NCT05642143

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:

  • 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

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2023

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 4, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 8, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

February 24, 2023

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2026

Completed
Last Updated

February 7, 2024

Status Verified

February 1, 2024

Enrollment Period

3.1 years

First QC Date

November 4, 2022

Last Update Submit

February 5, 2024

Conditions

Type 2 DiabetesBone DiseaseOsteoporosisDiabetic Neuropathy PeripheralAutonomic Neuropathy, Diabetic

Outcome Measures

Primary Outcomes (3)

  • Evaluation of differences in bone microarchitecture between T2D patients with and without previous fractures assessed by HRpQCT.

    Bone microarchitecture is a composite outcome assessed by HRpQCT at radius and tibia: Total volumetric mineral density, Trabecular volumetric mineral density, Cortical volumetric mineral density, Trabecular number, Trabecular thickness, Cortical thickness, Trabecular separation, Cortical porosity, bone stiffness and failure load.

    Through study completion, estimated 3.5 years

  • Differences in Bone material strength index (BMSi) between T2D patients with and without previous fractures measured by microindentation.

    Through study completion, estimated 3.5 years

  • 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).

    Through study completion, estimated 3.5 years

Secondary Outcomes (10)

  • The impact of autonomic neuropathy on bone microarchitecture in T2D assessed by HR-pQCT.

    Through study completion, estimated 3.5 years

  • The impact of autonomic neuropathy on bone material strength in T2D assessed by microindentation.

    Through study completion, estimated 3.5 years

  • The impact of autonomic neuropathy on bone turnover markers in T2D.

    Through study completion, estimated 3.5 years

  • The impact of peripheral neuropathy on bone microarchitecture in T2D assessed by HR-pQCT.

    Through study completion, estimated 3.5 years

  • The impact of peripheral neuropathy on bone material strength in T2D assessed by microindentation.

    Through study completion, estimated 3.5 years

  • +5 more secondary outcomes

Other Outcomes (5)

  • Co-existence of peripheral and autonomic neuropathy

    Through study completion, estimated 3.5 years

  • The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone microarchitecture (assessed by HR-pQCT) in T2D.

    Through study completion, estimated 3.5 years

  • The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone material strength (assessed by microindentation) in T2D.

    Through study completion, estimated 3.5 years

  • +2 more other outcomes

Study Arms (3)

T2D F-/N-

Subjects with T2D and no previous history of any fractures or diabetic neuropathy (n=160)

Diagnostic Test: Dual Energy X-ray Absorbtiometry scanDiagnostic Test: High-resolution peripheral quantitative computed tomographyDiagnostic Test: MicroindentationDiagnostic Test: Thermal perception thresholdsDiagnostic Test: Nerve conduction studiesDiagnostic Test: Composite Autonomic Symptom Score 31Diagnostic Test: Skin biopsies with quantification of intra-epidermal nerve fibre densityDiagnostic Test: Perception Threshold TrackingDiagnostic Test: Assessment of cardiovascular autonomic neuropathyDiagnostic Test: Handgrip strengthDiagnostic Test: Force plate platformDiagnostic Test: Biospecimen collectionDiagnostic Test: Isometric leg extension strengthDiagnostic Test: Michigan Neuropathy Screening Instrument

T2D F+

Subjects with T2D with a previous history of a fracture(s) (any fracture, major osteoporotic fracture (MOF) and peripheral) (n=100)

Diagnostic Test: Dual Energy X-ray Absorbtiometry scanDiagnostic Test: High-resolution peripheral quantitative computed tomographyDiagnostic Test: MicroindentationDiagnostic Test: Thermal perception thresholdsDiagnostic Test: Nerve conduction studiesDiagnostic Test: Composite Autonomic Symptom Score 31Diagnostic Test: Perception Threshold TrackingDiagnostic Test: Assessment of cardiovascular autonomic neuropathyDiagnostic Test: Handgrip strengthDiagnostic Test: Force plate platformDiagnostic Test: Biospecimen collectionDiagnostic Test: Isometric leg extension strengthDiagnostic Test: Michigan Neuropathy Screening Instrument

T2D N+

Subjects with T2D matched by age and sex with severe peripheral (vibration perception threshold (VPT) \> 50) or a history of autonomic neuropathy (n=40)

Diagnostic Test: Dual Energy X-ray Absorbtiometry scanDiagnostic Test: High-resolution peripheral quantitative computed tomographyDiagnostic Test: MicroindentationDiagnostic Test: Thermal perception thresholdsDiagnostic Test: Nerve conduction studiesDiagnostic Test: Composite Autonomic Symptom Score 31Diagnostic Test: Skin biopsies with quantification of intra-epidermal nerve fibre densityDiagnostic Test: Perception Threshold TrackingDiagnostic Test: Assessment of cardiovascular autonomic neuropathyDiagnostic Test: Handgrip strengthDiagnostic Test: Force plate platformDiagnostic Test: Biospecimen collectionDiagnostic Test: Isometric leg extension strengthDiagnostic Test: Michigan Neuropathy Screening Instrument

Interventions

Dual Energy X-ray Absorbtiometry scanDIAGNOSTIC_TEST

Evaluation of body composition and bone mass density

Also known as: DXA
T2D F+T2D F-/N-T2D N+
High-resolution peripheral quantitative computed tomographyDIAGNOSTIC_TEST

High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture.

Also known as: HR-pQCT
T2D F+T2D F-/N-T2D N+
MicroindentationDIAGNOSTIC_TEST

Measures Bone Material Strength Index (BMSi) of cortical bone.

Also known as: Osteoprobe, ActiveLife, Santa Barbara, CA
T2D F+T2D F-/N-T2D N+
Thermal perception thresholdsDIAGNOSTIC_TEST

Heat and cold perception thresholds

Also known as: Quantitative Sensory Testing
T2D F+T2D F-/N-T2D N+
Nerve conduction studiesDIAGNOSTIC_TEST

Nerve conduction and amplitude of sural nerve

Also known as: NCStat-DPN-Check
T2D F+T2D F-/N-T2D N+
Composite Autonomic Symptom Score 31DIAGNOSTIC_TEST

A validated self-assessment questionnaire quantifying the severity and distribution of autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor functions) by scoring 31 clinically selected questions

Also known as: COMPASS 31
T2D F+T2D F-/N-T2D N+
Skin biopsies with quantification of intra-epidermal nerve fibre densityDIAGNOSTIC_TEST

Skin biopsy

Also known as: PGP9.5, antibodies for subsets of ion-channels ect
T2D F-/N-T2D N+
Perception Threshold TrackingDIAGNOSTIC_TEST

Transcutaneous stimulation of large and small nerve fibres using weak electrical currents

Also known as: PTT
T2D F+T2D F-/N-T2D N+
Assessment of cardiovascular autonomic neuropathyDIAGNOSTIC_TEST

Electrocardiographic recordings at rest and during cardiovascular autonomic reflex tests.

Also known as: Vagus device, Medicus Engineering ApS, Aarhus, Denmark
T2D F+T2D F-/N-T2D N+
Handgrip strengthDIAGNOSTIC_TEST

Evaluation of muscle strength

Also known as: Hydraulic dynamometer, Saehan Corporation, Gyungnam, South Korea
T2D F+T2D F-/N-T2D N+
Force plate platformDIAGNOSTIC_TEST

Evaluation of balance while standing still

Also known as: Plux Biosignals, S.A, Arruda dos Vinhos, Portugal
T2D F+T2D F-/N-T2D N+
Biospecimen collectionDIAGNOSTIC_TEST

Biochemistry including bone turnover markers, glycemic status, inflammation markers i.e

Also known as: Blood samples, Urine samples
T2D F+T2D F-/N-T2D N+
Isometric leg extension strengthDIAGNOSTIC_TEST

Evaluation of muscle strength

Also known as: EasyForce Digital Dynamometer
T2D F+T2D F-/N-T2D N+
Michigan Neuropathy Screening InstrumentDIAGNOSTIC_TEST

MNSI is used to assess status of peripheral neuropathy. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes.

Also known as: MNSI
T2D F+T2D F-/N-T2D N+

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

T2D with and without fractures and neuropathy.

You may qualify if:

  • Men and women with minimum 40 years of age.
  • Diagnosis of T2D. At least one of the following criteria must be met at diagnosis:
  • HbA1c ≥ 48 mmol/mol (6,5 %)
  • Plasma glucose ≥ 11,1 mmol/l
  • Fasting plasma glucose ≥7,0 mmol/l Clinical effect of oral antidiabetic medication strengthens the diagnosis.
  • A history of fracture(s) (confirmed by radiographs analyzed by radiologist) following the diabetes diagnosis (T2D F+ group)
  • 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)
  • Signed the informed consent.

You may not qualify if:

  • Severe decreased liver function (Alanin amino-transaminase (ALAT) \>250 U/l, Gamma-Glutamyltransferase (GGT) \>150 U/l).
  • Moderate to severe kidney dysfunction, estimated Glomerular Filtration Rate (eGFR) \<15 mmol/L/1,73m2.
  • Pregnancy or breast feeding.
  • Active malignancy or terminal ill.
  • Previous chemotherapy or immunomodulating treatment
  • Known severe vitamin deficiency
  • Current or previous alcohol- or drug abuse.
  • Not being able to understand Danish written and/or verbally.
  • 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.
  • Participating in other clinical studies utilizing experimental treatment or medication.
  • Subjects with pathologic fractures (defined as fractures due to local tumors, tumor-like lesions, or focal demineralization as visualized on radiographs).
  • 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.
  • Fracture \< 6 month ago
  • Initiation of antiresorptive or bone anabolic drugs \<12 months ago to ensure stable bone turnover markers.
  • History of fractures following the diagnosis of diabetes (T2D F-/N- and T2D N+ groups).
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Steno Diabetes Center Nordjylland

Aalborg, 9000, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples, urine and skin biopsies

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Bone DiseasesOsteoporosisDiabetic Neuropathies

Interventions

Nerve Conduction StudiesBlood Specimen Collection

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesMusculoskeletal DiseasesBone Diseases, MetabolicPeripheral Nervous System DiseasesNeuromuscular DiseasesNervous System DiseasesDiabetes Complications

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, NeurologicalDiagnostic Techniques and ProceduresDiagnosisElectrodiagnosisSpecimen HandlingClinical Laboratory TechniquesPuncturesSurgical Procedures, OperativeInvestigative Techniques

Central Study Contacts

Julie Lindgård Graversen, MD

CONTACT

97663651j.lindgaard@rn.dk

Peter Vestergaard, MD, PhD, Professor

CONTACT

97663673peter.vestergaard@rn.dk

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 4, 2022

First Posted

December 8, 2022

Study Start

February 24, 2023

Primary Completion

April 1, 2026

Study Completion

April 1, 2026

Last Updated

February 7, 2024

Record last verified: 2024-02

Locations

DK(1)