<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/NCT03751839</url>
  </required_header>
  <id_info>
    <org_study_id>EKNZ 2018-01517</org_study_id>
    <nct_id>NCT03751839</nct_id>
  </id_info>
  <brief_title>Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes</brief_title>
  <acronym>BOLD-1</acronym>
  <official_title>Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Christian Meier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Schleswig-Holstein</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This single center case control study will assess differences in bone structure between women&#xD;
      and men with longstanding type 1 diabetes (diabetes duration&gt;/= 25 years) and healthy&#xD;
      controls.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Based on a cross-sectional approach the investigators aim to assess microstructural,&#xD;
      biomechanical and densitometric bone characteristics in patients with longstanding type 1&#xD;
      diabetes and age- and sex-matches controls. The investigators examine whether the presence of&#xD;
      microvascular disease and/or poor diabetic control is associated with an altered bone&#xD;
      microarchitecture and whether any such effect is independent of bone mineral density.&#xD;
      Furthermore, the investigators aim to look into the relationship between an altered bone&#xD;
      microarchitecture and advanced glycation end product (AGE) formation as well as biochemical&#xD;
      markers of bone formation and bone turnover. The study aims to identify type 1 diabetic&#xD;
      patients with high fracture risk by assessing the discriminatory power of parameters of&#xD;
      cortical and trabecular microstructure measured via high resolution peripheral quantitative&#xD;
      computed tomography (HR-pQCT) of the distal radius and tibia and high resolution quantitative&#xD;
      computed tomography (HR-QCT) of the proximal femur and tibia with and without adjustment for&#xD;
      bone density.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2018</start_date>
  <completion_date type="Actual">July 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Identical diagnostic procedures will be performed in participants with type 1 diabetes and age- and sex-matched controls.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>volumetric bone mineral density in mg hydroxyapatite (HA)/ccm</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>measured by HR-pQCT at the distal radius and tibia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cortical porosity in %</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>measured by HR-pQCT at the distal radius and tibia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>bone stiffness in kilonewton (kN)/mm</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>a measure of bone strength, measured by HR-pQCT at the distal radius and tibia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>failure load in kN</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>a measure of bone strength, measured by HR-pQCT at the distal radius and tibia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>areal bone mineral density of the spine in g/cm2</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>measured by osteodensitometry (DXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>areal bone mineral density of the proximal femur in g/cm2</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>measured by osteodensitometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>areal bone mineral density of the distal radius in g/cm2</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>measured by osteodensitometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>trabecular bone score of the spine</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>a measure of bone texture, measured by osteodensitometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cortical thickness at the mid tibia in cm</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>density weighed cortical thickness at the mid tibia in cm</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>bone marrow adiposity in mg/cm3</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>measured by HR-pQCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker of bone resorption</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker of bone formation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum pentosidine in pmol/m</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum carboxymethyl-lysine (CML) in pmol/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum insulin in mU/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum sclerostin in pg/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum adiponectin in ng/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum insulin like growth factor -1 (IGF1) in nM</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum interleukin 6 (IL6) in pg/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>measurement of serum periostin in ng/ml</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>biochemical marker associated with bone fragility</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">136</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Diagnostic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Biochemical Tests</intervention_name>
    <description>The investigators will perform blood tests in every participant.</description>
    <arm_group_label>Diagnostic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Osteodensitometry</intervention_name>
    <description>The investigators will perform an osteodensitometry in every participant.</description>
    <arm_group_label>Diagnostic</arm_group_label>
    <other_name>dual energy x-ray absorptiometry (DXA scan)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Clinical Tests</intervention_name>
    <description>The investigators perform the following clinical tests: vibration threshold test, monofilament test, chair rise test and timed up and go test in every participant.</description>
    <arm_group_label>Diagnostic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>HR-QCT</intervention_name>
    <description>The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.</description>
    <arm_group_label>Diagnostic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>HR-pQCT</intervention_name>
    <description>The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.</description>
    <arm_group_label>Diagnostic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women and men with longstanding type 1 diabetes (age 40-80 years, BMI 18-37 kg/m2 and&#xD;
             age- and sex matched non-diabetic controls&#xD;
&#xD;
          -  presence of type 1 diabetes for at least 25 years (defined by history of Insulin&#xD;
             treatment)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients unable to give written informed consent, e.g. with severe dementia or&#xD;
             patients not understanding German (or other local language)&#xD;
&#xD;
          -  Any medical or psychiatric condition which would preclude the participant from&#xD;
             adhering to the protocol&#xD;
&#xD;
          -  Idiopathic or premenopausal osteoporosis or coexisting metabolic bone disease (e.g.&#xD;
             Paget´s disease, primary hyperparathyroidism)&#xD;
&#xD;
          -  Previous treatment with osteoporosis medication (bisphosphonates, denosumab) or intake&#xD;
             of medications that are known to affect bone metabolism (e.g. steroids,&#xD;
             anticonvulsants) within 6 months prior to enrollment&#xD;
&#xD;
          -  Patients with medical conditions known to affect bone health ( e.g. metastatic bone&#xD;
             disease, celiac disease, inflammatory bone disease, hypogonadism, thyrotoxicosis,&#xD;
             hypercortisolism, chronic kidney disease stage IV and V (KDIGO), liver dysfunction&#xD;
             (serum aspartate amino transferase (ASAT) &gt;3 times the upper limit of normal)&#xD;
&#xD;
          -  Inability to keep the extremities still for a few minutes of an HR-pQCT examination&#xD;
             (e.g. Parkinson disease, spastic syndrome)&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christian Meier, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel</name>
      <address>
        <city>Basel</city>
        <state>Basel Stadt</state>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>July 24, 2021</last_update_submitted>
  <last_update_submitted_qc>July 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Basel, Switzerland</investigator_affiliation>
    <investigator_full_name>Christian Meier</investigator_full_name>
    <investigator_title>Prof. Dr. med. Christian Meier</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>In the informed consent document participants can choose whether they agree to the further use of their coded data and biochemical material for future research purposes.</ipd_description>
  </patient_data>
  <!-- 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/NCT03751839
org study id: EKNZ 2018-01517
nct id: NCT03751839
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This single center case control study will assess differences in bone structure between women
      and men with longstanding type 1 diabetes (diabetes duration>/= 25 years) and healthy
      controls.
