- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03081676
The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea (HNF1A-Clamp)
Study Overview
Status
Conditions
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Hellerup, Denmark, 2900
- Center for Diabetes Research, Gentofte Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Participants
Ten patients with HNF1A-diabetes and ten matched healthy controls will be recruited. Different inclusion and exclusion criteria applies for the two groups:
Inclusion criteria for HNF1A-patients
- 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
Exclusion criteria for HNF1A-patients
- 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
Inclusion criteria for healthy controls
- FPG ≤6 mmol/l and glycated haemoglobin (HbA1c) ≤43 mmol/mol
- Normal haemoglobin as defined above
- Age ≥18 years
- Informed consent
Exclusion criteria for healthy controls
- No family history of type 1 or type 2 diabetes
- Nephropathy (defined above)
- Liver disease (defined above)
- Pregnancy or breastfeeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Glimepiride + GIP
Tablet Glimepiride + infusion of GIP
|
Glimepiride
GIP-infusion
|
ACTIVE_COMPARATOR: Placebo + GIP
Placebo tablet + infusion of GIP
|
Placebo
GIP-infusion
|
ACTIVE_COMPARATOR: Glimepiride + GLP-1
Glimepiride + infusion of GLP-1
|
Glimepiride
GLP-1 infusion
|
ACTIVE_COMPARATOR: Placebo + GLP-1
Placebo tablet + infusion of GLP-1
|
Placebo
GLP-1 infusion
|
ACTIVE_COMPARATOR: Glimepiride + Placebo
Glimepiride + infusion of placebo (saline)
|
Glimepiride
Placebo (saline)
|
PLACEBO_COMPARATOR: Placebo + Placebo
Placebo tablet + infusion of placebo (saline)
|
Placebo
Placebo (saline)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
0-120 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Glucagon secretion
Time Frame: 0-120 minutes
|
Incremental area under the curve (iAUC) for plasma glucagon at time 0-60 minutes, time 60-120 minutes and time 0-120 minutes
|
0-120 minutes
|
Maximal insulin secretion
Time Frame: 120-125 minutes
|
Arginine maximal insulin secretion test.
|
120-125 minutes
|
Maximal glucagon secretion
Time Frame: 120-125 minutes
|
Arginine maximal glucagon secretion test.
|
120-125 minutes
|
Amount glucose used to maintain the glucose clamp
Time Frame: 0-120 minutes
|
0-120 minutes
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Anti-Arrhythmia Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Incretins
- Glucagon
- Gastric Inhibitory Polypeptide
- Glimepiride
- Glucagon-Like Peptide 1
Other Study ID Numbers
- H-16038140
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Maturity-Onset Diabetes of the Young, Type 3
-
Steno Diabetes Center CopenhagenUniversity of CopenhagenCompletedType 2 Diabetes | Maturity-Onset Diabetes of the Young, Type 3Denmark
-
Haukeland University HospitalUnknownInsulin-dependent Diabetes Mellitus | Maturity-Onset Diabetes of the Young, Type 3 | Maturity Onset Diabetes of the Young, Type 1 | Childhood Diabetes MellitusNorway
-
Taichung Veterans General HospitalNational Health Research Institutes, TaiwanRecruitingDiabetes Complications | Type 2 Diabetes | Maturity-Onset Diabetes of the Young (MODY)Taiwan
-
Imperial College LondonUnknownDiabetes | Type 1 Diabetes | Type 2 Diabetes | Maturity Onset Diabetes of the YoungUnited Kingdom
-
Vanderbilt UniversityCompletedInsulin Resistance | Type 1 Diabetes Mellitus | Maturity-Onset Diabetes of the Young, Type 2 | MODY2United States
-
Assistance Publique - Hôpitaux de ParisCompleted
-
University Hospital, Gentofte, CopenhagenUniversity of Copenhagen; Steno Diabetes Center CopenhagenCompletedMaturity-onset Diabetes of the YoungDenmark
-
University Hospital, Gentofte, CopenhagenNovo Nordisk A/S; University of CopenhagenCompletedMaturity-onset Diabetes of the YoungDenmark
-
United Arab Emirates UniversityNot yet recruitingMaturity-onset Diabetes of the Young | MODY | Monogenic Diabetes
-
Imperial College London Diabetes CentreUnknownDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type 1 | Maturity-onset Diabetes of the YoungUnited Arab Emirates
Clinical Trials on Placebo Oral Tablet
-
EstetraICON Clinical ResearchCompletedVasomotor Symptoms | Menopausal SymptomsUnited States, Canada
-
EicOsis Human Health Inc.RecruitingHealthy SubjectsNew Zealand
-
University of OxfordNovo Nordisk A/SRecruitingDiabetes Mellitus, Type 2United Kingdom
-
Fulcrum TherapeuticsTerminated
-
EicOsis Human Health Inc.CompletedHealthy AdultsUnited States
-
Harmony Biosciences, LLCActive, not recruitingMyotonic Dystrophy 1 | Excessive Daytime SleepinessUnited States, Canada
-
Syntrix Biosystems, Inc.National Institute on Drug Abuse (NIDA); DF/Net ResearchCompletedDiabetic Neuropathies | Neuropathic Pain | Pain, ChronicUnited States
-
The Mind Research NetworkTerminatedSmoking Cessation | Tobacco Use DisorderUnited States
-
Cara Therapeutics, Inc.CompletedChronic Kidney Diseases | PruritusUnited States
-
Sunshine Lake Pharma Co., Ltd.CompletedChronic Hepatitis CChina