Diabetes Mellitus, Type 2DiaMarvNCT05585697
Bone Turnover in Type 2 Diabetes and Non-diabetes Controls (DiaMarv)
An observational study of Diabetes Mellitus, Type 2 and Bone Fragile, run by University of Aarhus at 1 site in Denmark.
Trial summary
Type 2 diabetes (T2D) is related to an increased risk of major fractures which does written in English. The summary is used not only increase society health care costs, but also increase the morbidity and in the recruitment of peer reviewers.: mortality for patients with T2D. Read more about this study
- Who is it for?
- Ages 40 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Bone Fragile
- What is being tested?
- None - crossectional
- How many people
- 52 participants
- Where
- 1 siteDenmark
- Study dates
- 7 Oct 2022to 1 Sep 2023
- 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 40 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: 26 individials with type 2 diabetes and 26 controls without type 2 diabetes
Who may be able to join
- physician diagnosed T2D,
- diabetes duration ≥5 years,
- HbA1c ≥ 48 mmol/mol through the last 2 years
- male gender,
- age > 40 years
- BMI < 35 kg/m2
Show all 10Show fewer
- no diagnosis of T2D
- male gender,
- age > 40 years
- BMI < 35 kg/m2
Who cannot join
- trombocyte count < 100
- treatment with anticoagulants except acetylic acids,
- renal impairment (eGFR <50 ml/min),
- bone metabolic disease
- vitamin D insufficiency
- treatment with antiosteoporotic agents
- Treatment with systemic glucocorticoids
- Tetracycline allergy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Markers of Bone Turnover and Advanced Glycation End Products Measured in the Circulation, Bone Marrow, and Bone Tissue in Individuals With and Without Type 2 Diabetes
Type 2 diabetes (T2D) is related to an increased risk of major fractures which does written in English. The summary is used not only increase society health care costs, but also increase the morbidity and in the recruitment of peer reviewers.: mortality for patients with T2D. Traditional fracture predictors underestimate the risk in T2D. Thus, the bone affection is not caused by decreased bone mineral density but rather by impaired bone quality leading to fragile bone. In diabetes, circulating bone turnover markers are suppressed and advanced glycation endproducts may accumulate in the tissue. The study aims at exploring whether bone turnover in T2D is compromised in the circulation, bone marrow, and bone tissue and whether advanced glycation endproducts accumulate in these tissues. Furthermore, the investigators will assess whether bone turnover markers predict fractures in a cohort of individuals with diabetes. The project will contribute to the knowledge on bone disease in T2D and will ultimately benefit the patients by improving future fracture prevention strategies.
Read the detailed description
3.1 Methods Study 1 is a cross-sectional study in which 26 individuals with T2D and 26 age matched individuals without T2D are examined. The investigators aim to investigate whether a) bone turnover markers are lower in individuals with type 2 diabetes (T2D) compared to persons without T2D based on circulating bone turnover markers, bone turnover markers in the bone marrow and bone turnover measured in bone tissue biopsies b) the levels of advanced glycation end-products (AGEs) in the circulation, bone marrow, bone tissue, and skin in individuals with and without T2D. The investigators hypothesize that the levels of AGEs is lower in all three tissue compartments in individuals with T2D compared to persons without T2D.
The individuals are included and recruited from outpatient clinics, general practitioners, letters based on information from national registries and via media advertisements.
Inclusion criteria for individuals with T2D; physician diagnosed T2D, diabetes duration ≥5 years, HbA1c ≥ 59 mmol/mol through the last 2 years, male gender, age > 40 years, and BMI < 35 kg/m2. Inclusion criteria for individuals without T2D; no diagnosis of T2D, male gender, age > 40 years, and BMI < 35 kg/m2. Exclusion criteria for all participants; trombocyte count < 100, treatment with anticoagulants except acetylic acids, renal impairment (eGFR <50 ml/min), bone metabolic disease, vitamin D insufficiency, treatment with antiosteoporotic agents or systemic glucocorticoids, and tetracycline allergy.
