Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea (HNF1A-Clamp)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03081676
Recruitment Status : Completed
First Posted : March 16, 2017
Last Update Posted : June 27, 2019
Sponsor:
Information provided by (Responsible Party):
Alexander Christensen, University Hospital, Gentofte, Copenhagen

Tracking Information
First Submitted Date  ICMJE March 10, 2017
First Posted Date  ICMJE March 16, 2017
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE March 8, 2017
Actual Primary Completion Date June 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 15, 2017)
Insulin secretion [ Time Frame: 0-120 minutes ]
Incremental area under the curve (iAUC) for plasma insulin at time 0-60 minutes, time 60-120 minutes and time 0-120 minutes
Change History Complete list of historical versions of study NCT03081676 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2019)
  • 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
  • Maximal insulin secretion [ Time Frame: 120-125 minutes ]
    Arginine maximal insulin secretion test.
  • Maximal glucagon secretion [ Time Frame: 120-125 minutes ]
    Arginine maximal glucagon secretion test.
  • Amount glucose used to maintain the glucose clamp [ Time Frame: 0-120 minutes ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2017)
  • 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
  • Maximal insulin secretion [ Time Frame: 120-125 minutes ]
    Arginine maximal insulin secretion test.
  • Maximal glucagon secretion [ Time Frame: 120-125 minutes ]
    Arginine maximal glucagon secretion test.
  • DPP-4 activity [ Time Frame: 0-120 minutes ]
  • Amount glucose used to maintain the glucose clamp [ Time Frame: 0-130 minutes ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea
Official Title  ICMJE The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Maturity-Onset Diabetes of the Young, Type 3
Intervention  ICMJE
  • Drug: Glimepiride 1Mg Tablet
    Glimepiride
  • Drug: Glucagon-like Peptide-1
    GLP-1 infusion
  • Drug: Glucose-Dependent Insulinotropic Polypeptide
    GIP-infusion
  • Drug: Placebo Oral Tablet
    Placebo
  • Drug: Placebo infusion
    Placebo (saline)
Study Arms  ICMJE
  • Active Comparator: Glimepiride + GIP
    Tablet Glimepiride + infusion of GIP
    Interventions:
    • Drug: Glimepiride 1Mg Tablet
    • Drug: Glucose-Dependent Insulinotropic Polypeptide
  • Active Comparator: Placebo + GIP
    Placebo tablet + infusion of GIP
    Interventions:
    • Drug: Glucose-Dependent Insulinotropic Polypeptide
    • Drug: Placebo Oral Tablet
  • Active Comparator: Glimepiride + GLP-1
    Glimepiride + infusion of GLP-1
    Interventions:
    • Drug: Glimepiride 1Mg Tablet
    • Drug: Glucagon-like Peptide-1
  • Active Comparator: Placebo + GLP-1
    Placebo tablet + infusion of GLP-1
    Interventions:
    • Drug: Glucagon-like Peptide-1
    • Drug: Placebo Oral Tablet
  • Active Comparator: Glimepiride + Placebo
    Glimepiride + infusion of placebo (saline)
    Interventions:
    • Drug: Glimepiride 1Mg Tablet
    • Drug: Placebo infusion
  • Placebo Comparator: Placebo + Placebo
    Placebo tablet + infusion of placebo (saline)
    Interventions:
    • Drug: Placebo Oral Tablet
    • Drug: Placebo infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 15, 2017)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 1, 2018
Actual Primary Completion Date June 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03081676
Other Study ID Numbers  ICMJE H-16038140
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Alexander Christensen, University Hospital, Gentofte, Copenhagen
Study Sponsor  ICMJE University Hospital, Gentofte, Copenhagen
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital, Gentofte, Copenhagen
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP