Glucose InfusionGLUBONENCT02213276
The Effect of Glucose on Bone - Direct og Indirect?
A study testing Oral Glucose Tolerance Test (OGTT) and Intravenous Glucose Tolerance Test (IVGTT) in people with Glucose Infusion and Bone Markers, run by University of Aarhus at 1 site in Denmark.
Trial summary
Diabetes is associated with an increased risk of bone fractures, but current predictors of bone fracture seem to underestimate this risk. It is commonly known that increased levels of certain biochemical bone markers predict low-energy fractures, but the pattern of these markers in diabetics still show heterogeneity… Read more about this study
- Who is it for?
- Ages 20 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Glucose Infusion, Bone Markers, Inflammatory Markers
- What is being tested?
- Oral Glucose Tolerance Test (OGTT) and Intravenous Glucose Tolerance Test (IVGTT)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2014to Jul 2017
- Phase
- Interventional
- 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 20 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males
- Aged 20 - 50 years
Who cannot join
- Chronic diseases, including diabetes, but not allergies
- Daily medication use
- Daily dietary supplement use
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Endocrinology and Internal Medicine
Aarhus, Aarhus C, 8000
About this study
Official title: The Effect of Glucose on Bone - Direct or Indirect?
Diabetes is associated with an increased risk of bone fractures, but current predictors of bone fracture seem to underestimate this risk. It is commonly known that increased levels of certain biochemical bone markers predict low-energy fractures, but the pattern of these markers in diabetics still show heterogeneity and inconsistency. Part of the pathology of diabetes is a high blood glucose level, and this can potentially influence bone turnover and thereby bone markers. Chronic inflammation in patients with inflammatory bowel disease is shown to increase bone resorption, and the same may be the case in diabetics. The purpose of this project is to investigate whether glucose has a direct effect on bone markers or an indirect effect through intestinal hormones or inflammatory processes.
Read the detailed description
Background
Previous studies have shown that Diabetes Mellitus type I (DMI) and II (DMII) is associated with an increased risk of bone fracture. Paradoxically DMII patients have higher Bone Mineral Density (BMD) than average, while DMI patients have lower BMD than average. Even the low BMD of DMI cannot fully explain the extent of fractures found. Known risk factors and BMD underestimate the risk of fracture amongst DM patients using the 10 year fracture risk tool 'Fracture Risk Assessment Tool' (FRAX). It is well-known that increased levels of biochemical bone markers predict low-energy fractures. However bone markers in DM patients show both heterogeneity and inconsistency. Because of this, the predictive value of bone markers is still uncertain in DM patients. Part of the pathology of DM is a higher blood glucose level than found in non-diabetics. This high level of blood glucose could potentially influence bone turnover and thereby bone markers. It is, however, still uncertain whether glucose per se influences the fracture risk of DM patients. Among young healthy individuals, an Oral Glucose Tolerance Test (OGTT) reduces the concentration of both resorptive and formative bone markers. This reduction can be counteracted by the somatostatin analogue, octreotide. Therefore the effect of glucose on bone markers may be indirect and linked to gut hormone release. It may also be caused by a direct effect on osteocytes or a change in the chemical configuration of bone markers, which render them undetectable by standard assays. To examine this, we have conducted preliminary in vitro trials where glucose was added to serum. This does not change the level of bone markers and it is therefore unthinkable that glucose per se affects the assay or causes changed bone marker configuration. The effect of an Intravenous Glucose Tolerance Test (IVGTT) on bone markers has never been examined. Subcutaneous and parenteral injection of the gut hormone glucagon-like peptide 2 (GLP-2) dose-dependently reduces resorptive bone markers, while parenteral GLP-2 entails no change in formative bone markers. This shows that GLP-2 has an uncoupled effect on bone turnover, where resorption is inhibited, and formation remains the same.
