivery	Other: Blood draw for the laboratory assessment; Blood draw for the laboratory assessment
Primary Hyperparathyroidism; 220 individuals with primary hyperparathyroidismNew diagnosis or previously untreated by surgeryWith an indication for surgery (parathyroidectomy, PTX)); InterventionVenous blood drawAt 3 timepoints: at diagnosis (pre-PTX), day 1 after PTX and post-PTX (during a standard-of-care follow-up visit)	Other: Blood draw for the laboratory assessment; Blood draw for the laboratory assessment
Complex calcium/phosphate disorders; Individuals with complex calcium and phosphate homeostasis disorders; Intervention - Single venous blood draw	Other: Blood draw for the laboratory assessment; Blood draw for the laboratory assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Direct measurement of free 25-hydroxyvitamin D3 levels	1) Direct measurement of free 25-hydroxyvitamin D3, reported as concentration levels per cohort; Reported at baseline; Reported as change versus healthy control group (all cohorts vs healthy control); Reported as change within-cohort (Pregnancy and Primary Hyperparathyroidism).	- Baseline (all cohorts) - Baseline (trimester 1, week 1-12) , trimester 2 (week 13-27), trimester 3 (week 28-40) and 4-6 weeks after delivery (Pregnancy) - Baseline, perioperative and 4-8 weeks after parathyroidectomy (Primary Hyperparathyroidism)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculation of free 25-hydroxyvitamin D3 levels	1) Calculation of free 25-hydroxyvitamin D3, reported as concentration levels per cohort; Reported at baseline; Reported as change versus healthy control group (all cohorts vs healthy control); Reported as change within-cohort (Pregnancy and Primary Hyperparathyroidism).	- Baseline (all cohorts) - Baseline (trimester 1, week 1-12) , trimester 2 (week 13-27), trimester 3 (week 28-40) and 4-6 weeks after delivery (Pregnancy) - Baseline, perioperative and 4-8 weeks after parathyroidectomy (Primary Hyperparathyroidism)
Correlation of measured and calculated free 25-hydroxyvitamin D3 levels	Assessment of correlation between measured (Primary Outcome) and calculated (Secondary Outcome 1) free 25-hydroxyvitamin D3 levels	- Baseline (all cohorts) - Baseline (trimester 1, week 1-12) , trimester 2 (week 13-27), trimester 3 (week 28-40) and 4-6 weeks after delivery (Pregnancy) - Baseline, perioperative and 4-8 weeks after parathyroidectomy (Primary Hyperparathyroidism)
Laboratory assessment of vitamin D metabolite profile	Laboratory assessment of different vitamin D metabolites; 25-hydroxyvitamin D3; 3-epi-hydroxyvitamin D3; 1(alpha).25-dihydroxyvitamin D3; 1(beta).25-dihydroxyvitamin D3; 3-epi-1.25-dihydroxyvitamin D3; 24.25-dihydroxyvitamin D3; 25-hydroxyvitamin D2; 1.25-dihydroxyvitamin D2	- Baseline (all cohorts) - Baseline (trimester 1, week 1-12) , trimester 2 (week 13-27), trimester 3 (week 28-40) and 4-6 weeks after delivery (Pregnancy) - Baseline, perioperative and 4-8 weeks after parathyroidectomy (Primary Hyperparathyroidism)

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Leen Antonio, MD, PhD, University Hospitals Leuven, Department of Endocrinology

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: December 3, 2025
• First Posted (Actual): December 8, 2025

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Vitamin D; Free vitamin D; Free hormone hypothesis
• Additional Relevant MeSH Terms: Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: S67385

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