3.11 Methods Fasting morning blood samples will be collected. The participants will undergo a whole body dual energy x-ray absorptiometry (DXA) to investigate body composition (lean and fat mass) and a Jamshidi bone marrow biopsy in which two pieces of bone tissue is collected for measurement of bone turnover and AGES.
3.12. Bone tissue biopsy Before the bone tissue sampling, the bone tissue will be labelled twice by administration of tetracycline. Tetracykline is incorporated in newly formed bone as bands that are visible in a microscope. A histomorphometric analysis is conducted on the bone tissue sample to investigate the indices of bone turnover.
3.13 Measurement of biomarkers From the bone marrow and plasma/serum samples the following is measured Bone resorption markers: CTX and TRAP5b. Bone formation markers: P1NP, Osteocalcin, and Bone specific alkaline phosphatase.
Bone signaling markers: Osteoprotegerin, RANKL, Sclerostin and parathyroid hormone.
3.14. Analysis of the whole body DXA The whole body DXA measures BMD and lean and fat mass. 3.15 Measurement of AGEs Blood serum and bone marrow serum levels of AGEs are measured. For each participant, one bone tissue biopsy is pulverized, and the level of AGEs in the bone tissue estimated by Fourier Transformed Infrared Spectroscopy (FTIR) in collaboration with the Interdisciplinary Nanoscience Center, Aarhus University. Skin autofluorescence will be applied to non-invasively measure levels of AGEs in the skin.
3.16 Statistics Students t-tests will be used to compare levels of bone turnover markers and AGEs between individuals with and without T2D. Bland Altman plots will be used to analyze agreement between measurement of the bone turnover markers and AGEs at the different tissue compartments. Adjustment will be performed using logistic or linear regression dependent on data distribution.
3.1.7 Power calculation The power calculation is based on the bone formation marker, osteocalcin. Plasma osteocalcin levels were in a previous study 14,4 +/- 5,3 ug/l (mean+/-SD).
It is expected that tere will be a 30% lower level of osteocalcin in individuals with T2D compared to individuals without T2D. Based on the above assumptions, the probability of a type 1 error of 0.05, the probability of a type II error of 0.8, and that two marrow aspirations in each group will fail, 26 individuals should be included in each group in order to detect a difference.
3.l.8 Approval The study is approved at the Regional Ethics Committee, Region Midtjylland: 1-10-72-214-21.
- Conditions
- Diabetes Mellitus, Type 2, Bone Fragile
- Being tested
- None - crossectional
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
None - crossectionalOther
None - crossectional
| Study group | Role | What they receive |
|---|---|---|
| Type 2 diabetes or control | Individuals with type 2 diabetes. Expect to include 26. Individuals without type 2 diabetes. Expect to include 26. Receives: Other: None - crossectional |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of Osteocalcin
Circulating bone turnover marker
Measured: 2 years
Secondary outcomes (13)
Plasma concentration of CTX
Circulating bone turnover marker
Measured: 2 years
Plasma concentration of P1NP
Circulating bone turnover marker
Measured: 2 years
Plasma concentration of Sclerostin
Circulating bone turnover marker
Measured: 2 years
Bone marrow serum concentration of P1NP
Circulating bone turnover marker
Measured: 2 years
Bone marrow serum concentration of CTX
Circulating bone turnover marker
Measured: 2 years
Bone marrow serum concentration of Osteocalcin
Circulating bone turnover marker
Measured: 2 years
Bone marrow serum concentration of Sclerostin
Circulating bone turnover marker
Measured: 2 years
serum concentration of penstosidine
Advanced glycation endproduct
Measured: 2 years
bone marrow serum concentration of pentosidine
Advanced glycation endproduct
Measured: 2 years
Bone formation rate in bone tissue
Bone turnover in bone based on histomorphometric analysis
Measured: 2 years
Advanced glycation endproductsproducts in bone
Raman spectroscopy to determine levels of Advanced glycation endproducts in bone tissue
Measured: 2 years
Strenght measure of bone
Nano-indentation of the bone
Measured: 2 years
trabecular separation distance
bone structure measure provided by x-ray nano-CT
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2022
- Study start7 Oct 2022
- Primary completion1 Sep 2023
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- 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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05585697
- Sponsor's protocol ID
- AUH_HOK_2022_1
- Acronym
- DiaMarv
- Status last verified
- Nov 2023
- First submitted
- 14 Oct 2022
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Due to GPRD it may not be possible to share IPD.
