Clinical trial NCT05642143: Deep Phenotyping of Bone Disease in Type 2 Diabetes and Relations to Diabetic Neuropathy
Official title: Deep Phenotyping of Bone Disease in Type 2 Diabetes and Relations to Diabetic Neuropathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type 2 Diabetes
Bone Disease
Osteoporosis
Diabetic Neuropathy Peripheral
Autonomic Neuropathy, Diabetic
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2022-12-08
Enrollment: 300
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: T2D with and without fractures and neuropathy.

Brief summary: Objectives:

The goal of this cross sectional clinical trial is to examine the phenotype of bone disease in type 2 diabetes.The main aims are to:

1. Compare bone microarchitecture, bone biomechanical competence, and bone turnover markers as well as postural control in T2D patients with and without fractures.
2. Examine how autonomic and peripheral neuropathy affects bone microarchitecture, bone material strength and bone turnover markers as well as postural control in T2D.

Methods:

The trial is of cross-sectional design and consists of examinations including

* Blood samples to analyze bone markers, glycemic state i.e.
* Bone scans including dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT) to evaluate Bone Mineral Density, t-score and bone structure.
* Microindentation to evaluate bone material strength
* Skin autofluorescence to measure levels of advanced glycation endproducts (AGEs) in the skin
* Assesment of nerve function (peripheral and autonomic)
* Assesment of postural control, muscle strength and gait

Participants:

A total of 300 type 2 diabetes patients divided to three groups:

* 160 with no history of fractures or diabetic neuropathy
* 100 with a history of fracture(s)
* 40 with autonomic neuropathy or severe peripheral neuropathy


Eligibility criteria: Inclusion Criteria:

1. Men and women with minimum 40 years of age.
2. Diagnosis of T2D. At least one of the following criteria must be met at diagnosis:

   1. HbA1c ≥ 48 mmol/mol (6,5 %)
   2. Plasma glucose ≥ 11,1 mmol/l
   3. Fasting plasma glucose ≥7,0 mmol/l Clinical effect of oral antidiabetic medication strengthens the diagnosis.
3. Diagnosis of diabetes at least one year prior to inclusion of the study to avoid honeymoon diabetes.
4. A history of fracture(s) (confirmed by radiographs analyzed by radiologist) following the diabetes diagnosis (T2D F+ group)
5. Diagnosed with severe peripheral (VPT ≥ 50) or autonomic neuropathy defined by cardiac autonomic reflex tests or severe abnormalities in orthostatic blood pressure (T2D N+ group)
6. Signed the informed consent.
7. Not defined by the exclusion criteria.

Exclusion Criteria:

1. Severe decreased liver function (Alanin amino-transaminase (ALAT) \>250 U/l, Gamma-Glutamyltransferase (GGT) \>150 U/l).
2. Moderate to severe kidney dysfunction, estimated Glomerular Filtration Rate (eGFR) \<15 mmol/L/1,73m2.
3. Pregnancy or breast feeding.
4. Active malignancy or terminal ill.
5. Previous chemotherapy or immunomodulating treatment
6. Known severe vitamin deficiency
7. Current or previous alcohol- or drug abuse.
8. Not being able to understand Danish written and/or verbally.
9. Terms according to investigators judgement that makes subjects unsuitable to participate including lack of ability to understand and comply with instructions and/or reduced physical ability, limiting the ability to participate in the examinations.
10. Participating in other clinical studies utilizing experimental treatment or medication.
11. Subjects with pathologic fractures (defined as fractures due to local tumors, tumor-like lesions, or focal demineralization as visualized on radiographs).
12. Primary hyperparathyroidism, Paget's disease and other metabolic bone diseases, uncontrolled thyrotoxicosis, celiac disease not controlled by diet, known hypogonadism, severe COPD, hypopituitarism, Cushing's disease.
13. Fracture \< 6 month ago
14. Initiation of antiresorptive or bone anabolic drugs \<12 months ago to ensure stable bone turnover markers.
15. History of fractures following the diagnosis of diabetes (T2D F-/N- and T2D N+ groups).
16. History of peripheral or autonomic neuropathy defined by cardiac autonomic reflex tests or severe abnormalities in orthostatic blood pressure (T2D F-/N- group).

Primary outcomes:
measure: Evaluation of differences in bone microarchitecture between T2D patients with and without previous fractures assessed by HRpQCT.
timeFrame: Through study completion, estimated 3.5 years
measure: Differences in Bone material strength index (BMSi) between T2D patients with and without previous fractures measured by microindentation.
timeFrame: Through study completion, estimated 3.5 years
measure: Evaluation of differences in bone turnover markers between T2D patients with and without previous fractures by biochemical analysis of different bone markers (CTX, P1NP, osteocalcin (OC), ucOC, sclerostin, osteoglycin and osteopontin).
timeFrame: Through study completion, estimated 3.5 years
Secondary outcomes:
measure: The impact of autonomic neuropathy on bone microarchitecture in T2D assessed by HR-pQCT.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of autonomic neuropathy on bone material strength in T2D assessed by microindentation.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of autonomic neuropathy on bone turnover markers in T2D.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of peripheral neuropathy on bone microarchitecture in T2D assessed by HR-pQCT.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of peripheral neuropathy on bone material strength in T2D assessed by microindentation.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of peripheral neuropathy on bone turnover markers in T2D.
timeFrame: Through study completion, estimated 3.5 years
measure: Compare postural control between T2D patients with and without fractures assessed by force platform.
timeFrame: Through study completion, estimated 3.5 years
measure: Compare postural control between T2D patients with and without peripheral/autonomic neuropathy.
timeFrame: Through study completion, estimated 3.5 years
measure: Compare muscle mass and strength in T2D patients with and without fractures
timeFrame: Through study completion, estimated 3.5 years
measure: Compare muscle mass and strength in T2D patients with and without neuropathy
timeFrame: Through study completion, estimated 3.5 years
Other outcomes:
measure: Co-existence of peripheral and autonomic neuropathy
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone microarchitecture (assessed by HR-pQCT) in T2D.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone material strength (assessed by microindentation) in T2D.
timeFrame: Through study completion, estimated 3.5 years
measure: The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone turnover markers in T2D.
timeFrame: Through study completion, estimated 3.5 years
measure: The correlation between levels of Advanced Glycation End Products (AGEs) (assessed by skin autofluorescence) and bone material strength (assessed by microindentation).
timeFrame: Through study completion, estimated 3.5 years
Locations:
city: Aalborg
country: Denmark
facility: Steno Diabetes Center Nordjylland
Study officials:
References: