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

Primary Purpose

Type 1 Diabetes Mellitus

Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Biochemical Tests
Osteodensitometry
Clinical Tests
HR-QCT
HR-pQCT
Sponsored by
Christian Meier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Type 1 Diabetes Mellitus

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic

Arm Description

The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements.

Outcomes

Primary Outcome Measures

volumetric bone mineral density in mg hydroxyapatite (HA)/ccm
measured by HR-pQCT at the distal radius and tibia
cortical porosity in %
measured by HR-pQCT at the distal radius and tibia
bone stiffness in kilonewton (kN)/mm
a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
failure load in kN
a measure of bone strength, measured by HR-pQCT at the distal radius and tibia

Secondary Outcome Measures

areal bone mineral density of the spine in g/cm2
measured by osteodensitometry (DXA)
areal bone mineral density of the proximal femur in g/cm2
measured by osteodensitometry
areal bone mineral density of the distal radius in g/cm2
measured by osteodensitometry
trabecular bone score of the spine
a measure of bone texture, measured by osteodensitometry
cortical thickness at the mid tibia in cm
the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)
density weighed cortical thickness at the mid tibia in cm
the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT
bone marrow adiposity in mg/cm3
measured by HR-pQCT
measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml
biochemical marker of bone resorption
measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l
biochemical marker of bone formation
measurement of serum pentosidine in pmol/m
biochemical marker associated with bone fragility
measurement of serum carboxymethyl-lysine (CML) in pmol/ml
biochemical marker associated with bone fragility
measurement of serum insulin in mU/ml
biochemical marker associated with bone fragility
measurement of serum sclerostin in pg/ml
biochemical marker associated with bone fragility
measurement of serum adiponectin in ng/ml
biochemical marker associated with bone fragility
measurement of serum insulin like growth factor -1 (IGF1) in nM
biochemical marker associated with bone fragility
measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l
biochemical marker associated with bone fragility
measurement of serum interleukin 6 (IL6) in pg/ml
biochemical marker associated with bone fragility
measurement of serum periostin in ng/ml
biochemical marker associated with bone fragility

Full Information

First Posted
October 31, 2018
Last Updated
July 24, 2021
Sponsor
Christian Meier
Collaborators
Insel Gruppe AG, University Hospital Bern, University Hospital Schleswig-Holstein, University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT03751839
Brief Title
Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes
Acronym
BOLD-1
Official Title
Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
July 1, 2021 (Actual)
Study Completion Date
July 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christian Meier
Collaborators
Insel Gruppe AG, University Hospital Bern, University Hospital Schleswig-Holstein, University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Identical diagnostic procedures will be performed in participants with type 1 diabetes and age- and sex-matched controls.
Masking
None (Open Label)
Allocation
N/A
Enrollment
136 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic
Arm Type
Experimental
Arm 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(s)
Biochemical Tests
Intervention Description
The investigators will perform blood tests in every participant.
Intervention Type
Diagnostic Test
Intervention Name(s)
Osteodensitometry
Other Intervention Name(s)
dual energy x-ray absorptiometry (DXA scan)
Intervention Description
The investigators will perform an osteodensitometry in every participant.
Intervention Type
Diagnostic Test
Intervention Name(s)
Clinical Tests
Intervention 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.
Intervention Type
Diagnostic Test
Intervention Name(s)
HR-QCT
Intervention Description
The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.
Intervention Type
Diagnostic Test
Intervention Name(s)
HR-pQCT
Intervention Description
The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.
Primary Outcome Measure Information:
Title
volumetric bone mineral density in mg hydroxyapatite (HA)/ccm
Description
measured by HR-pQCT at the distal radius and tibia
Time Frame
through study completion, an average of 6 months
Title
cortical porosity in %
Description
measured by HR-pQCT at the distal radius and tibia
Time Frame
through study completion, an average of 6 months
Title
bone stiffness in kilonewton (kN)/mm
Description
a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
Time Frame
through study completion, an average of 6 months
Title
failure load in kN
Description
a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
Time Frame
through study completion, an average of 6 months
Secondary Outcome Measure Information:
Title
areal bone mineral density of the spine in g/cm2
Description
measured by osteodensitometry (DXA)
Time Frame
through study completion, an average of 6 months
Title
areal bone mineral density of the proximal femur in g/cm2
Description
measured by osteodensitometry
Time Frame
through study completion, an average of 6 months
Title
areal bone mineral density of the distal radius in g/cm2
Description
measured by osteodensitometry
Time Frame
through study completion, an average of 6 months
Title
trabecular bone score of the spine
Description
a measure of bone texture, measured by osteodensitometry
Time Frame
through study completion, an average of 6 months
Title
cortical thickness at the mid tibia in cm
Description
the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)
Time Frame
through study completion, an average of 6 months
Title
density weighed cortical thickness at the mid tibia in cm
Description
the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT
Time Frame
through study completion, an average of 6 months
Title
bone marrow adiposity in mg/cm3
Description
measured by HR-pQCT
Time Frame
through study completion, an average of 6 months
Title
measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml
Description
biochemical marker of bone resorption
Time Frame
through study completion, an average of 6 months
Title
measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l
Description
biochemical marker of bone formation
Time Frame
through study completion, an average of 6 months
Title
measurement of serum pentosidine in pmol/m
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum carboxymethyl-lysine (CML) in pmol/ml
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum insulin in mU/ml
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum sclerostin in pg/ml
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum adiponectin in ng/ml
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum insulin like growth factor -1 (IGF1) in nM
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum interleukin 6 (IL6) in pg/ml
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months
Title
measurement of serum periostin in ng/ml
Description
biochemical marker associated with bone fragility
Time Frame
through study completion, an average of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Meier, Prof.
Organizational Affiliation
University Hospital, Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel
City
Basel
State/Province
Basel Stadt
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.

Learn more about this trial

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

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