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Markers of Bone Turnover and Advanced Glycation End Products Measured in the Circulation, Bone Marrow, and Bone Tissue in Individuals With and Without Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05585697
- Acronym / sponsor ID
- DiaMarv / AUH_HOK_2022_1
- Conditions
- Diabetes Mellitus, Type 2, Bone Fragile
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 7 Oct 2022 (actual)
- Primary completion
- 1 Sep 2023 (actual)
- Study completion
- 1 Sep 2023 (actual)
- First posted
- 19 Oct 2022 (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.
Type 2 diabetes (T2D) is related to an increased risk of major fractures which does written in English. The summary is used not only increase society health care costs, but also increase the morbidity and in the recruitment of peer reviewers.: mortality for patients with T2D. Traditional fracture predictors underestimate the risk in T2D. Thus, the bone affection is not caused by decreased bone mineral density but rather by impaired bone quality leading to fragile bone. In diabetes, circulating bone turnover markers are suppressed and advanced glycation endproducts may accumulate in the tissue. The study aims at exploring whether bone turnover in T2D is compromised in the circulation, bone marrow, and bone tissue and whether advanced glycation endproducts accumulate in these tissues. Furthermore, the investigators will assess whether bone turnover markers predict fractures in a cohort of individuals with diabetes. The project will contribute to the knowledge on bone disease in T2D and will ultimately benefit the patients by improving future fracture prevention strategies.
Detailed description
3.1 Methods Study 1 is a cross-sectional study in which 26 individuals with T2D and 26 age matched individuals without T2D are examined. The investigators aim to investigate whether a) bone turnover markers are lower in individuals with type 2 diabetes (T2D) compared to persons without T2D based on circulating bone turnover markers, bone turnover markers in the bone marrow and bone turnover measured in bone tissue biopsies b) the levels of advanced glycation end-products (AGEs) in the circulation, bone marrow, bone tissue, and skin in individuals with and without T2D. The investigators hypothesize that the levels of AGEs is lower in all three tissue compartments in individuals with T2D compared to persons without T2D.
The individuals are included and recruited from outpatient clinics, general practitioners, letters based on information from national registries and via media advertisements.
Inclusion criteria for individuals with T2D; physician diagnosed T2D, diabetes duration ≥5 years, HbA1c ≥ 59 mmol/mol through the last 2 years, male gender, age > 40 years, and BMI < 35 kg/m2. Inclusion criteria for individuals without T2D; no diagnosis of T2D, male gender, age > 40 years, and BMI < 35 kg/m2. Exclusion criteria for all participants; trombocyte count < 100, treatment with anticoagulants except acetylic acids, renal impairment (eGFR <50 ml/min), bone metabolic disease, vitamin D insufficiency, treatment with antiosteoporotic agents or systemic glucocorticoids, and tetracycline allergy.
3.11 Methods Fasting morning blood samples will be collected. The participants will undergo a whole body dual energy x-ray absorptiometry (DXA) to investigate body composition (lean and fat mass) and a Jamshidi bone marrow biopsy in which two pieces of bone tissue is collected for measurement of bone turnover and AGES.
3.12. Bone tissue biopsy Before the bone tissue sampling, the bone tissue will be labelled twice by administration of tetracycline. Tetracykline is incorporated in newly formed bone as bands that are visible in a microscope. A histomorphometric analysis is conducted on the bone tissue sample to investigate the indices of bone turnover.