There is an association between bone turnover, inflammation and glucose. Chronic inflammation in patients with inflammatory bowel disease increases bone resorption through an increase in the Receptor Activator of Nuclear factor Kappa beta Ligand/Osteoprotegrin (RANKL/OPG) ratio, and the same may be the case in DMII. Human endothelial cells augment production of the inflammatory marker MCP-1 when glucose levels are continuously elevated. RANKL also induces MCP-1 production in human osteoclasts. An in vitro trial shows, that at blood glucose level of 24 mM, osteoblasts increases expression of RANKL, production of inflammatory markers, including MCP-1, and expression of mRNA for the formative bone marker osteocalcin. It has not yet been examined whether MCP-1 correlates with formative and resorptive bone markers in vivo. It is therefore still uncertain whether glucose has a direct effect on bone turnover or an indirect effect via. either GLP-2 or inflammatory processes.
Aim
The aim of this project is to examine whether IVGTT reduces bone marker levels in the same degree as OGTT does. Also, we examine whether the effect of the glucose load is direct or indirect through either GLP-2 or inflammatory processes reflected by inflammatory markers.
Perspective
This project will determine whether the effect of glucose on bone markers is direct or indirect. This knowledge can then be used to explore whether glucose is 'the missing link' in the present fracture prediction score for DM patients.
Methods
In this project 12 healthy male subjects will undergo both oral glucose tolerance test and intra venous glucose tolerance test. During the tests bone markers will be measured at different time intervals and compared to each other. Using these methods it is possible to distinguish whether glucose acts directly on bone and bone markers or through an intestinal or inflammatory pathway. Subjects will be recruited from advertising. After signing a consent form, subjects will fill out a questionaire concerning lifestyle (smoking, alcohol, diet and exercise), previous fracture and familiar disposition to DM, osteoporosis and thyroid disease. Bloodpressure, height and weight will be measured.
Statistics
Paired t-test and repeated measurement analysis will be used for the statistical analyses, as well as linear and logistical regression for adjustment for potential confounders.
- Conditions
- Glucose Infusion, Bone Markers, Inflammatory Markers
- Being tested
- Oral Glucose Tolerance Test (OGTT), Intravenous Glucose Tolerance Test (IVGTT)
- Keywords
- Glucose infusion, Bone markers, Inflammatory markers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Glucose Tolerance Test (OGTT)Other
At baseline participants are asked to drink a glucose solution consisting of 75 grams of glucose dissolved in 250 ml of water. Meanwhile and 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours later, blood is collected from an intravenous access, in order to asses primary and secondary outcomes.
Intravenous Glucose Tolerance Test (IVGTT)Other
In this intervention, the participant needs to have two intravenous accesses. In one we infuse an adjustable 20% glucose solution, and try to mimic the glucose profile found in the oral glucose tolerance test. In order to do this, blood glucose is measured every 5 minutes. At baseline and 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours later, blood is collected from another intravenous access, in order to asses primary and secondary outcomes.
| Study group | Role | What they receive |
|---|---|---|
| Healthy males | Experimental | Oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Receives: Other: Oral Glucose Tolerance Test (OGTT); Other: Intravenous Glucose Tolerance Test (IVGTT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The resorptive bone marker S-CTX.
This outcome will be measured for both the oral glucose tolerance test and the intravenous glucose tolerance test, in order to detect differences in bone marker status.
Measured: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
The formative bone marker S-P1NP
This outcome will be measured for both the oral glucose tolerance test and the intravenous glucose tolerance test, in order to detect differences in bone marker status.
Measured: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
Secondary outcomes (4)
S-NTX
Same as for primary outcome.
Measured: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
S-OC
Same as for primary outcome.
Measured: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
RANKL.
Same as for primary outcomes.
Measured: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
Inflammatory markers.
Same as for primary outcomes.
Measured: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionJul 2016 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glucose InfusionStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02213276
- Sponsor's protocol ID
- 2014-e1
- Acronym
- GLUBONE
- Status last verified
- Aug 2014
- First submitted
- 7 Aug 2014
- Last updated
- 10 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Yan X, Wang Z, Westberg-Rasmussen S, Tarbier M, Rathjen T, Tattikota SG, Peck BCE, Kanke M, Oxvig C, Frystyk J, Starup-Linde J, Sethupathy P, Friedlander MR, Gregersen S, Poy MN. Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3749-3755. doi: 10.1210/jc.2017-01365.
PubMed 28973164
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Glucose on Bone - Direct or Indirect?
- ClinicalTrials.gov ID
- NCT02213276
- Acronym / sponsor ID
- GLUBONE / 2014-e1
- Conditions
- Glucose Infusion, Bone Markers, Inflammatory Markers
- Keywords
- Glucose infusion, Bone markers, Inflammatory markers
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 11 Aug 2014 (estimated)
- 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.
Diabetes is associated with an increased risk of bone fractures, but current predictors of bone fracture seem to underestimate this risk. It is commonly known that increased levels of certain biochemical bone markers predict low-energy fractures, but the pattern of these markers in diabetics still show heterogeneity and inconsistency. Part of the pathology of diabetes is a high blood glucose level, and this can potentially influence bone turnover and thereby bone markers. Chronic inflammation in patients with inflammatory bowel disease is shown to increase bone resorption, and the same may be the case in diabetics. The purpose of this project is to investigate whether glucose has a direct effect on bone markers or an indirect effect through intestinal hormones or inflammatory processes.
Detailed description
Background
Previous studies have shown that Diabetes Mellitus type I (DMI) and II (DMII) is associated with an increased risk of bone fracture. Paradoxically DMII patients have higher Bone Mineral Density (BMD) than average, while DMI patients have lower BMD than average. Even the low BMD of DMI cannot fully explain the extent of fractures found. Known risk factors and BMD underestimate the risk of fracture amongst DM patients using the 10 year fracture risk tool 'Fracture Risk Assessment Tool' (FRAX). It is well-known that increased levels of biochemical bone markers predict low-energy fractures. However bone markers in DM patients show both heterogeneity and inconsistency. Because of this, the predictive value of bone markers is still uncertain in DM patients. Part of the pathology of DM is a higher blood glucose level than found in non-diabetics. This high level of blood glucose could potentially influence bone turnover and thereby bone markers. It is, however, still uncertain whether glucose per se influences the fracture risk of DM patients. Among young healthy individuals, an Oral Glucose Tolerance Test (OGTT) reduces the concentration of both resorptive and formative bone markers. This reduction can be counteracted by the somatostatin analogue, octreotide. Therefore the effect of glucose on bone markers may be indirect and linked to gut hormone release. It may also be caused by a direct effect on osteocytes or a change in the chemical configuration of bone markers, which render them undetectable by standard assays. To examine this, we have conducted preliminary in vitro trials where glucose was added to serum. This does not change the level of bone markers and it is therefore unthinkable that glucose per se affects the assay or causes changed bone marker configuration. The effect of an Intravenous Glucose Tolerance Test (IVGTT) on bone markers has never been examined. Subcutaneous and parenteral injection of the gut hormone glucagon-like peptide 2 (GLP-2) dose-dependently reduces resorptive bone markers, while parenteral GLP-2 entails no change in formative bone markers. This shows that GLP-2 has an uncoupled effect on bone turnover, where resorption is inhibited, and formation remains the same.
There is an association between bone turnover, inflammation and glucose. Chronic inflammation in patients with inflammatory bowel disease increases bone resorption through an increase in the Receptor Activator of Nuclear factor Kappa beta Ligand/Osteoprotegrin (RANKL/OPG) ratio, and the same may be the case in DMII. Human endothelial cells augment production of the inflammatory marker MCP-1 when glucose levels are continuously elevated. RANKL also induces MCP-1 production in human osteoclasts. An in vitro trial shows, that at blood glucose level of 24 mM, osteoblasts increases expression of RANKL, production of inflammatory markers, including MCP-1, and expression of mRNA for the formative bone marker osteocalcin. It has not yet been examined whether MCP-1 correlates with formative and resorptive bone markers in vivo. It is therefore still uncertain whether glucose has a direct effect on bone turnover or an indirect effect via. either GLP-2 or inflammatory processes.
Aim
The aim of this project is to examine whether IVGTT reduces bone marker levels in the same degree as OGTT does. Also, we examine whether the effect of the glucose load is direct or indirect through either GLP-2 or inflammatory processes reflected by inflammatory markers.
Perspective
This project will determine whether the effect of glucose on bone markers is direct or indirect. This knowledge can then be used to explore whether glucose is 'the missing link' in the present fracture prediction score for DM patients.
Methods
In this project 12 healthy male subjects will undergo both oral glucose tolerance test and intra venous glucose tolerance test. During the tests bone markers will be measured at different time intervals and compared to each other. Using these methods it is possible to distinguish whether glucose acts directly on bone and bone markers or through an intestinal or inflammatory pathway. Subjects will be recruited from advertising. After signing a consent form, subjects will fill out a questionaire concerning lifestyle (smoking, alcohol, diet and exercise), previous fracture and familiar disposition to DM, osteoporosis and thyroid disease. Bloodpressure, height and weight will be measured.
Statistics
Paired t-test and repeated measurement analysis will be used for the statistical analyses, as well as linear and logistical regression for adjustment for potential confounders.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy males | Experimental | Other: Oral Glucose Tolerance Test (OGTT), Other: Intravenous Glucose Tolerance Test (IVGTT)Oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy males
- Aged 20 - 50 years
Key exclusion criteria (3 listed)
- Chronic diseases, including diabetes, but not allergies
- Daily medication use
- Daily dietary supplement use
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 |
|---|---|---|
| Oral Glucose Tolerance Test (OGTT)At baseline participants are asked to drink a glucose solution consisting of 75 grams of glucose dissolved in 250 ml of water. Meanwhile and 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours later, blood is collected from an intravenous access, in order to asses primary and secondary outcomes. | Other | Healthy males |
| Intravenous Glucose Tolerance Test (IVGTT)In this intervention, the participant needs to have two intravenous accesses. In one we infuse an adjustable 20% glucose solution, and try to mimic the glucose profile found in the oral glucose tolerance test. In order to do this, blood glucose is measured every 5 minutes. At baseline and 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours later, blood is collected from another intravenous access, in order to asses primary and secondary outcomes. | Other | Healthy males |
Primary outcome
The resorptive bone marker S-CTX.
Time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
This outcome will be measured for both the oral glucose tolerance test and the intravenous glucose tolerance test, in order to detect differences in bone marker status.
The formative bone marker S-P1NP
Time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
This outcome will be measured for both the oral glucose tolerance test and the intravenous glucose tolerance test, in order to detect differences in bone marker status.
4 secondary outcomes
S-NTX
Time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
S-OC
Time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
RANKL.
Time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
Inflammatory markers.
Time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2015.
- Derived from this study: PubMed 28973164Yan X, Wang Z, Westberg-Rasmussen S, Tarbier M, Rathjen T, Tattikota SG, Peck BCE, Kanke M, Oxvig C, Frystyk J, Starup-Linde J, Sethupathy P, Friedlander MR, Gregersen S, Poy MN. Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3749-3755. doi: 10.1210/jc.2017-01365.
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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?
A study testing Oral Glucose Tolerance Test (OGTT) and Intravenous Glucose Tolerance Test (IVGTT) in people with Glucose Infusion and Bone Markers, 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 2 inclusion and 3 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 10 Jun 2015. 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?
Results are not available in the source record.
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?
The resorptive bone marker S-CTX. (time frame: Change from baseline (at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02213276, which also lists 1 linked publication.
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 10 Jun 2015.