the Type ONe dIabetic Bone Collaboration Study

NCT05673837 | Unknown

• 1 other identifier: S-20200192
• Study Type: observational
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

In this cross-sectional clinical study, we will examine the bones of 111 Type 1 Diabetes (T1D) patients and 37 age-matched healthy controls with the aim of describing a T1D Bone Phenotype. The main Objectives of the study is a) to determine if the material properties of the bones are affected in diabetic bone disease and b) to determine if the mitochondrial function in osteoclasts and osteoblasts is impaired in T1D. Secondary end points are c) to establishment of the T1D bone phenotype and d) to investigate if mitochondrial dysfunction in T1D bone cells correlates to changes in gene expression, gene activity, bone remodelling, bone density, microarchitecture, geometry and material properties. Furthermore, in terms of contributing to knowledge on etiology and pathology of type one diabetic bone disease, we will study the predictory value of muscle mass in T1D patients and controls, as well as other characteristics such as heart rate variability (HRV) and AGE content. Furthermore, we will study the epidemiology of osteoporosis and fractures in Danish T1D patients. To assess the material properties of the bones, we will measure the bone mass density (BMD), use High Resolution peripheral Quantitative Computed Tomography (HRpQCT) for assessment of the microarchitecture and finite element analysis of bone strength, and by microindentation, we will obtain direct measures of the strength of the cortical bone of the tibia. Further we will measure bone turnover markers and circulating microRNA and in a subgroup of participants (24 T1D, 12 controls) bone samples will be retrieved for examination of bone histomorphometry (structural and static parameters) and cell samples from blood and bone marrow will be used for in vitro experiments focused on cell differentiation mitochondrial function, as hyperglycemia may affect mitochondrial function. Finally measures of some possible predictors of bone fragility in subjects with T1D are examined (sarcopenia, skin advanced glycation end products (AGE) content, autonomic neuropathy)

Conditions

Osteoporosis Secondary; Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (9)

• Mitochondrial function: oxygen consumption rate (OCR)

  using the Seahorse Xfe96 Analyzer and measurement of glucose uptake of MSCs, OBs and OCs

  baseline

• measurement of glucose uptake of MSCs, OBs and OCs

  using a bioluminescent assay (Glucose-Uptake Glo, Promega)

  baseline

• cell lactate production

  using the Seahorse Xfe96 Analyzer and measurement of glucose uptake of MSCs, OBs and OCs

  baseline

• Bone Material Strength index (BMSi)

  measure of microindentation on tibia by OsteoProbe(TM),. Measure given as index: BMSi. The strength of the bone is higher with higher BMSi measures which measures from approx. 40 to 90 (no unit)

  baseline

• Bone mineral density by DXA

  DXA scan of hip and spine

  baseline

• Spine trabecular bone score (TBS)

  estimated by software of DXA on spine using Hologic Horizon A. Approx. 1000 to 1600 with higher quality of the network with higher values of TBS

  baseline

• Cortical thickness(Ct.Th)

  measured By High Resolution periphery Quantitative Computed Tomography(HRpQCT)

  baseline

• Failure load

  measured Finite Element Analysis by High Resolution periphery Quantitative Computed Tomography(HRpQCT)

  baseline

• volumetric Bone material density (vBMD)

  measured By High Resolution periphery Quantitative Computed Tomography(HRpQCT)

  baseline

Secondary Outcomes (15)

• microRNA and gene network analyses

  baseline

• microarchitecture

  baseline

• Mineralizing surface (MS/BS, %)

  baseline

• Mineral apposition rate (MAR micrometer/day)

  baseline

• Bone formation rate (BFR/BS)

  baseline

Other Outcomes (7)

• Cortical area

  baseline

• Endosteal perimeter

  baseline

• Periosteal perimeter

  baseline

Study Arms (2)

Type 1 Diabetes

111 persons with Type 1 Diabetes since childhood

Controls

37 persons without diabetes

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Type 1 Diabetic subjects recruited from out-patient clinics and internet pages such as Facebook. Controls from community i.e. through advertisement on internet sites such as Facebook

You may qualify if:

• T1D subjects: Clinical diagnosis of T1D \<18 years of age, C-peptide \<200 pmol L-1 at any time point.
• Controls: HbA1c \<44 mmol mol-1

You may not qualify if:

• BMI \< 18.5 kg/m2
• Primary hyperparathyroidism and other calcium metabolic conditions
• Paget's disease and other metabolic bone diseases
• Vitamin D \<25 nM (re-test after vitamin D replacement acceptable)
• Known disorders affecting bone metabolism, e.g. uncontrolled thyrotoxicosis, chronic kidney disease (eGFR \<30 ml min-1), liver dysfunction (alkaline phosphatase higher than twice the upper limit), celiac disease not controlled by diet, known hypogonadism, severe chronic obstructive pulmonary disease, hypopituitarism and Cushing's disease
• Antiresorptive or bone metabolic drugs for the last 12 months
• Use of anabolic steroids in the last 12 months
• History of pancreatitis
• Allergy to the medicines used
• Inability to give informed consent
• Pregnancy

Sponsors & Collaborators

• Odense University Hospital: lead
• Aalborg University Hospital: collaborator
• Steno Diabetes Center Nordjylland: collaborator
• Esbjerg Hospital - University Hospital of Southern Denmark: collaborator
• Aarhus University Hospital: collaborator
• Steno Diabetes Center Odense: collaborator
• Molecular endocrinology department (KMEB): collaborator

Study Sites (1)

Steno Diabetes Center Nordjylland

Aalborg, 9000, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bone samples (from subgroup of 24+12 individuals), bone marrow aspirates(from subgroup of 24+12 individuals), blood samples

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Morten F Nielsen, MD PhD Prof.

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, PhD Student

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: January 6, 2023
• Study Start: December 10, 2021
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: October 31, 2023

Record last verified: 2023-10

Locations

DK (1)