Digestive PhysiologyPhase 1NCT00468091
Effects of Exendin(9-39) on Gastroduodenal Motility
A Phase 1 study testing exendin(9-39)amide and atropine in people with Digestive Physiology and Gastrointestinal Motility, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial summary
The purpose of this study in humans is to define the effects of the endogenous hormone GLP-1 on gastroduodenal motility and on endocrine pancreatic secretion by using the specific GLP-1 receptor antagonist exendin(9-39). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Digestive Physiology, Gastrointestinal Motility, Gastrointestinal Hormones
- What is being tested?
- exendin(9-39)amide and atropine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteGermany
- Study dates
- Feb 1999to Sep 2000
- 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
- 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
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich
Munich, 81377
About this study
Official title: Regulation of Antro-pyloro-duodenal and Proximal Gastric Motility by GLP-1: Involvement of Cholinergic Pathways
The purpose of this study in humans is to define the effects of the endogenous hormone GLP-1 on gastroduodenal motility and on endocrine pancreatic secretion by using the specific GLP-1 receptor antagonist exendin(9-39). To elucidate possible cholinergic pathways, we combined exendin(9-39) with the muscarinergic antagonist atropine.
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. GLP-1 also lowers glucagon secretion from pancreatic alpha-cells and delays nutrient delivery from the stomach by inhibiting gastric emptying. These combined effects improve glucose tolerance providing the rationale for a therapeutic potential of GLP-1 analogues in the treatment of diabetes mellitus.
A dominant gastrointestinal action of synthetic GLP-1 is the inhibition of gastroduodenal and stimulation of pyloric motility, resulting in a delay of gastric emptying and in decreased glycemic excursions. Postprandial glucose fluctuations have been demonstrated to be an important determinant of glycemic control as assessed by A1C. Moreover, emerging evidence shows a strong link between transient postprandial hyperglycemia and microvascular and macrovascular complications in diabetes mellitus. Deceleration of gastric emptying is now considered as mechanism to lower postprandial glycemia in patients with diabetes mellitus. It is part of the pharmacodynamic profile of new antidiabetic incretinomimetica. In contrast, inhibition of the enzyme dipeptidylpeptidase 4 (DPP-4) which is responsible for the rapid degradation of GLP-1 failed to show an effect on gastric emptying in human although plasma GLP-1 was increased by twofold. Most of our understanding of the effects of GLP-1 is based upon studies employing synthetic GLP-1 whereas only little is known about endogenously released GLP-1.
Using the specific GLP-1 receptor antagonist exendin(9-39) we were able to show that endogenous GLP-1 acts as an incretin hormone in human. Moreover, the inhibition of antroduodenal and the stimulation of pyloric motility during a duodenal glucose load were reversed by the GLP-1 receptor antagonist. In order to more completely evaluate the effects of GLP-1 as an enterogastrone, the present study examines the effects of exendin(9-39) on antropyloroduodenal and proximal gastric motility during a physiological meal. As cholinergic pathways are thought to be involved in inhibitory actions of GLP-1 we combine the GLP-1 receptor antagonist with the muscarinergic antagonist atropine. To ensure a comparable stimulation of GLP-1 under all experimental conditions we decide to perfuse the meal directly into the duodenum.
Comparisons: In ten healthy volunteers, an interdigestive period is followed by 70 min with duodenal perfusion of a mixed liquid meal (250 kcal). On four days and in random order, exendin(9-39) (300 pmol•kg-1•min-1), atropine (5 µg•kg-1•h-1), exendin(9-39) + atropine or saline are intravenously infused. Antro-pyloro-duodenal perfusion manometry and fundic motility (electronic barostat) are assessed in parallel. Isobaric distensions of the proximal stomach were performed determining compliance.
- Conditions
- Digestive Physiology, Gastrointestinal Motility, Gastrointestinal Hormones, Glucagon-like Peptide 1, Exendin (9-39)
- Being tested
- exendin(9-39)amide, atropine
- Keywords
- GLP-1, exendin(9-39), atropine, human, motility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
exendin(9-39)amideDrug
atropineDrug
| Study group | Role | What they receive |
|---|---|---|
| saline-saline | Placebo comparator | saline IV + saline IV |
| saline-exendin(9-39)amide | Active comparator | saline IV
+ exendin(9-39)amide IV Receives: Drug: exendin(9-39)amide |
| saline-atropine | Active comparator | saline IV
+ atropine IV Receives: Drug: atropine |
| exendin(9-39)amide-atropine | Active comparator | exendin(9-39)amide IV
+ atropine IV Receives: Drug: exendin(9-39)amide; Drug: atropine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of exendin(9-39) on gastroduodenal motility Effect of exendin(9-39) on gastroduodenal motility with simultaneous atropine
Measured: within the 200 min study period
Secondary outcomes (1)
Effect of exendin(9-39) on blood glucose levels and plasma immunoreactivities of insulin, glucagon, and pancreatic polypeptide
Measured: within the 200 min study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2007 (estimated)
- Study startFeb 1999
- Study completionSep 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Digestive PhysiologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Double blind
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation, Philipps University Marburg
- Investigators
- Joerg Schirra, MD, Principal investigator, Clinical Research Unit, Dept. of Internal Medicine II, University of Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00468091
- Sponsor's protocol ID
- MATEX
- Other IDs
- DFG Ar149/1-2, DFG 527/5-2
- Status last verified
- Apr 2007
- First submitted
- 30 Apr 2007
- Last updated
- 1 Apr 2015
- Results posted
- 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 9525985Schirra J, Houck P, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 2000 May;46(5):622-31. doi: 10.1136/gut.46.5.622.
PubMed 10764704Schirra J, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on motility and sensation of the proximal stomach in humans. Gut. 2002 Mar;50(3):341-8. doi: 10.1136/gut.50.3.341.
PubMed 11839712Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, Goke B. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006 Feb;55(2):243-51. doi: 10.1136/gut.2004.059741. Epub 2005 Jun 28.
PubMed 15985560
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Antro-pyloro-duodenal and Proximal Gastric Motility by GLP-1: Involvement of Cholinergic Pathways
- ClinicalTrials.gov ID
- NCT00468091
- Acronym / sponsor ID
- MATEX
- Conditions
- Digestive Physiology, Gastrointestinal Motility, Gastrointestinal Hormones, Glucagon-like Peptide 1, Exendin (9-39)
- Keywords
- GLP-1, exendin(9-39), atropine, human, motility
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Collaborators
- German Research Foundation, Philipps University Marburg
- Study start
- Feb 1999
- Study completion
- Sep 2000 (actual)
- First posted
- 1 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study in humans is to define the effects of the endogenous hormone GLP-1 on gastroduodenal motility and on endocrine pancreatic secretion by using the specific GLP-1 receptor antagonist exendin(9-39). To elucidate possible cholinergic pathways, we combined exendin(9-39) with the muscarinergic antagonist atropine.
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. GLP-1 also lowers glucagon secretion from pancreatic alpha-cells and delays nutrient delivery from the stomach by inhibiting gastric emptying. These combined effects improve glucose tolerance providing the rationale for a therapeutic potential of GLP-1 analogues in the treatment of diabetes mellitus.
A dominant gastrointestinal action of synthetic GLP-1 is the inhibition of gastroduodenal and stimulation of pyloric motility, resulting in a delay of gastric emptying and in decreased glycemic excursions. Postprandial glucose fluctuations have been demonstrated to be an important determinant of glycemic control as assessed by A1C. Moreover, emerging evidence shows a strong link between transient postprandial hyperglycemia and microvascular and macrovascular complications in diabetes mellitus. Deceleration of gastric emptying is now considered as mechanism to lower postprandial glycemia in patients with diabetes mellitus. It is part of the pharmacodynamic profile of new antidiabetic incretinomimetica. In contrast, inhibition of the enzyme dipeptidylpeptidase 4 (DPP-4) which is responsible for the rapid degradation of GLP-1 failed to show an effect on gastric emptying in human although plasma GLP-1 was increased by twofold. Most of our understanding of the effects of GLP-1 is based upon studies employing synthetic GLP-1 whereas only little is known about endogenously released GLP-1.
Using the specific GLP-1 receptor antagonist exendin(9-39) we were able to show that endogenous GLP-1 acts as an incretin hormone in human. Moreover, the inhibition of antroduodenal and the stimulation of pyloric motility during a duodenal glucose load were reversed by the GLP-1 receptor antagonist. In order to more completely evaluate the effects of GLP-1 as an enterogastrone, the present study examines the effects of exendin(9-39) on antropyloroduodenal and proximal gastric motility during a physiological meal. As cholinergic pathways are thought to be involved in inhibitory actions of GLP-1 we combine the GLP-1 receptor antagonist with the muscarinergic antagonist atropine. To ensure a comparable stimulation of GLP-1 under all experimental conditions we decide to perfuse the meal directly into the duodenum.
Comparisons: In ten healthy volunteers, an interdigestive period is followed by 70 min with duodenal perfusion of a mixed liquid meal (250 kcal). On four days and in random order, exendin(9-39) (300 pmol•kg-1•min-1), atropine (5 µg•kg-1•h-1), exendin(9-39) + atropine or saline are intravenously infused. Antro-pyloro-duodenal perfusion manometry and fundic motility (electronic barostat) are assessed in parallel. Isobaric distensions of the proximal stomach were performed determining compliance.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| saline-saline | Placebo comparator | –saline IV + saline IV |
| saline-exendin(9-39)amide | Active comparator | Drug: exendin(9-39)amidesaline IV + exendin(9-39)amide IV |
| saline-atropine | Active comparator | Drug: atropinesaline IV + atropine IV |
| exendin(9-39)amide-atropine | Active comparator | Drug: exendin(9-39)amide, Drug: atropineexendin(9-39)amide IV + atropine IV |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female (postmenopausal, surgically sterile or using double-barrier method of contraception) healthy volunteers
- Age 18-65 years
- 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
Key exclusion criteria (12 listed)
- Diabetes mellitus
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| exendin(9-39)amide | Drug | exendin(9-39)amide-atropine, saline-exendin(9-39)amide |
| atropine | Drug | exendin(9-39)amide-atropine, saline-atropine |
Primary outcome
Effect of exendin(9-39) on gastroduodenal motility Effect of exendin(9-39) on gastroduodenal motility with simultaneous atropine
Time frame: within the 200 min study period
1 secondary outcome
Effect of exendin(9-39) on blood glucose levels and plasma immunoreactivities of insulin, glucagon, and pancreatic polypeptide
Time frame: within the 200 min study period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2015.
- Background: PubMed 9525985Schirra 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.
- Background: PubMed 10764704Schirra J, Houck P, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 2000 May;46(5):622-31. doi: 10.1136/gut.46.5.622.
- Background: PubMed 11839712Schirra J, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on motility and sensation of the proximal stomach in humans. Gut. 2002 Mar;50(3):341-8. doi: 10.1136/gut.50.3.341.
- Background: PubMed 15985560Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, Goke B. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006 Feb;55(2):243-51. doi: 10.1136/gut.2004.059741. Epub 2005 Jun 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joerg Schirra, MD principal investigator
Clinical Research Unit, Dept. of Internal Medicine II, University of Munich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing exendin(9-39)amide and atropine in people with Digestive Physiology and Gastrointestinal Motility, 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 6 inclusion and 12 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 1 Apr 2015. 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. Some participants in this study may receive a placebo. 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?
Effect of exendin(9-39) on gastroduodenal motility Effect of exendin(9-39) on gastroduodenal motility with simultaneous atropine (time frame: within the 200 min 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 NCT00468091, which also lists 4 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 1 Apr 2015.