Type 1 DiabetesNCT05701254
Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk
An observational study of Type 1 Diabetes and Osteopenia, run by Creighton University at 1 site in United States.
Trial summary
Patients with Type 1 Diabetes Mellitus (T1DM) 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. Read more about this study
- Who is it for?
- Ages 50 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes, Osteopenia, Bone Loss
- What is being tested?
- Transilial bone biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2019to Jan 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: 40 female type 1 diabetics (both fracturing and non-fracturing) and 40 matched healthy female controls. The investigators will enroll an age-matched, healthy, non-diabetic, non-fracturing female control who is 5 years past the onset of menopause. All of our subjects, diabetics and controls, will be Caucasians, free of diagnoses other than diabetes, and all will have DXA T-scores at the femoral neck and/or total hip and/or lumbar spine between -1.0 and -2.5, (i.e. none will have T-scores in the DXA T-score range of osteoporosis).
Who may be able to join
- Criteria for enrollment of female diabetics
- No chronic disease diagnoses that may affect bone, as confirmed by the PI.
- 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.)
- Glomelular Filtration Rate (GFR) \>45 ml/min (Renal Association lower limit for "mild" kidney failure).
- Willingness to sign a consent form.
- Willingness to undergo a transilial bone biopsy incision that yields 2 bone specimens.
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- No abnormalities in clinical blood chemistry measurements (small, age-related decreases in GFR, will be permitted).
- Caucasian
- Criteria for each non-diabetic subject, compared to their matched diabetic:
- Dual-energy x-ray absorptiometry (DXA) measures (BMD, gm/cm) must be within +/- 15% in total hip.
- Body mass index (BMI) must be within +/-10%.
- Age must be within +/- 5 years.
- Caucasian
Who cannot join
- Women who have had Type 1 diabetes for less than 10 years.
- Non-insulin dependent Type 1 diabetic.
- Less than 50 years old.
- Less than 5 years post menopausal.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Creighton University Osteoporosis Research Center
Omaha, Nebraska, 68122
Adam Hornig, 402-559-9116, adam.hornig@unmc.edu
Mohammed Akhter, PhD, 402-280-5019, mohammedakhter@creighton.edu
About this study
Patients with Type 1 Diabetes Mellitus (T1DM) 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
Read the detailed description
The investigators will enroll 40 female, postmenopausal, patients with T1DM, fracturing or non-fracturing, 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.
- Conditions
- Type 1 Diabetes, Osteopenia, Bone Loss, Fractures, Bone
- Being tested
- Transilial bone biopsy
- Keywords
- Bone, Cortical Bone, Mechanical Strength
- Medical subject headings
- Diabetes Mellitus, Type 1, Bone Diseases, Metabolic, Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transilial bone biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Transilial bone biopsy | |
| 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. Receives: Procedure: Transilial bone biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare cortical bone tissue levels of pentosidine (AGE), pyridinoline (normal enzymatic collagen crosslinks), and matrix-bound water between T1DM and controls.
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.
- Pentosidine (PEN) [ratio]. PEN (Pentosidine) from the integrated area ratio of bands 1495 (PEN) cm-1 / 1450 cm-1 (methylene side chains (CH2)).
- Pyrinoline (Pyd) [ratio]. The pyridinoline (Pyd; enzymatic trivalent collagen cross-link) content is calculated as the absorbance height
Measured: 6-8 weeks
Secondary outcomes (1)
Compare cortical bone tissue heterogeneity in nanoindentation measures of modulus and hardness between T1DM and controls.
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.
- Hardness [GPa-giga-pascal-N/m2]
- Modulus [GPa-giga-pascal-N/m2]
Measured: 6- 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2023
- Study start18 Jun 2019
- Primary completionDec 2024 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Creighton University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohammed Akhter, PhD, Principal investigator, Creighton University Osteoporosis Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05701254
- Sponsor's protocol ID
- 1425624-3
- Status last verified
- Sep 2024
- First submitted
- 21 Dec 2022
- Last updated
- 25 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk
- ClinicalTrials.gov ID
- NCT05701254
- Acronym / sponsor ID
- 1425624-3
- Conditions
- Type 1 Diabetes, Osteopenia, Bone Loss, Fractures, Bone
- Keywords
- Bone, Cortical Bone, Mechanical Strength
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Creighton UniversityUniversity, hospital or other
- Study start
- 18 Jun 2019 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 27 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with Type 1 Diabetes Mellitus (T1DM) 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
Detailed description
The investigators will enroll 40 female, postmenopausal, patients with T1DM, fracturing or non-fracturing, 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
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 1 Diabetics | – | Procedure: Transilial bone biopsyAll 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. |
| Non-Type 1 Diabetics | – | Procedure: Transilial bone biopsyAll 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 40 female type 1 diabetics (both fracturing and non-fracturing) and 40 matched healthy female controls. The investigators will enroll an age-matched, healthy, non-diabetic, non-fracturing female control who is 5 years past the onset of menopause. All of our subjects, diabetics and controls, will be Caucasians, free of diagnoses other than diabetes, and all will have DXA T-scores at the femoral neck and/or total hip and/or lumbar spine between -1.0 and -2.5, (i.e. none will have T-scores in the DXA T-score range of osteoporosis).
Key inclusion criteria (13 listed)
- Criteria for enrollment of female diabetics
- No chronic disease diagnoses that may affect bone, as confirmed by the PI.
- 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.)
- Glomelular Filtration Rate (GFR) \>45 ml/min (Renal Association lower limit for "mild" kidney failure).
- Willingness to sign a consent form.
Key exclusion criteria (4 listed)
- Women who have had Type 1 diabetes for less than 10 years.
- Non-insulin dependent Type 1 diabetic.
- Less than 50 years old.
- Less than 5 years post menopausal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transilial bone biopsyThe 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. | Procedure or surgery | Non-Type 1 Diabetics, Type 1 Diabetics |
Primary outcome
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
1 secondary outcome
Compare cortical bone tissue heterogeneity in nanoindentation measures of modulus and hardness between T1DM and controls.
Time frame: 6- 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohammed Akhter, PhD principal investigator
Creighton University Osteoporosis Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes and Osteopenia, run by Creighton University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adam Hornig (402-559-9116, adam.hornig@unmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2024.