eCaSIS: Study of the Diagnostic Value of Stable Calcium Isotope Profiling in Bone and Calcium Disorders

Sponsor

Universitaire Ziekenhuizen Leuven (Other)

Overall Status

Completed

CT.gov ID

NCT02252679

Collaborator

GEOMAR-Helmholtz Centre for Ocean Research (Other)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether mass spectrometry analysis of stable (non-radioactive) calcium isotopes in plasma or urine samples can help in the diagnosis of bone and calcium disorders.

Condition or Disease	Intervention/Treatment	Phase
Bone Diseases Osteomalacia Osteoporosis

Detailed Description

The aim of this pilot study is to explore the diagnostic value of MC-ICP-MS (multicollector inductively coupled plasma mass spectrometry) or TIMS (thermal ionization mass spectrometry) measurement of endogenous stable calcium isotopes in plasma and urine samples in patients seen during routine clinical care at the outpatient clinics (incl. Center for Metabolic Bone Diseases) of the University Hospitals Leuven.

Study Design

Study Type:

Observational

Actual Enrollment :

54 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Endogenous Calcium Stable Isotope Study (eCaSIS): Evaluation of MC-ICP-MS as a Diagnostic Tool for Metabolic Bone Diseases and Disorders of Calcium Metabolism

Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Dec 1, 2018

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Osteoporosis Postmenopausal women, men > age 50 years, or other patients with well-established causes of secondary osteoporosis (incl. glucocorticoid-induced osteoporosis, transplantation-related osteoporosis, disuse osteoporosis, etc.) N=20 treated with antiresorptive drugs N=10 treated with osteoanabolic drugs (e.g. teriparatide, Forsteo)
Calcium malabsorption N=10 Patients with clinically obvious potential causes of calcium malabsorption (incl. severe vitamin D-deficiency, Scopinaro or other bariatric surgery, exocrine pancreatic insufficiency/steatorrhea, cystic fibrosis, inflammatory bowel disease, celiac disease, anorexia nervosa/eating disorders, malnutrition, etc.), with or without bone pains, muscle weakness and other typical osteomalacia symptoms. Confirmed by 24h urine collection showing calciuria <100 mg/24h.
Various disorders Exploratory, heterogeneous group of calcium-related disorders (incl.hypercalcemia, hypocalcemia, primary/secondary/tertiary hyperparathyroidism, hypoparathyroidism, vitamin D deficiency, X-linked/autosomal dominant hypophosphatemic rickets, familial hypocalciuric hypocalcemia,etc.) N=20
Normal control subjects N=40 Men and women ≤ 40 years recruited from the population

Outcome Measures

Primary Outcome Measures

Likelihood ratio (LR) of urinary calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]
The sensitivity, specificity, positive and negative predictive value of the new test will be compared to expert clinical diagnosis as the gold standard. This diagnosis is established during follow-up and based on clinical observations, bone mineral density results/changes, bone turnover markers and response to treatments.

Secondary Outcome Measures

Likelihood ratio (LR) of plasma calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]
The sensitivity, specificity, positive and negative predictive value of the new test will be compared to expert clinical diagnosis as the gold standard. This diagnosis is established during follow-up and based on clinical observations, BMD results, bone turnover markers and response to treatments.
Area under the receiver-operator curve (AUROC) of calcium δ44/40 Ca (‰) values compared to bone turnover markers, with expert clinical diagnosis as the golden standard [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]
Osteocalcin and bèta-CTx (C-terminal telopeptide of type I collagen) will be measured.

Other Outcome Measures

Inter- and intra-assay variability of plasma and urine calcium δ44/40 Ca (‰) values [follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)]
calcium δ44/40 Ca (‰) values of human bone samples [before and 1 year after kidney transplantation]
Secondary use of bone biopsy samples obtained in the Leuven Bone Biopsy Program (NCT01886950)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

DXA (dual energy X-ray absorptiometry) T-score known clinically to be = or < -2.5 OR presence of low-energy osteoporotic fractures (i.e. excluding those of the skull, fingers and toes) [for osteoporosis and calcium malabsorption patients]