<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02252679</url>
  </required_header>
  <id_info>
    <org_study_id>UZ Leuven - s56719</org_study_id>
    <nct_id>NCT02252679</nct_id>
  </id_info>
  <brief_title>Study of the Diagnostic Value of Stable Calcium Isotope Profiling in Bone and Calcium Disorders</brief_title>
  <acronym>eCaSIS</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GEOMAR-Helmholtz Centre for Ocean Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether mass spectrometry analysis of stable&#xD;
      (non-radioactive) calcium isotopes in plasma or urine samples can help in the diagnosis of&#xD;
      bone and calcium disorders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this pilot study is to explore the diagnostic value of MC-ICP-MS (multicollector&#xD;
      inductively coupled plasma mass spectrometry) or TIMS (thermal ionization mass spectrometry)&#xD;
      measurement of endogenous stable calcium isotopes in plasma and urine samples in patients&#xD;
      seen during routine clinical care at the outpatient clinics (incl. Center for Metabolic Bone&#xD;
      Diseases) of the University Hospitals Leuven.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Likelihood ratio (LR) of urinary calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance</measure>
    <time_frame>follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Likelihood ratio (LR) of plasma calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance</measure>
    <time_frame>follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)</time_frame>
    <description>Osteocalcin and bèta-CTx (C-terminal telopeptide of type I collagen) will be measured.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Inter- and intra-assay variability of plasma and urine calcium δ44/40 Ca (‰) values</measure>
    <time_frame>follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>calcium δ44/40 Ca (‰) values of human bone samples</measure>
    <time_frame>before and 1 year after kidney transplantation</time_frame>
    <description>Secondary use of bone biopsy samples obtained in the Leuven Bone Biopsy Program (NCT01886950)</description>
  </other_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">54</enrollment>
  <condition>Bone Diseases</condition>
  <condition>Osteomalacia</condition>
  <condition>Osteoporosis</condition>
  <arm_group>
    <arm_group_label>Osteoporosis</arm_group_label>
    <description>Postmenopausal women, men &gt; 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)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Calcium malabsorption</arm_group_label>
    <description>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 &lt;100 mg/24h.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Various disorders</arm_group_label>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal control subjects</arm_group_label>
    <description>N=40 Men and women ≤ 40 years recruited from the population</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma, serum, spot urine and/or 24h urine collection samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Tertiary care clinical convenience sample Healthy volunteers recruited from the communities&#xD;
        in Leuven and neighbouring cities Siblings, parents or other relatives of patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  DXA (dual energy X-ray absorptiometry) T-score known clinically to be = or &lt; -2.5 OR&#xD;
             presence of low-energy osteoporotic fractures (i.e. excluding those of the skull,&#xD;
             fingers and toes) [for osteoporosis and calcium malabsorption patients]&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  inability to provide written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dirk Vanderschueren, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UZ Leuven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GEOMAR-Helmholtz Centre for Ocean Research</name>
      <address>
        <city>Kiel</city>
        <zip>24148</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Khalil R, Antonio L, Laurent MR, David K, Kim NR, Evenepoel P, Eisenhauer A, Heuser A, Cavalier E, Khosla S, Claessens F, Vanderschueren D, Decallonne B. Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study. Eur J Endocrinol. 2020 Aug;183(2):181-189. doi: 10.1530/EJE-20-0348.</citation>
    <PMID>32454455</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>November 4, 2020</last_update_submitted>
  <last_update_submitted_qc>November 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bone Turnover Markers</keyword>
  <keyword>Calcium Isotopes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Bone Diseases</mesh_term>
    <mesh_term>Osteomalacia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02252679
org study id: UZ Leuven - s56719
nct id: NCT02252679
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
observational model: Case-Control
time perspective: Prospective
measure: Likelihood ratio (LR) of urinary calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance
time frame: follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)
description: 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.
measure: Likelihood ratio (LR) of plasma calcium δ44/40 Ca (‰) values for diagnosing negative skeletal calcium balance
time frame: follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)
description: 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.
measure: 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
time frame: follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)
description: Osteocalcin and bèta-CTx (C-terminal telopeptide of type I collagen) will be measured.
measure: Inter- and intra-assay variability of plasma and urine calcium δ44/40 Ca (‰) values
time frame: follow-up will vary on clinical basis, with expected averages of 1 year (for osteoporosis) to 3 months (for other conditions)
measure: calcium δ44/40 Ca (‰) values of human bone samples
time frame: before and 1 year after kidney transplantation
description: Secondary use of bone biopsy samples obtained in the Leuven Bone Biopsy Program (NCT01886950)
arm group label: Osteoporosis
description: 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)
arm group label: Calcium malabsorption
description: 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.
arm group label: Various disorders
description: 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
arm group label: Normal control subjects
description: N=40 Men and women ≤ 40 years recruited from the population
Plasma, serum, spot urine and/or 24h urine collection samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Dirk Vanderschueren, MD, PhD
role: Principal Investigator
affiliation: UZ Leuven
facility: 
facility: 
country: Belgium
country: Germany
citation: Khalil R, Antonio L, Laurent MR, David K, Kim NR, Evenepoel P, Eisenhauer A, Heuser A, Cavalier E, Khosla S, Claessens F, Vanderschueren D, Decallonne B. Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study. Eur J Endocrinol. 2020 Aug;183(2):181-189. doi: 10.1530/EJE-20-0348.
PMID: 32454455
responsible party type: Sponsor
mesh term: Osteoporosis
mesh term: Bone Diseases
mesh term: Osteomalacia