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HyperglycemiaPhase 1NCT00393445

Exendin(9-39)Amide as a Glucagon-like Peptide-1 (GLP-1) Receptor Antagonist in Humans

A Phase 1 study testing GLP-1 and Exendin(9-39) 300, GLP-1 and Exendin(9-39) 600 and GLP-1 and Exendin(9-39) 900 in people with Hyperglycemia, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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%. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Hyperglycemia
What is being tested?
GLP-1 and Exendin(9-39) 300, GLP-1 and Exendin(9-39) 600 and GLP-1 and Exendin(9-39) 900
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteGermany
Study dates
Nov 2006to May 2007
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 18Show fewer
  • 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
  • Polymorphonuclears < 1500/µL at inclusion or platelet count < 100,000/μL at screening and baseline.
  • Evidence of liver disease as indicated by abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin.
  • History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Ludwig Maximilians University, Clinical Research Unit

    Munich, D-81377

Other trials in Germany

About this study

Official title: 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

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%.

Read the detailed description

Following a meal, gut-produced incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the circulation. GLP-1 and GIP, the two dominant incretin hormones, are part of a natural endogenous system involved in maintaining glucose homeostasis. In the presence of normal or elevated, but not low, glucose concentration, both GLP-1 and GIP increase insulin secretion from pancreatic islet beta-cells (β-cells). GLP-1 also lowers glucagon secretion from pancreatic alpha-cells and delays nutrient delivery from the stomach by inhibiting gastric emptying. This rise in insulin concentration enhances glucose clearance in peripheral tissues such as muscle, and the lower glucagon concentration combined with the rise in insulin reduces hepatic glucose production. By enhancing glucose clearance and lowering hepatic glucose production, the post-meal glucose excursion is reduced.

However, the role that each incretin has in glucoregulation is not fully understood. Use of a GLP-1 antagonist, exendin (9-39)NH2, will allow for the assessment of non-GLP-1 incretin's role in glucoregulation. Therefore, it is of great interest to examine the role that specific incretins have in glucoregulation in patients with T2DM.

Exendin(9-39) has been shown a specific and reversible antagonist at the human GLP-1 receptor in vivo. In initial validation studies intravenous exendin(9-39) dose-dependently reduced the insulinotropic action of intravenous GLP-1. The maximal dose of 300 pmol/kg/min used in these studies was sufficient to reduce GLP-1 stimulated insulin plasma levels by about 83%. However, to quantify the contribution of incretin hormones to the incretin effect as stated above a nearly complete inhibition of the GLP-1 action is necessary.

Therefore the purpose of this pilot study is to characterize the dose-response characteristics of exendin(9-39) more completely and to find a dosage which inhibits the insulinotropic action of GLP-1 by at least 95%.

Conditions
Hyperglycemia
Being tested
GLP-1 control, GLP-1 and Exendin(9-39) 300, saline control, GLP-1 and Exendin(9-39) 600, GLP-1 and Exendin(9-39) 900
Keywords
GLP-1, Exendin(9-39), Insulin, Glucagon, Human physiology
Medical subject headings
Hyperglycemia, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GLP-1 controlDrug

    Also called GLP-1(7-36)amide

    intravenous infusion of GLP-1

  • GLP-1 and Exendin(9-39) 300Drug

    intravenous infusion of exendin(9-39) at 300 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min

  • saline controlDrug

    intravenous infusion of saline

  • GLP-1 and Exendin(9-39) 600Drug

    intravenous infusion of exendin(9-39) at 600 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min

  • GLP-1 and Exendin(9-39) 900Drug

    intravenous infusion of exendin(9-39) at 900 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min

  • GLP-1 and Exendin(9-39) 1200Drug

    intravenous infusion of exendin(9-39) at 1200 pmol/kg/min during GLP-1 at 0.3 and 0.9 pmol/kg/min

Study groups in NCT00393445
Study groupRoleWhat they receive
Intravenous infusionExperimentalintravenous infusion of test substances
Receives: Drug: GLP-1 control; Drug: GLP-1 and Exendin(9-39) 300; Drug: saline control; Drug: GLP-1 and Exendin(9-39) 600; Drug: GLP-1 and Exendin(9-39) 900; Drug: GLP-1 and Exendin(9-39) 1200

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: within the actual study period

Secondary outcomes (1)

  1. To assess the effect of increasing doses of exendin(9-39) on plasma glucagon levels decreased by intravenous GLP-1 during hyperglycemia

    Measured: within the actual study period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2006 (estimated)
  2. Study startNov 2006
  3. Study completionMay 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00393445
Sponsor's protocol ID
DOF-Ex
Other IDs
DFG Schi 527/1-2
Status last verified
Oct 2011
First submitted
26 Oct 2006
Last updated
4 Oct 2011
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 9525985

  • Schirra 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.

    PubMed 8550855

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GLP-1 and Exendin(9-39) 300, GLP-1 and Exendin(9-39) 600 and GLP-1 and Exendin(9-39) 900 in people with Hyperglycemia, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: within the actual study period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00393445, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2011.

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