Hyperglycemia and the Extra-pancreatic Effect of Incretins

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas Solomon, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01749163
First received: December 11, 2012
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

Incretin hormones (GLP-1 and GIP) released from the intestine in response to meal ingestion augment insulin secretion from the pancreas to help maintain glycemic control. Studies in vitro and in vivo have shown that these incretin hormones also have functional effects in other tissues independent of the insulin secretory response. Both GLP-1 and GIP stimulate insulin secretion in a glucose-dependent manner, however the glucose-dependency of their extra-pancreatic effects has not been examined in vivo. By using pancreatic clamp methodology during euglycemic and hyperglycemic conditions we will test the hypothesis that extra-pancreatic effects of GLP-1 and GIP are glucose-dependent.


Condition Intervention
Extra-pancreatic Incretin Effect
Glucose Effectiveness
Biological: Saline
Biological: GIP
Biological: GLP-1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Determining the Extra-pancreatic Effects of Incretin Hormones During Euglycemic and Hyperglycemic Pancreatic Clamps

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Glucose metabolism [ Time Frame: up to 4 hours ] [ Designated as safety issue: No ]
    Pancreatic clamp will be performed including infusion of somatostatin and replacement of basal insulin, glucagon, and growth hormone. During pancreatic clamps, euglycemia (5 mM) will be maintained via exogenous glucose infusion for the first 2-hours, followed by hyperglycemia (+5 mM) for the final 2-hours. An infusion of the stable isotope [U13C]glucose will be performed to assess glucose kinetics. Expired air will be collected for the analysis of [U13C]glucose into 13CO2.

  • Lipid metabolism [ Time Frame: up to 4 hours ] [ Designated as safety issue: No ]
    An infusion of the stable isotope [D5]glycerol will be performed to assess glycerol kinetics.


Secondary Outcome Measures:
  • Endothelial function [ Time Frame: Baseline, 2 hours, and 4 hours ] [ Designated as safety issue: No ]
    Ultrasound Doppler will be used to examine lower and upper limb blood flow and flow-mediated dilation

  • Signaling [ Time Frame: Baseline, 2 hours, and 4 hours ] [ Designated as safety issue: No ]
    Skeletal muscle (vastus lateralis) and subcutaneous abdominal adipose biopsies will be obtained under local anaesthetic by the Bergstrom needle technique. Intracellular signalling related to glucose and lipid metabolism will be measured.


Estimated Enrollment: 16
Study Start Date: September 2012
Study Completion Date: March 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Control
Saline will be coninfused during the pancreatic clamp
Biological: Saline
Experimental: GIP
GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min
Biological: GIP
Experimental: GLP-1
GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min
Biological: GLP-1

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • age 18-60 years
  • BMI 18-30 kg/m2
  • Male
  • Normal glycemic control (fasting glucose <5.6 mM)

Exclusion Criteria:

  • Evidence of chronic disease
  • Smoking
  • Active weight loss (>2 kg in previous 6 months)
  • Treatment with drugs known to affect our outcome varaibles
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01749163

Locations
Denmark
Rigshospitalet
Copenhagen, Capital Region, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Thomas PJ Solomon, PhD Rigshospitalet, Denmark
  More Information

No publications provided

Responsible Party: Thomas Solomon, Senior Researcher, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01749163     History of Changes
Other Study ID Numbers: PancClamp
Study First Received: December 11, 2012
Last Updated: August 25, 2014
Health Authority: Denmark: Ethics Committee

Additional relevant MeSH terms:
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014