Clinical trial NCT03751839: Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes
Official title: Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Insel Gruppe AG, University Hospital Bern
name: University Hospital Schleswig-Holstein
name: University Hospital, Basel, Switzerland
First posted: 2018-11-23
Enrollment: 136
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Identical diagnostic procedures will be performed in participants with type 1 diabetes and age- and sex-matched controls.
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: volumetric bone mineral density in mg hydroxyapatite (HA)/ccm
timeFrame: through study completion, an average of 6 months
measure: cortical porosity in %
timeFrame: through study completion, an average of 6 months
measure: bone stiffness in kilonewton (kN)/mm
timeFrame: through study completion, an average of 6 months
measure: failure load in kN
timeFrame: through study completion, an average of 6 months
Secondary outcomes:
measure: areal bone mineral density of the spine in g/cm2
timeFrame: through study completion, an average of 6 months
measure: areal bone mineral density of the proximal femur in g/cm2
timeFrame: through study completion, an average of 6 months
measure: areal bone mineral density of the distal radius in g/cm2
timeFrame: through study completion, an average of 6 months
measure: trabecular bone score of the spine
timeFrame: through study completion, an average of 6 months
measure: cortical thickness at the mid tibia in cm
timeFrame: through study completion, an average of 6 months
measure: density weighed cortical thickness at the mid tibia in cm
timeFrame: through study completion, an average of 6 months
measure: bone marrow adiposity in mg/cm3
timeFrame: through study completion, an average of 6 months
measure: measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml
timeFrame: through study completion, an average of 6 months
measure: measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l
timeFrame: through study completion, an average of 6 months
measure: measurement of serum pentosidine in pmol/m
timeFrame: through study completion, an average of 6 months
measure: measurement of serum carboxymethyl-lysine (CML) in pmol/ml
timeFrame: through study completion, an average of 6 months
measure: measurement of serum insulin in mU/ml
timeFrame: through study completion, an average of 6 months
measure: measurement of serum sclerostin in pg/ml
timeFrame: through study completion, an average of 6 months
measure: measurement of serum adiponectin in ng/ml
timeFrame: through study completion, an average of 6 months
measure: measurement of serum insulin like growth factor -1 (IGF1) in nM
timeFrame: through study completion, an average of 6 months
measure: measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l
timeFrame: through study completion, an average of 6 months
measure: measurement of serum interleukin 6 (IL6) in pg/ml
timeFrame: through study completion, an average of 6 months
measure: measurement of serum periostin in ng/ml
timeFrame: through study completion, an average of 6 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel
state: Basel Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Christian Meier, Prof.
role: PRINCIPAL_INVESTIGATOR
References: