Exendin(9-39)Amide as a Glucagon-like Peptide-1 (GLP-1) Receptor Antagonist in Humans
Effect of GLP-1 on Glucose Metabolism in Healthy Subjects and Patients With T2DM. Part 1: A Pilot Study to Assess the Efficacy of Exendin(9-39)Amide as a GLP-1 Receptor Antagonist in Healthy Subjects
2 other identifiers
interventional
6
1 country
1
Brief Summary
The purpose of this study is to determine the dose of the GLP-1 receptor antagonist exendin(9-39) which blocks the insulinotropic action of synthetic GLP-1 by at least 95%.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2006
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2006
CompletedFirst Posted
Study publicly available on registry
October 27, 2006
CompletedStudy Start
First participant enrolled
November 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2007
CompletedOctober 4, 2011
October 1, 2011
October 26, 2006
October 2, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To assess the effect of increasing doses of exendin(9-39) on first and second phase insulin secretion stimulated by intravenous GLP-1 during hyperglycemia
within the actual study period
Secondary Outcomes (1)
To assess the effect of increasing doses of exendin(9-39) on plasma glucagon levels decreased by intravenous GLP-1 during hyperglycemia
within the actual study period
Study Arms (1)
Intravenous infusion
EXPERIMENTALintravenous infusion of test substances
Interventions
intravenous infusion of exendin(9-39) at 300 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min
intravenous infusion of exendin(9-39) at 600 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min
intravenous infusion of exendin(9-39) at 900 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min
intravenous infusion of exendin(9-39) at 1200 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min
Eligibility Criteria
You may qualify if:
- Male or female (postmenopausal, surgically sterile or using double-barrier method of contraception) healthy volunteers
- Age 18-65 years
- Hemoglobin A1c (HbA1c) \< 6%
- Body mass index (BMI) \< 30 kg/m2
- Must have a fasting blood glucose below 100 mg/dl at screening and on all study days
- Able to provide written informed consent prior to study participation
- Able to communicate well with the investigator and comply with the requirements of the study
You may not qualify if:
- Diabetes mellitus
- Fasting triglycerides \> 5.1 mmol/L (\> 450 mg/dL) within the past 4 weeks.
- Treatment with systemic steroids and thyroid hormone
- Patients with any history of gastrointestinal surgery, e.g. partial bowel resections, partial gastric resections, etc.
- Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
- Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
- Significant illness within the two weeks prior to dosing.
- Past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome.
- History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following:
- history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding
- history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
- history or clinical evidence of pancreatic injury or pancreatitis
- history or presence of impaired renal function as indicated by abnormal creatinine or urea values or abnormal urinary constituents (e.g., albuminuria)
- evidence of urinary obstruction or difficulty in voiding at screening
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ludwig-Maximilians - University of Munichlead
- German Research Foundationcollaborator
- Merck Sharp & Dohme LLCcollaborator
Study Sites (1)
Ludwig Maximilians University, Clinical Research Unit
Munich, D-81377, Germany
Related Publications (2)
Schirra J, Sturm K, Leicht P, Arnold R, Goke B, Katschinski M. Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans. J Clin Invest. 1998 Apr 1;101(7):1421-30. doi: 10.1172/JCI1349.
PMID: 9525985RESULTSchirra J, Katschinski M, Weidmann C, Schafer T, Wank U, Arnold R, Goke B. Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest. 1996 Jan 1;97(1):92-103. doi: 10.1172/JCI118411.
PMID: 8550855RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Joerg Schirra, MD
Clinical Research Unit (CRU), Department of Internal Medicine II-Grosshadern, Ludwig-Maximilans-University of Munich
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- DIAGNOSTIC
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr. med.
Study Record Dates
First Submitted
October 26, 2006
First Posted
October 27, 2006
Study Start
November 1, 2006
Study Completion
May 1, 2007
Last Updated
October 4, 2011
Record last verified: 2011-10