Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk

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ClinicalTrials.gov Identifier: NCT05701254
Recruitment Status : Recruiting
First Posted : January 27, 2023
Last Update Posted : January 27, 2023
Sponsor:
Information provided by (Responsible Party):
Creighton University

Study Description
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Brief Summary:
Patients with Type 1 Diabetes Mellitus have a higher risk of low-trauma (osteoporotic) fracture that is 7-12 times higher than non-diabetics. The bone density of people with Type 1 Diabetes is higher at the time of fracture than in non-diabetics. This suggests the presence of underlying bone tissue mechanical defects. The potential benefits to participants would be knowledge gained about their bone density and the results of laboratory tests. On a wider scale, there may be general benefits to society because the knowledge gained from this study may help better understand the effects of diabetes on bone health

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Osteoporosis Procedure: Transilial bone biopsy Not Applicable

Detailed Description:
The investigators will enroll 40 female, non-fracturing, postmenopausal, patients with T1DM, who are age 50 and over, and have had diabetes for more than ten years. The investigators will perform 2 transiliac (hip bone) biopsies on each subject, one for mechanical testing, tissue analysis of AGEs, enzymatic crosslinks and bone tissue-bound water in cortical bone, and the other for histomorphometry and high-resolution 3D imaging in trabecular bone. A matched, non-diabetic, healthy control will be enrolled at the time each T1DM is enrolled.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk
Actual Study Start Date : June 18, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : June 1, 2024

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Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Type 1 Diabetics
All participants will complete 4 visits over 6-8 weeks. Visit 1 is a screening visit which includes a physical exam, a bone mineral density scan, a blood draw and an EKG. Visit 2 consists of dispensing the Tetracycline antibiotic required for the bone biopsy. Visit 3 is the bone biopsy and includes a blood draw. Visit 4 is to remove the stitches.
 Procedure: Transilial bone biopsy
The transiliac bone biopsy will be performed on each subject under local anesthesia, and conscious sedation. From one skin incision located ~2cm posterior and inferior to the anterior-superior pelvic spine on one side of the pelvis, the investigators will obtain two iliac bone specimens, each 7.5 mm in diameter, cylindrical in shape, and including both inner and outer cortices and the intervening trabecular bone.
Sham Comparator: Non-Type 1 Diabetics
All participants will complete 4 visits over 6-8 weeks. Visit 1 is a screening visit which includes a physical exam, a bone mineral density scan, a blood draw and an EKG. Visit 2 consists of dispensing the Tetracycline antibiotic required for the bone biopsy. Visit 3 is the bone biopsy and includes a blood draw. Visit 4 is to remove the stitches.
 Procedure: Transilial bone biopsy
The transiliac bone biopsy will be performed on each subject under local anesthesia, and conscious sedation. From one skin incision located ~2cm posterior and inferior to the anterior-superior pelvic spine on one side of the pelvis, the investigators will obtain two iliac bone specimens, each 7.5 mm in diameter, cylindrical in shape, and including both inner and outer cortices and the intervening trabecular bone.


Outcome Measures
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Primary Outcome Measures :
  1. Compare cortical bone tissue levels of pentosidine (AGE), pyridinoline (normal enzymatic collagen crosslinks), and matrix-bound water between T1DM and controls. [ Time Frame: 6-8 weeks ]

    For different advance glycation endproducts (AGEs), a) pentosidine (PEN), b) pyrinoline (Pyd), and c) tissue water (TW), will be measured using Raman spectroscopy technique on bone biopsy tissue obtained from study participants. Raman spectra will be obtained from the embedded block surfaces using a confocal Raman spectrometer (Renishaw InVia Qontor, www.renishaw.de). These spectra will be collected at the interstitial, cement lines, and actively bone forming osteons with evident fluorescent labels. A continuous laser beam with an excitation of 785 nm and power of 10 mW will be focused through a Raman microscope (Leica DM2700M), using the 50x objective, down to a micrometer-sized spot on the sample.

    1. Pentosidine (PEN) [ratio]. PEN (Pentosidine) from the integrated area ratio of bands 1495 (PEN) cm-1 / 1450 cm-1 (methylene side chains (CH2)).
    2. Pyrinoline (Pyd) [ratio]. The pyridinoline (Pyd; enzymatic trivalent collagen cross-link) content is calculated as the absorbance height


Secondary Outcome Measures :
  1. Compare cortical bone tissue heterogeneity in nanoindentation measures of modulus and hardness between T1DM and controls. [ Time Frame: 6- 8 weeks ]

    Bone tissue's hardness and modulus will be quantified by using nanoindentation technique. The nanoindentation is a mechanical/material strength testing technique. The technique has been used in bone tissue from bone biopsies.

    1. Hardness [GPa-giga-pascal-N/m2]
    2. Modulus [GPa-giga-pascal-N/m2]


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Males will not be recruited in order to avoid gender-based confounding effects in the data analysis.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Criteria for enrollment of female diabetics

  1. No chronic disease diagnoses that may affect bone, as confirmed by the PI.
  2. Normal clinical history, physical, and clinical laboratory exam (except for usual complications of a 10+-year diabetic, i.e., ~minimal neuropathy or retinopathy, known, but asymptomatic mild vascular disease, etc.)
  3. GFR >45 ml/min (Renal Association lower limit for "mild" kidney failure).
  4. Willingness to sign a consent form.
  5. Willingness to undergo a transilial bone biopsy incision that yields 2 bone specimens.
  6. No abnormalities in clinical blood chemistry measurements (small, age-related decreases in GFR, will be permitted).
  7. Caucasian

Criteria for each non-diabetic subject, compared to their matched diabetic:

  1. DXA measures (BMD, gm/cm) must be within +/- 15% in total hip.
  2. Body mass index (BMI) must be within +/-10%.
  3. Age must be within +/- 5 years.
  4. Caucasian

Exclusion Criteria:

  1. Women who have had Type 1 diabetes for less than 10 years.
  2. Non-insulin dependent Type 1 diabetic.
  3. Less than 50 years old.
  4. Less than 5 post menopausal.nd have had diabetes for at least 10 years. -
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05701254


Contacts
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Contact: Julie Stubby 402-280-4958 jstubby@creighton.edu
Contact: Joan Lappe 402-280-4646 jmlappe@creighton.edu

Locations
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United States, Nebraska
Creighton University Osteoporosis Research Center Recruiting
Omaha, Nebraska, United States, 68122
Contact: Julie Stubby    402-280-4958    jstubby@creighton.edu   
Contact: Joan Lappe    402-280-4646    jmlappe@creighton.edu   
Sub-Investigator: Laura Armas, MD         
Principal Investigator: Mohammed Akhter, PhD         
Sponsors and Collaborators
Creighton University
Investigators
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Principal Investigator: Mohammed Akhter, PhD Creighton University Osteoporosis Research Center
More Information
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Responsible Party: Creighton University
ClinicalTrials.gov Identifier: NCT05701254    
Other Study ID Numbers: 1425624-3
First Posted: January 27, 2023    Key Record Dates
Last Update Posted: January 27, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Osteoporosis
Diabetes Mellitus
Diabetes Mellitus, Type 1
Osteoporotic Fractures
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Autoimmune Diseases
Immune System Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Fractures, Bone
Wounds and Injuries