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Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes (BOLD-1)

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ClinicalTrials.gov Identifier: NCT03751839
Recruitment Status : Recruiting
First Posted : November 22, 2018
Last Update Posted : November 22, 2018
Sponsor:
Collaborators:
University Hospital Inselspital, Berne
University of Schleswig-Holstein
University Hospital, Basel, Switzerland
Information provided by (Responsible Party):
Christian Meier, University Hospital, Basel, Switzerland

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Diagnostic Test: Biochemical Tests Diagnostic Test: Osteodensitometry Diagnostic Test: Clinical Tests Diagnostic Test: HR-QCT Diagnostic Test: HR-pQCT Not Applicable

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
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.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Diagnostic
The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements.
Diagnostic Test: Biochemical Tests
The investigators will perform blood tests in every participant.

Diagnostic Test: Osteodensitometry
The investigators will perform an osteodensitometry in every participant.
Other Name: dual energy x-ray absorptiometry (DXA scan)

Diagnostic Test: Clinical Tests
The investigators perform the following clinical tests: vibration threshold test, monofilament test, chair rise test and timed up and go test in every participant.

Diagnostic Test: HR-QCT
The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.

Diagnostic Test: HR-pQCT
The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.




Primary Outcome Measures :
  1. volumetric bone mineral density in mg hydroxyapatite (HA)/ccm [ Time Frame: through study completion, an average of 6 months ]
    measured by HR-pQCT at the distal radius and tibia

  2. cortical porosity in % [ Time Frame: through study completion, an average of 6 months ]
    measured by HR-pQCT at the distal radius and tibia

  3. bone stiffness in kilonewton (kN)/mm [ Time Frame: through study completion, an average of 6 months ]
    a measure of bone strength, measured by HR-pQCT at the distal radius and tibia

  4. failure load in kN [ Time Frame: through study completion, an average of 6 months ]
    a measure of bone strength, measured by HR-pQCT at the distal radius and tibia


Secondary Outcome Measures :
  1. areal bone mineral density of the spine in g/cm2 [ Time Frame: through study completion, an average of 6 months ]
    measured by osteodensitometry (DXA)

  2. areal bone mineral density of the proximal femur in g/cm2 [ Time Frame: through study completion, an average of 6 months ]
    measured by osteodensitometry

  3. areal bone mineral density of the distal radius in g/cm2 [ Time Frame: through study completion, an average of 6 months ]
    measured by osteodensitometry

  4. trabecular bone score of the spine [ Time Frame: through study completion, an average of 6 months ]
    a measure of bone texture, measured by osteodensitometry

  5. cortical thickness at the mid tibia in cm [ Time Frame: through study completion, an average of 6 months ]
    the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)

  6. density weighed cortical thickness at the mid tibia in cm [ Time Frame: through study completion, an average of 6 months ]
    the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT

  7. bone marrow adiposity in mg/cm3 [ Time Frame: through study completion, an average of 6 months ]
    measured by HR-pQCT

  8. measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker of bone resorption

  9. measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker of bone formation

  10. measurement of serum pentosidine in pmol/m [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  11. measurement of serum carboxymethyl-lysine (CML) in pmol/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  12. measurement of serum insulin in mU/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  13. measurement of serum sclerostin in pg/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  14. measurement of serum adiponectin in ng/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  15. measurement of serum insulin like growth factor -1 (IGF1) in nM [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  16. measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  17. measurement of serum interleukin 6 (IL6) in pg/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility

  18. measurement of serum periostin in ng/ml [ Time Frame: through study completion, an average of 6 months ]
    biochemical marker associated with bone fragility



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • women and men with longstanding type 1 diabetes (age 40-80 years, BMI 18-37 kg/m2 and age- and sex matched non-diabetic controls
  • presence of type 1 diabetes for at least 25 years (defined by history of Insulin treatment)

Exclusion Criteria:

  • Patients unable to give written informed consent, e.g. with severe dementia or patients not understanding German (or other local language)
  • Any medical or psychiatric condition which would preclude the participant from adhering to the protocol
  • Idiopathic or premenopausal osteoporosis or coexisting metabolic bone disease (e.g. Paget´s disease, primary hyperparathyroidism)
  • Previous treatment with osteoporosis medication (bisphosphonates, denosumab) or intake of medications that are known to affect bone metabolism (e.g. steroids, anticonvulsants) within 6 months prior to enrollment
  • Patients with medical conditions known to affect bone health ( e.g. metastatic bone disease, celiac disease, inflammatory bone disease, hypogonadism, thyrotoxicosis, hypercortisolism, chronic kidney disease stage IV and V (KDIGO), liver dysfunction (serum aspartate amino transferase (ASAT) >3 times the upper limit of normal)
  • Inability to keep the extremities still for a few minutes of an HR-pQCT examination (e.g. Parkinson disease, spastic syndrome)
  • Pregnant or breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03751839


Contacts
Contact: Christian Meier, Prof. 0041612649797 christian.meier@unibas.ch
Contact: Lilian Sewing, Dr. 0041612649797 Lilian.Sewing@usb.ch

Locations
Switzerland
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel Recruiting
Basel, Basel Stadt, Switzerland, 4031
Contact: Christian Meier, Prof.    0041612649797    christian.meier@unibas.ch   
Contact: Lilian Sewing, Dr.    0041612649797    Lilian.Sewing@usb.ch   
Sponsors and Collaborators
Christian Meier
University Hospital Inselspital, Berne
University of Schleswig-Holstein
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Christian Meier, Prof. University Hospital, Basel, Switzerland

Responsible Party: Christian Meier, Prof. Dr. med. Christian Meier, University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03751839     History of Changes
Other Study ID Numbers: EKNZ 2018-01517
First Posted: November 22, 2018    Key Record Dates
Last Update Posted: November 22, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan 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.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases