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Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT03556098
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
Bjørn Hoe, Steno Diabetes Center

Brief Summary:
In the present project the investigators will evaluate whether glucagonotropic properties of the gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may be utilized as a safeguard against hypoglycemia in patients with T1D.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: glucose-dependent insulinotropic peptide Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30] Drug: Saline Solution Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double blinded, randomized, cross-over study
Masking: Double (Participant, Investigator)
Masking Description: The peptides/placebo is prepared, in a randomized fashion, by a laboratory assistant..
Primary Purpose: Basic Science
Official Title: Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes
Estimated Study Start Date : June 15, 2018
Estimated Primary Completion Date : September 1, 2018
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Dextrose

Arm Intervention/treatment
Active Comparator: GIP
Infusion of Glucose-dependent insulinotropic peptide
Drug: glucose-dependent insulinotropic peptide
Infusion of GIP

Active Comparator: GIP[3-30]
Infusion of GIP[3-30]
Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30]
Infusion of GIP antagonist GIP[3-30]

Placebo Comparator: Saline
Infusion of saline
Drug: Saline Solution
Infusion of Saline
Other Name: Placebo




Primary Outcome Measures :
  1. plasma glucose concentration [ Time Frame: At times (minute): - 30, - 15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 225, 240 on study days ]
    plasma glucose excursions and plasma glucose nadir


Secondary Outcome Measures :
  1. Glucose regulatory hormones [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve

  2. Incretin hormones [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve

  3. GIP[3-30] [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    GIP[3-30]. Incremental and total area under the Concentration-Time Curve

  4. Free fatty acids (FFA) [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    Free fatty acids(FFA). Incremental and total area under the Concentration-Time Curve

  5. Blood analysis of paracetamol as an assessment of gastric emptying [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    Assessment of gastric emptying

  6. Fat mRNA [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate changes in fat mRNA

  7. Fat Lipoprotein lipase (LPL) [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate LPL changes in fat

  8. Fat Perilipin 4 [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate Perilipin 4 changes in fat

  9. Fat Fatty acid binding protein 4 (FABP4) [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate Fatty acid binding protein 4 (FABP4) changes in fat

  10. Fat Hormonse-sensitive lipase (HSL) [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate Hormonse-sensitive lipase (HSL) changes in fat

  11. Fat Vascular endothelial growth factor 4 (VEGF-A) [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate Vascular endothelial growth factor 4 (VEGF-A) changes in fat

  12. Fat GIP receptor (GIPR) [ Time Frame: At time 240 minute on study days ]
    Fat biopsy to evaluate GIP receptor (GIPR) changes in fat

  13. Blood pressure [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    Changes in blood pressure, mm Hg

  14. Pulse [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days ]
    Changes in pulse, beats per minute

  15. Hypoglycemia symptom score [ Time Frame: At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 or when clinically relevant, based on the glucose nadir value on study days ]
    Derived from Edinburgh Hypoglycemia Symptom Scale: Self-evaluated 18 symptoms all with a score from 1-7.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Caucasian men
  • Body mass index between 20-27 kg/m^2
  • T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/l (<8,5%)
  • T1D duration between 2-10 years
  • C-peptide negative (C-peptide ≤ 16 ng/mL)
  • Treatment with a stable basal-bolus regimen ≥ 3 months
  • Informed consent

Exclusion Criteria:

  • Anemia (hemoglobin below normal range)
  • Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
  • Nephropathy (serum creatinine above normal range and/or albuminuria)
  • Allergy or intolerance to ingredients included in the standardized meals
  • Prior myocardial infarction or other cardiac events
  • Any physical or psychological condition that the investigator fells would interfere with trial participation
  • Treatment with any glucose-lowering drugs beside insulin

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03556098


Contacts
Contact: Bjørn Hoe, MD 004553634340 bjoern.hoe@regionh.dk
Contact: Filip K Knop, PhD, MD filip.krag.knop.01@regionh.dk

Locations
Denmark
Steno Diabetes Center Copenhagen, Clinical Metabolic Physiology Recruiting
Hellerup, Denmark, 2900
Contact: Bjørn Hoe, MD    004553634340    bjoern.hoe@regionh.dk   
Contact: Filip K Knop, PhD, MD       filip.krag.knop.01@regionh.dk   
Sponsors and Collaborators
Steno Diabetes Center
Investigators
Study Director: Filip K Knop, MD, PhD Steno Diabetes Center Copenhagen, Clinical Metabolic Physiology

Responsible Party: Bjørn Hoe, Medical Doctor, PhD student, Prinicipal Investigator, Steno Diabetes Center
ClinicalTrials.gov Identifier: NCT03556098     History of Changes
Other Study ID Numbers: H-18002707
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bjørn Hoe, Steno Diabetes Center:
Diabetes Mellitus, Type 1
Hypoglycemia
Gastric Inhibitory Polypeptide
Glucagon
Incretin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hormones
Gastric Inhibitory Polypeptide
Incretins
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents