Does the Vagus Nerve Mediate the Effects of Xenin-25Phase 1NCT01951716
Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy
A Phase 1 study testing Graded Glucose Infusion with GIP Alone, Graded Glucose Infusion with xenin-25 alone and Graded Glucose Infusion with GIP plus xenin-25 in people with Does the Vagus Nerve Mediate the Effects of Xenin-25, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Glucose-dependent Insulinotropic Polypeptide (GIP) and xenin-25 are peptide hormones produced/released from your intestines and help regulate blood sugar levels after you eat. We have previously performed studies in humans that measured the effects of xenin-25 and GIP (alone and together) on blood sugar levels. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Does the Vagus Nerve Mediate the Effects of Xenin-25
- What is being tested?
- Graded Glucose Infusion with GIP Alone, Graded Glucose Infusion with xenin-25 alone and Graded Glucose Infusion with GIP plus xenin-25
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Jul 2018
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ages 18-70. No minors will be studied.
- Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).
- Healthy volunteers with no clinical evidence of Type 2 Diabetes
- Healthy volunteers who have undergone a complete truncal vagotomy
- Healthy volunteers who have not had a complete truncal vagotomy
- Women of childbearing potential must be currently taking/using a method of birth control that is acceptable to the investigators. A pregnancy test will be done at the beginning of each visit. Any woman with a positive pregnancy test will be removed from the study.
- Willingness to complete all required visits
Who cannot join
- <18years of age or >70 years of age
- Lacks cognitive ability to sign the consent \&/or follow the study directions for themselves
- Women unwilling to comply with using an acceptable method of contraception during the course of the study, or who are currently breast-feeding.
- Volunteers with Type 2 diabetes
- Volunteers with a history of Acute Pancreatitis
- Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia (triglycerides >400mg/ml) hypercalcemia (blood calcium level >11.md/dl) and/or the presence of gallstones.
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- Volunteers with a history of gastrointestinal disorders, particularly related to gastric motility/emptying such as gastric bypass, documented gastro-paresis in diabetic volunteers.
- Volunteers with a history of cancer. Exception: skin cancer.
- Known heart, kidney. liver or pancreatic disease requiring medications.
- Subjects unwilling to allow the use of their own blood or the human albumin in the preparation of the peptides.
- Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Glucose-dependent Insulinotropic Polypeptide (GIP) and xenin-25 are peptide hormones produced/released from your intestines and help regulate blood sugar levels after you eat. We have previously performed studies in humans that measured the effects of xenin-25 and GIP (alone and together) on blood sugar levels. One study was conducted with an intravenous infusion of glucose but without ingestion of a meal. In this study, xenin-25 increased the effects of GIP on insulin secretion- but only in humans without type 2 diabetes mellitus (T2DM). A second study was conducted in conjunction with ingestion of a meal. In this study, xenin-25 reduced blood glucose levels by delaying gastric emptying and this effect was similar in humans with and without T2DM. A variety of studies that we have performed suggest that xenin-25 works by activating nerves. A specific nerve called the vagus nerve plays an important role in regulating insulin secretion. This study will determine if the vagus nerve (which was disrupted if you had a vagotomy) is needed for the effects of xenin-25 on insulin secretion and/or gastric emptying.
Read the detailed description
Two groups of subjects, both without T2DM, will be studied. One group will consist of people who previously received a complete truncal vagotomy as part of a surgical treatment unrelated to this research project. The other group will be subjects who have not had a truncal vagotomy.
Initially, each potential participant will be administered an oral glucose tolerance test at the screening visit to make sure that they do not have type 2 diabetes. They will also have a sham feeding test to check for the completeness (or absence) of the vagotomy. As outlined below, each subject will then receive 4 graded glucose infusions (GGI) and 2 meal tolerance tests (MTT)- each on a separate occasion following an overnight fast.
For each GGI, the subject will be given an intravenous infusion of glucose such that blood glucose levels slowly increase over a 4 hour period. On separate occasions, the participant will also receive a primed-continuous infusion of GIP alone, xenin-25 alone, GIP plus xenin-25, or placebo (constant dose of 4 pmoles x kg-1 x min-1). Blood samples will be collected before and during the GGI for the measurement of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of GIP, xenin-25, or the combination of GIP plus xenin-25 on insulin secretion in humans and thus, if this signaling circuit is impaired in humans with T2DM.
For the MTTs, the participant will ingest a liquid meal (Boost Plus) plus acetaminophen (Tylenol). On separate occasions, a primed-continuous infusion of vehicle alone or xenin-25 alone (constant dose of 12 pmoles x kg-1 x min-1) will be initiated at the same time the meal is ingested. Blood samples will be collected before and during the MTT for the measurement of acetaminophen, glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. The rate of acetaminophen appearance in the blood is an indirect measure of the rate of gastric emptying. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of xenin-25 on gastric emptying in humans.
- Being tested
- Graded Glucose Infusion with Placebo, Graded Glucose Infusion with GIP Alone, Graded Glucose Infusion with xenin-25 alone, Graded Glucose Infusion with GIP plus xenin-25, Meal Tolerance Test with Placebo
- Keywords
- Vagotomy, Vagus Nerve, Xenin-25, GIP, Insulin Secretion, Glucagon Secretion, Gastric Emptying
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Graded Glucose Infusion with PlaceboDrug
Also called GGI with Albumin Alone
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes.
Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 240 minutes.
The study is finished at 240 minutes.
Graded Glucose Infusion with GIP AloneDrug
Also called GGI with GIP
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes.
Starting at 0 minutes, a primed-continuous intravenous infusion of GIP in saline containing 1% human albumin will continue for 240 minutes.
The study is finished at 240 minutes.
Graded Glucose Infusion with xenin-25 aloneDrug
Also called GGI with Xenin
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes.
Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 240 minutes.
The study is finished at 240 minutes.
Graded Glucose Infusion with GIP plus xenin-25Drug
Also called GGI with GIP plus Xenin
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes.
Starting at 0 minutes, a primed-continuous intravenous infusion of GIP plus xenin-25 in saline containing 1% human albumin will continue for 240 minutes.
The study is finished at 240 minutes.
Meal Tolerance Test with PlaceboDrug
Also called MTT with Albumin Alone
At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested.
Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 300 minutes.
The study is finished at 300 minutes.
Meal Tolerance Test with xenin-25Drug
Also called MTT with xenin
At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested.
Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 300 minutes.
The study is finished at 300 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Truncal Vagotomy | Experimental | Healthy participants without diabetes who have undergone a complete truncal vagotomy Receives: Drug: Graded Glucose Infusion with Placebo; Drug: Graded Glucose Infusion with GIP Alone; Drug: Graded Glucose Infusion with xenin-25 alone; Drug: Graded Glucose Infusion with GIP plus xenin-25; Drug: Meal Tolerance Test with Placebo; Drug: Meal Tolerance Test with xenin-25 |
| No Vagotomy | Experimental | Healthy participants without diabetes who have not had a complete truncal vagotomy Receives: Drug: Graded Glucose Infusion with Placebo; Drug: Graded Glucose Infusion with GIP Alone; Drug: Graded Glucose Infusion with xenin-25 alone; Drug: Graded Glucose Infusion with GIP plus xenin-25; Drug: Meal Tolerance Test with Placebo; Drug: Meal Tolerance Test with xenin-25 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin secretion rates will be measured during the GGI and MTTs
Measured: 3 years
Secondary outcomes (1)
Plasma acetaminophen levels will be measured during MTTs
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2013 (estimated)
- Study startJan 2013
- Primary completionJul 2018 (estimated)
- Study completionJul 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Does the Vagus Nerve Mediate the Effects of Xenin-25Studies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Sponsor
- Investigators
- Burton M Wice, PhD, Principal investigator, Washington University School of MedicineDominic Reeds, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01951716
- Sponsor's protocol ID
- 08-0861 D
- Status last verified
- Apr 2018
- First submitted
- 23 Sep 2013
- Last updated
- 26 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy
- ClinicalTrials.gov ID
- NCT01951716
- Acronym / sponsor ID
- 08-0861 D
- Keywords
- Vagotomy, Vagus Nerve, Xenin-25, GIP, Insulin Secretion, Glucagon Secretion, Gastric Emptying
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- American Diabetes Association
- Study start
- Jan 2013
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Jul 2018 (estimated)
- First posted
- 27 Sep 2013 (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.
Glucose-dependent Insulinotropic Polypeptide (GIP) and xenin-25 are peptide hormones produced/released from your intestines and help regulate blood sugar levels after you eat. We have previously performed studies in humans that measured the effects of xenin-25 and GIP (alone and together) on blood sugar levels. One study was conducted with an intravenous infusion of glucose but without ingestion of a meal. In this study, xenin-25 increased the effects of GIP on insulin secretion- but only in humans without type 2 diabetes mellitus (T2DM). A second study was conducted in conjunction with ingestion of a meal. In this study, xenin-25 reduced blood glucose levels by delaying gastric emptying and this effect was similar in humans with and without T2DM. A variety of studies that we have performed suggest that xenin-25 works by activating nerves. A specific nerve called the vagus nerve plays an important role in regulating insulin secretion. This study will determine if the vagus nerve (which was disrupted if you had a vagotomy) is needed for the effects of xenin-25 on insulin secretion and/or gastric emptying.
Detailed description
Two groups of subjects, both without T2DM, will be studied. One group will consist of people who previously received a complete truncal vagotomy as part of a surgical treatment unrelated to this research project. The other group will be subjects who have not had a truncal vagotomy.
Initially, each potential participant will be administered an oral glucose tolerance test at the screening visit to make sure that they do not have type 2 diabetes. They will also have a sham feeding test to check for the completeness (or absence) of the vagotomy. As outlined below, each subject will then receive 4 graded glucose infusions (GGI) and 2 meal tolerance tests (MTT)- each on a separate occasion following an overnight fast.
For each GGI, the subject will be given an intravenous infusion of glucose such that blood glucose levels slowly increase over a 4 hour period. On separate occasions, the participant will also receive a primed-continuous infusion of GIP alone, xenin-25 alone, GIP plus xenin-25, or placebo (constant dose of 4 pmoles x kg-1 x min-1). Blood samples will be collected before and during the GGI for the measurement of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of GIP, xenin-25, or the combination of GIP plus xenin-25 on insulin secretion in humans and thus, if this signaling circuit is impaired in humans with T2DM.
For the MTTs, the participant will ingest a liquid meal (Boost Plus) plus acetaminophen (Tylenol). On separate occasions, a primed-continuous infusion of vehicle alone or xenin-25 alone (constant dose of 12 pmoles x kg-1 x min-1) will be initiated at the same time the meal is ingested. Blood samples will be collected before and during the MTT for the measurement of acetaminophen, glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels. Insulin secretion rates will also be calculated. The rate of acetaminophen appearance in the blood is an indirect measure of the rate of gastric emptying. By comparing results for the two groups, we will learn if the vagus nerve mediates the effects of xenin-25 on gastric emptying in humans.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Truncal Vagotomy | Experimental | Drug: Graded Glucose Infusion with Placebo, Drug: Graded Glucose Infusion with GIP Alone, Drug: Graded Glucose Infusion with xenin-25 alone, Drug: Graded Glucose Infusion with GIP plus xenin-25, Drug: Meal Tolerance Test with Placebo, Drug: Meal Tolerance Test with xenin-25Healthy participants without diabetes who have undergone a complete truncal vagotomy |
| No Vagotomy | Experimental | Drug: Graded Glucose Infusion with Placebo, Drug: Graded Glucose Infusion with GIP Alone, Drug: Graded Glucose Infusion with xenin-25 alone, Drug: Graded Glucose Infusion with GIP plus xenin-25, Drug: Meal Tolerance Test with Placebo, Drug: Meal Tolerance Test with xenin-25Healthy participants without diabetes who have not had a complete truncal vagotomy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ages 18-70. No minors will be studied.
- Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).
- Healthy volunteers with no clinical evidence of Type 2 Diabetes
- Healthy volunteers who have undergone a complete truncal vagotomy
- Healthy volunteers who have not had a complete truncal vagotomy
Key exclusion criteria (11 listed)
- <18years of age or >70 years of age
- Lacks cognitive ability to sign the consent \&/or follow the study directions for themselves
- Women unwilling to comply with using an acceptable method of contraception during the course of the study, or who are currently breast-feeding.
- Volunteers with Type 2 diabetes
- Volunteers with a history of Acute Pancreatitis
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 |
|---|---|---|
| Graded Glucose Infusion with PlaceboAlso: GGI with Albumin AloneStarting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. | Drug | No Vagotomy, Truncal Vagotomy |
| Graded Glucose Infusion with GIP AloneAlso: GGI with GIPStarting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. | Drug | No Vagotomy, Truncal Vagotomy |
| Graded Glucose Infusion with xenin-25 aloneAlso: GGI with XeninStarting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. | Drug | No Vagotomy, Truncal Vagotomy |
| Graded Glucose Infusion with GIP plus xenin-25Also: GGI with GIP plus XeninStarting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP plus xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes. | Drug | No Vagotomy, Truncal Vagotomy |
| Meal Tolerance Test with PlaceboAlso: MTT with Albumin AloneAt 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes. | Drug | No Vagotomy, Truncal Vagotomy |
| Meal Tolerance Test with xenin-25Also: MTT with xeninAt 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes. | Drug | No Vagotomy, Truncal Vagotomy |
Primary outcome
Insulin secretion rates will be measured during the GGI and MTTs
Time frame: 3 years
1 secondary outcome
Plasma acetaminophen levels will be measured during MTTs
Time frame: 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2018.
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.
Burton M Wice, PhD principal investigator
Washington University School of Medicine
Dominic Reeds, MD principal investigator
Washington University School of Medicine
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 Graded Glucose Infusion with GIP Alone, Graded Glucose Infusion with xenin-25 alone and Graded Glucose Infusion with GIP plus xenin-25 in people with Does the Vagus Nerve Mediate the Effects of Xenin-25, run by Washington University School of Medicine at 1 site in United States.
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 11 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: withdrawn, as of the sponsor's last update on 26 Apr 2018. 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 United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
Insulin secretion rates will be measured during the GGI and MTTs (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Apr 2018.