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Pathophysiological Implications of the Incretin Hormones in Maturity Onset of Diabetes of the Young (MODY)

This study has been completed.
Sponsor:
Collaborators:
University of Copenhagen
Steno Diabetes Center
Information provided by (Responsible Party):
Signe H Østoft, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01342939
First received: April 13, 2011
Last updated: January 14, 2013
Last verified: January 2013
History of Changes
  Purpose

The purpose of this study is to describe the incretin effect and postprandial incretin response in patients with MODY2 and MODY3 and a group of matched healthy subjects. In sulphonyl urea treated subjects the purpose is also to compare the incretin effect with and without treatment. In healthy subjects the purpose is also to investigate the incretin effect under increased levels of endogen incretin hormones.


Condition Intervention
Maturity-onset Diabetes of the Young
 Other: Oral Glucose Tolerance Test (OGTT)
Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)
Dietary Supplement: Meal test
Other: Sitagliptin
Other: Incretin effect on sulphonyl urea treatment

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: Postprandial Secretion of of Incretin Hormones and Incretin Effect in Patients With Maturity-onset Diabetes of the Young (MODY)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • Incretin effect [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
    The difference in insulin responses, as assessed by the area under curve (AUC) for plasma insulin and C-peptide concentrations, during the two different glucose stimuli: OGTT and isoglycemic iv glucose infusion aswell as after a test meal in MODY-patients compared to healthy control subjects.


Secondary Outcome Measures:
  • Plasma GLP1 response [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
    Comparing GLP1 responses of the different experimental days, compared to healthy control subjects.

  • Plasma GIP response [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
    Comparing GIP responses of the different experimental days, compared to healthy control subjects.

  • Plasma glucagon response [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
    Comparing glucagon responses of the different experimental days, compared to healthy control subjects.


Biospecimen Retention:   Samples With DNA

Buffy coat


Enrollment: 31
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
MODY2
Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene.
 Other: Oral Glucose Tolerance Test (OGTT)
50g waterfree glucose dissolved in 300ml water consumed over 5 min.
Other Name: Waterfree glucose, The Pharmacy of the capital region
Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)
20% glucose
Other Name: Glucose infusion, 20%
Dietary Supplement: Meal test
Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)
Other Name: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark)
Other: Incretin effect on sulphonyl urea treatment
Subject with MODY who are treated with sulphonyl urea are investigated without medication break prior to examination.
MODY3
Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene.
 Other: Oral Glucose Tolerance Test (OGTT)
50g waterfree glucose dissolved in 300ml water consumed over 5 min.
Other Name: Waterfree glucose, The Pharmacy of the capital region
Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)
20% glucose
Other Name: Glucose infusion, 20%
Dietary Supplement: Meal test
Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)
Other Name: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark)
Other: Incretin effect on sulphonyl urea treatment
Subject with MODY who are treated with sulphonyl urea are investigated without medication break prior to examination.
Healthy control subjects Other: Oral Glucose Tolerance Test (OGTT)
50g waterfree glucose dissolved in 300ml water consumed over 5 min.
Other Name: Waterfree glucose, The Pharmacy of the capital region
Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)
20% glucose
Other Name: Glucose infusion, 20%
Dietary Supplement: Meal test
Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)
Other Name: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark)
Other: Sitagliptin
Healthy control subject are given an acute dosage of 100mg the evening before the experimental day, and the same morning in order to increase levels of endogen incretin hormones
Other Name: Januvia, 100mg

Detailed Description:

Comparison of of insulin secretion (AUC) during the experimental days. Furthermore a comparison of GIP, GLP1 and glucagon responses as well as plasma glucose levels.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Genetically well-charaterized MODY2 and MODY3 patients at Hagedorn Research Institute/Steno Diabetes Center

Criteria

Inclusion Criteria:

  • Caucasians above 18 years
  • BMI > 19 kg/m2
  • Negative pancreatic beta cell- and glutamate decarboxylase-65(GAD65)- autoantibodies
  • Normal haemoglobin
  • Normal bloodpressure
  • Informed concent

Exclusion Criteria:

  • Known liver disease or affected liver enzymes (ALAT/ASAT >2 x upper normal limit)
  • Nephropathy (see creatinine> 130 μM and / or albuminuria)
  • Treatment with medications that cannot be discontinued for 12 hours
  • Any condition that the investigators feel would interfere with trial participation
  • Pregnancy or lactation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01342939

Locations
Denmark
Diabetes Research Division, Gentofte University Hospital, Niels Andersens vej 65, opgang 40, 2.
Hellerup, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
University of Copenhagen
Steno Diabetes Center
Investigators
Principal Investigator: Signe H Østoft, MD, phd stud Diabetes Research Division, University Hospital Gentofte, Denmark
  More Information

No publications provided

Responsible Party: Signe H Østoft, MD, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01342939     History of Changes
Other Study ID Numbers: MODY-INK, H-1-2010-130
Study First Received: April 13, 2011
Last Updated: January 14, 2013
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by University Hospital, Gentofte, Copenhagen:
Monogenetic diabetes
Diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hormones
Incretins
Sitagliptin
 Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on May 22, 2013