Maturity-Onset Diabetes of the Young, Type 3HNF1A-ClampNCT03081676
The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea
A study testing Glimepiride 1Mg Tablet, Glucagon-like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in people with Maturity-Onset Diabetes of the Young, Type 3, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial summary
The most prevalent monogenetic diabetic subtype is named maturity onset diabetes of the young type (MODY3) or hepatocyte nuclear factor 1α (HNF1A)-diabetes. The aim of this study is to evaluate the effects of supra-physiological levels of GIP and GLP-1, respectively, on insulin and glucagon secretion at fasting plasma… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Maturity-Onset Diabetes of the Young, Type 3
- What is being tested?
- Glimepiride 1Mg Tablet, Glucagon-like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 8 Mar 2017to 1 Jun 2018
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with HNF1A-diabetes verified by genetic testing
- Patients treated with diet or sulphonylurea monotherapy
- Normal haemoglobin (males 8.3-10.5 mmol/l, females 7.3-9.5 mmol/l)
- Informed consent
- FPG ≤6 mmol/l and glycated haemoglobin (HbA1c) ≤43 mmol/mol
- Normal haemoglobin as defined above
- Age ≥18 years
- Informed consent
Who cannot join
- Nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 and/or albuminuria)
- Liver disease (serum alanine aminotransferase (ALT) and/or serum aspartate aminotransferase (AST) above 2 × normal values)
- Pregnancy or breastfeeding
- No family history of type 1 or type 2 diabetes
- Nephropathy (defined above)
- Liver disease (defined above)
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
The most prevalent monogenetic diabetic subtype is named maturity onset diabetes of the young type (MODY3) or hepatocyte nuclear factor 1α (HNF1A)-diabetes. The aim of this study is to evaluate the effects of supra-physiological levels of GIP and GLP-1, respectively, on insulin and glucagon secretion at fasting plasma glucose (FPG) and "post-prandial" PG levels (1.5 × FPG) in patients with HNF1A-diabetes and matched healthy controls treated with or without a low dose of glimepiride (sulphonylurea). In addition, we will evaluate the maximal insulin and glucagon secretory capacity in both groups.
Read the detailed description
A total of 6 experimental days will be performed. The following is an outline of an experimental day:
Participants will meet after a 10-hour fast. A tablet of glimepiride 1.0 mg or placebo will be administered 90 minutes before the initiation of the experiment (-90 minutes) The mean FPG will be calculated from blood samples -105, -100 and -90 minutes. Two intravenous cannulas will be inserted in a cubital vein of each arm. One intravenous cannula will be used for infusions of glucose, arginine and GIP and the other will be used to collect venous blood. The forearm from which blood samples are drawn will be placed in a heating pad (50°C) throughout the experiment for arterialisation of venous blood.
At time 0 minutes, a glucose clamp will be established at the FPG level for 60 minutes and hereafter a post-prandial clamp period of 1.5 × FPG for another 60 minutes. At time 120 minutes, a bolus of 5g of L-arginine (given as 50% arginine HCl) will be infused during 30 seconds. The post-prandial clamp will be maintained for another 10 minutes until time 130 minutes to prevent reactive hypoglycaemia. Throughout the experiment (0-130 minutes) a continuous infusion of either GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min) or placebo (saline) will be administered.
During the experiment PG will be kept stable by a continuous 20%-glucose infusion. The rate of infusion will be regulated according to PG determined by bed-site measurements every 5 minutes. After 60 minutes, a post-prandial clamp will be established by a bolus infusion over one minute using 50%-glucose to target 1.5 × FPG (the amount of glucose to be administered will calculated as follows: (1.5 × FPG - FPG) × 35 mg glucose × weight in kilogram).
- Being tested
- Glimepiride 1Mg Tablet, Glucagon-like Peptide-1, Glucose-Dependent Insulinotropic Polypeptide, Placebo Oral Tablet, Placebo infusion
- Keywords
- Maturity-Onset Diabetes of the Young, Type 3, Glucose-dependent insulinotropic peptide, Glucagon-like-peptide 1, Dipeptidyl peptidase 4, Glimepiride, Sulphonylurea, Glucose clamp, Hepatocyte nuclear factor 1 alpha
- Medical subject headings
- Maturity-Onset Diabetes of the Young, Type 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glimepiride 1Mg TabletDrug
Glimepiride
Glucagon-like Peptide-1Drug
GLP-1 infusion
Glucose-Dependent Insulinotropic PolypeptideDrug
GIP-infusion
Placebo Oral TabletDrug
Placebo
Placebo infusionDrug
Placebo (saline)
| Study group | Role | What they receive |
|---|---|---|
| Glimepiride + GIP | Active comparator | Tablet Glimepiride + infusion of GIP Receives: Drug: Glimepiride 1Mg Tablet; Drug: Glucose-Dependent Insulinotropic Polypeptide |
| Placebo + GIP | Active comparator | Placebo tablet + infusion of GIP Receives: Drug: Glucose-Dependent Insulinotropic Polypeptide; Drug: Placebo Oral Tablet |
| Glimepiride + GLP-1 | Active comparator | Glimepiride + infusion of GLP-1 Receives: Drug: Glimepiride 1Mg Tablet; Drug: Glucagon-like Peptide-1 |
| Placebo + GLP-1 | Active comparator | Placebo tablet + infusion of GLP-1 Receives: Drug: Glucagon-like Peptide-1; Drug: Placebo Oral Tablet |
| Glimepiride + Placebo | Active comparator | Glimepiride + infusion of placebo (saline) Receives: Drug: Glimepiride 1Mg Tablet; Drug: Placebo infusion |
| Placebo + Placebo | Placebo comparator | Placebo tablet + infusion of placebo (saline) Receives: Drug: Placebo Oral Tablet; Drug: Placebo infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin secretion
Incremental area under the curve (iAUC) for insulin (measured as C-peptide) at time 0-60 minutes, time 60-120 minutes and time 0-120 minutes
Measured: 0-120 minutes
Secondary outcomes (4)
Glucagon secretion
Incremental area under the curve (iAUC) for plasma glucagon at time 0-60 minutes, time 60-120 minutes and time 0-120 minutes
Measured: 0-120 minutes
Maximal insulin secretion
Arginine maximal insulin secretion test.
Measured: 120-125 minutes
Maximal glucagon secretion
Arginine maximal glucagon secretion test.
Measured: 120-125 minutes
Amount glucose used to maintain the glucose clamp
Measured: 0-120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2017
- Study start8 Mar 2017
- Primary completion1 Jun 2018
- Study completion1 Jun 2018
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 Maturity-Onset Diabetes of the Young, Type 3Studies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander Christensen, University Hospital, Gentofte, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03081676
- Sponsor's protocol ID
- H-16038140
- Acronym
- HNF1A-Clamp
- Status last verified
- Jun 2019
- First submitted
- 10 Mar 2017
- Last updated
- 27 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Christensen AS, Haedersdal S, Storgaard H, Rose K, Hansen NL, Holst JJ, Hansen T, Knop FK, Vilsboll T. GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1alpha Mutation Carriers. Diabetes. 2020 Sep;69(9):1989-2002. doi: 10.2337/db20-0074. Epub 2020 Jun 9.
PubMed 32518064
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea
- ClinicalTrials.gov ID
- NCT03081676
- Acronym / sponsor ID
- HNF1A-Clamp / H-16038140
- Keywords
- Maturity-Onset Diabetes of the Young, Type 3, Glucose-dependent insulinotropic peptide, Glucagon-like-peptide 1, Dipeptidyl peptidase 4, Glimepiride, Sulphonylurea, Glucose clamp, Hepatocyte nuclear factor 1 alpha
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Study start
- 8 Mar 2017 (actual)
- Primary completion
- 1 Jun 2018 (actual)
- Study completion
- 1 Jun 2018 (actual)
- First posted
- 16 Mar 2017 (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.
The most prevalent monogenetic diabetic subtype is named maturity onset diabetes of the young type (MODY3) or hepatocyte nuclear factor 1α (HNF1A)-diabetes. The aim of this study is to evaluate the effects of supra-physiological levels of GIP and GLP-1, respectively, on insulin and glucagon secretion at fasting plasma glucose (FPG) and "post-prandial" PG levels (1.5 × FPG) in patients with HNF1A-diabetes and matched healthy controls treated with or without a low dose of glimepiride (sulphonylurea). In addition, we will evaluate the maximal insulin and glucagon secretory capacity in both groups.
Detailed description
A total of 6 experimental days will be performed. The following is an outline of an experimental day:
Participants will meet after a 10-hour fast. A tablet of glimepiride 1.0 mg or placebo will be administered 90 minutes before the initiation of the experiment (-90 minutes) The mean FPG will be calculated from blood samples -105, -100 and -90 minutes. Two intravenous cannulas will be inserted in a cubital vein of each arm. One intravenous cannula will be used for infusions of glucose, arginine and GIP and the other will be used to collect venous blood. The forearm from which blood samples are drawn will be placed in a heating pad (50°C) throughout the experiment for arterialisation of venous blood.
At time 0 minutes, a glucose clamp will be established at the FPG level for 60 minutes and hereafter a post-prandial clamp period of 1.5 × FPG for another 60 minutes. At time 120 minutes, a bolus of 5g of L-arginine (given as 50% arginine HCl) will be infused during 30 seconds. The post-prandial clamp will be maintained for another 10 minutes until time 130 minutes to prevent reactive hypoglycaemia. Throughout the experiment (0-130 minutes) a continuous infusion of either GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min) or placebo (saline) will be administered.
During the experiment PG will be kept stable by a continuous 20%-glucose infusion. The rate of infusion will be regulated according to PG determined by bed-site measurements every 5 minutes. After 60 minutes, a post-prandial clamp will be established by a bolus infusion over one minute using 50%-glucose to target 1.5 × FPG (the amount of glucose to be administered will calculated as follows: (1.5 × FPG - FPG) × 35 mg glucose × weight in kilogram).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Glimepiride + GIP | Active comparator | Drug: Glimepiride 1Mg Tablet, Drug: Glucose-Dependent Insulinotropic PolypeptideTablet Glimepiride + infusion of GIP |
| Placebo + GIP | Active comparator | Drug: Glucose-Dependent Insulinotropic Polypeptide, Drug: Placebo Oral TabletPlacebo tablet + infusion of GIP |
| Glimepiride + GLP-1 | Active comparator | Drug: Glimepiride 1Mg Tablet, Drug: Glucagon-like Peptide-1Glimepiride + infusion of GLP-1 |
| Placebo + GLP-1 | Active comparator | Drug: Glucagon-like Peptide-1, Drug: Placebo Oral TabletPlacebo tablet + infusion of GLP-1 |
| Glimepiride + Placebo | Active comparator | Drug: Glimepiride 1Mg Tablet, Drug: Placebo infusionGlimepiride + infusion of placebo (saline) |
| Placebo + Placebo | Placebo comparator | Drug: Placebo Oral Tablet, Drug: Placebo infusionPlacebo tablet + infusion of placebo (saline) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with HNF1A-diabetes verified by genetic testing
- Patients treated with diet or sulphonylurea monotherapy
- Normal haemoglobin (males 8.3-10.5 mmol/l, females 7.3-9.5 mmol/l)
- Informed consent
- FPG ≤6 mmol/l and glycated haemoglobin (HbA1c) ≤43 mmol/mol
Key exclusion criteria (7 listed)
- Nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 and/or albuminuria)
- Liver disease (serum alanine aminotransferase (ALT) and/or serum aspartate aminotransferase (AST) above 2 × normal values)
- Pregnancy or breastfeeding
- No family history of type 1 or type 2 diabetes
- Nephropathy (defined above)
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 |
|---|---|---|
| Glimepiride 1Mg TabletGlimepiride | Drug | Glimepiride + GIP, Glimepiride + GLP-1, Glimepiride + Placebo |
| Glucagon-like Peptide-1GLP-1 infusion | Drug | Glimepiride + GLP-1, Placebo + GLP-1 |
| Glucose-Dependent Insulinotropic PolypeptideGIP-infusion | Drug | Glimepiride + GIP, Placebo + GIP |
| Placebo Oral TabletPlacebo | Drug | Placebo + GIP, Placebo + GLP-1, Placebo + Placebo |
| Placebo infusionPlacebo (saline) | Drug | Glimepiride + Placebo, Placebo + Placebo |
Primary outcome
Insulin secretion
Time frame: 0-120 minutes
Incremental area under the curve (iAUC) for insulin (measured as C-peptide) at time 0-60 minutes, time 60-120 minutes and time 0-120 minutes
4 secondary outcomes
Glucagon secretion
Time frame: 0-120 minutes
Maximal insulin secretion
Time frame: 120-125 minutes
Maximal glucagon secretion
Time frame: 120-125 minutes
Amount glucose used to maintain the glucose clamp
Time frame: 0-120 minutes
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 27 Jun 2019.
- Derived from this study: PubMed 32518064Christensen AS, Haedersdal S, Storgaard H, Rose K, Hansen NL, Holst JJ, Hansen T, Knop FK, Vilsboll T. GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1alpha Mutation Carriers. Diabetes. 2020 Sep;69(9):1989-2002. doi: 10.2337/db20-0074. Epub 2020 Jun 9.
- Individual participant dataSharing planned: Undecided
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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 Glimepiride 1Mg Tablet, Glucagon-like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in people with Maturity-Onset Diabetes of the Young, Type 3, run by University Hospital, Gentofte, Copenhagen 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 8 inclusion and 7 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 27 Jun 2019. 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. Some participants in this study may receive a placebo. 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?
Insulin secretion (time frame: 0-120 minutes). 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 NCT03081676, 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 27 Jun 2019.