Based on a cross-sectional approach the investigators aim to assess microstructural,
      biomechanical and densitometric bone characteristics in patients with longstanding type 1
      diabetes and age- and sex-matches controls. The investigators examine whether the presence of
      microvascular disease and/or poor diabetic control is associated with an altered bone
      microarchitecture and whether any such effect is independent of bone mineral density.
      Furthermore, the investigators aim to look into the relationship between an altered bone
      microarchitecture and advanced glycation end product (AGE) formation as well as biochemical
      markers of bone formation and bone turnover. The study aims to identify type 1 diabetic
      patients with high fracture risk by assessing the discriminatory power of parameters of
      cortical and trabecular microstructure measured via high resolution peripheral quantitative
      computed tomography (HR-pQCT) of the distal radius and tibia and high resolution quantitative
      computed tomography (HR-QCT) of the proximal femur and tibia with and without adjustment for
      bone density.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Identical diagnostic procedures will be performed in participants with type 1 diabetes and age- and sex-matched controls.
primary purpose: Diagnostic
masking: None (Open Label)
measure: volumetric bone mineral density in mg hydroxyapatite (HA)/ccm
time frame: through study completion, an average of 6 months
description: measured by HR-pQCT at the distal radius and tibia
measure: cortical porosity in %
time frame: through study completion, an average of 6 months
description: measured by HR-pQCT at the distal radius and tibia
measure: bone stiffness in kilonewton (kN)/mm
time frame: through study completion, an average of 6 months
description: a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
measure: failure load in kN
time frame: through study completion, an average of 6 months
description: a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
measure: areal bone mineral density of the spine in g/cm2
time frame: through study completion, an average of 6 months
description: measured by osteodensitometry (DXA)
measure: areal bone mineral density of the proximal femur in g/cm2
time frame: through study completion, an average of 6 months
description: measured by osteodensitometry
measure: areal bone mineral density of the distal radius in g/cm2
time frame: through study completion, an average of 6 months
description: measured by osteodensitometry
measure: trabecular bone score of the spine
time frame: through study completion, an average of 6 months
description: a measure of bone texture, measured by osteodensitometry
measure: cortical thickness at the mid tibia in cm
time frame: through study completion, an average of 6 months
description: the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)
measure: density weighed cortical thickness at the mid tibia in cm
time frame: through study completion, an average of 6 months
description: the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT
measure: bone marrow adiposity in mg/cm3
time frame: through study completion, an average of 6 months
description: measured by HR-pQCT
measure: measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml
time frame: through study completion, an average of 6 months
description: biochemical marker of bone resorption
measure: measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l
time frame: through study completion, an average of 6 months
description: biochemical marker of bone formation
measure: measurement of serum pentosidine in pmol/m
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum carboxymethyl-lysine (CML) in pmol/ml
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum insulin in mU/ml
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum sclerostin in pg/ml
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum adiponectin in ng/ml
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum insulin like growth factor -1 (IGF1) in nM
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum interleukin 6 (IL6) in pg/ml
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
measure: measurement of serum periostin in ng/ml
time frame: through study completion, an average of 6 months
description: biochemical marker associated with bone fragility
arm group label: Diagnostic
arm group type: Experimental
description: The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements.
intervention type: Diagnostic Test
intervention name: Biochemical Tests
description: The investigators will perform blood tests in every participant.
arm group label: Diagnostic
intervention type: Diagnostic Test
intervention name: Osteodensitometry
description: The investigators will perform an osteodensitometry in every participant.
arm group label: Diagnostic
other name: dual energy x-ray absorptiometry (DXA scan)
intervention type: Diagnostic Test
intervention name: Clinical Tests
description: The investigators perform the following clinical tests: vibration threshold test, monofilament test, chair rise test and timed up and go test in every participant.
arm group label: Diagnostic
intervention type: Diagnostic Test
intervention name: HR-QCT
description: The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.
arm group label: Diagnostic
intervention type: Diagnostic Test
intervention name: HR-pQCT
description: The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.
arm group label: Diagnostic
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christian Meier, Prof.
role: Principal Investigator
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Basel, Switzerland
investigator full name: Christian Meier
investigator title: Prof. Dr. med. Christian Meier
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No
ipd description: In the informed consent document participants can choose whether they agree to the further use of their coded data and biochemical material for future research purposes.