3.13 Measurement of biomarkers From the bone marrow and plasma/serum samples the following is measured Bone resorption markers: CTX and TRAP5b. Bone formation markers: P1NP, Osteocalcin, and Bone specific alkaline phosphatase.
Bone signaling markers: Osteoprotegerin, RANKL, Sclerostin and parathyroid hormone.
3.14. Analysis of the whole body DXA The whole body DXA measures BMD and lean and fat mass. 3.15 Measurement of AGEs Blood serum and bone marrow serum levels of AGEs are measured. For each participant, one bone tissue biopsy is pulverized, and the level of AGEs in the bone tissue estimated by Fourier Transformed Infrared Spectroscopy (FTIR) in collaboration with the Interdisciplinary Nanoscience Center, Aarhus University. Skin autofluorescence will be applied to non-invasively measure levels of AGEs in the skin.
3.16 Statistics Students t-tests will be used to compare levels of bone turnover markers and AGEs between individuals with and without T2D. Bland Altman plots will be used to analyze agreement between measurement of the bone turnover markers and AGEs at the different tissue compartments. Adjustment will be performed using logistic or linear regression dependent on data distribution.
3.1.7 Power calculation The power calculation is based on the bone formation marker, osteocalcin. Plasma osteocalcin levels were in a previous study 14,4 +/- 5,3 ug/l (mean+/-SD).
It is expected that tere will be a 30% lower level of osteocalcin in individuals with T2D compared to individuals without T2D. Based on the above assumptions, the probability of a type 1 error of 0.05, the probability of a type II error of 0.8, and that two marrow aspirations in each group will fail, 26 individuals should be included in each group in order to detect a difference.
3.l.8 Approval The study is approved at the Regional Ethics Committee, Region Midtjylland: 1-10-72-214-21.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Type 2 diabetes or control | – | Other: None - crossectionalIndividuals with type 2 diabetes. Expect to include 26. Individuals without type 2 diabetes. Expect to include 26. |
Who may qualify
- Ages
- 40 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 26 individials with type 2 diabetes and 26 controls without type 2 diabetes
Key inclusion criteria (10 listed)
- physician diagnosed T2D,
- diabetes duration ≥5 years,
- HbA1c ≥ 48 mmol/mol through the last 2 years
- male gender,
- age > 40 years
Key exclusion criteria (8 listed)
- trombocyte count < 100
- treatment with anticoagulants except acetylic acids,
- renal impairment (eGFR <50 ml/min),
- bone metabolic disease
- vitamin D insufficiency
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 |
|---|---|---|
| None - crossectionalNone - crossectional | Other | Type 2 diabetes or control |
Primary outcome
Plasma concentration of Osteocalcin
Time frame: 2 years
Circulating bone turnover marker
13 secondary outcomes
Plasma concentration of CTX
Time frame: 2 years
Plasma concentration of P1NP
Time frame: 2 years
Plasma concentration of Sclerostin
Time frame: 2 years
Bone marrow serum concentration of P1NP
Time frame: 2 years
Bone marrow serum concentration of CTX
Time frame: 2 years
Bone marrow serum concentration of Osteocalcin
Time frame: 2 years
Bone marrow serum concentration of Sclerostin
Time frame: 2 years
serum concentration of penstosidine
Time frame: 2 years
bone marrow serum concentration of pentosidine
Time frame: 2 years
Bone formation rate in bone tissue
Time frame: 2 years
Advanced glycation endproductsproducts in bone
Time frame: 2 years
Strenght measure of bone
Time frame: 2 years
trabecular separation distance
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Individual participant dataSharing planned: No. Due to GPRD it may not be possible to share IPD.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Diabetes Mellitus, Type 2 and Bone Fragile, run by University of Aarhus at 1 site in Denmark.
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 10 inclusion and 8 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: finished, as of the sponsor's last update on 29 Nov 2023. 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 Denmark. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentration of Osteocalcin (time frame: 2 years). 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 29 Nov 2023.