HealthyPhase 3NCT04466618
Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes
A Phase 3 study testing Saline, Exendin-9,39 and Saline + Intralipid/Heparin in people with Healthy and Type 2 Diabetes, run by Adrian Vella at 1 site in United States.
Trial summary
GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Type 2 Diabetes
- What is being tested?
- Saline, Exendin-9,39 and Saline + Intralipid/Heparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2021to 31 Dec 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Weight-stable, non-diabetic subjects
- Weight-stable, diabetic subjects treated with diet and lifestyle alone or with metformin monotherapy
Who cannot join
- Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- HbA1c ≥ 6.5%
- Use of glucose-lowering agents.
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Active systemic illness or malignancy.
Show all 15Show fewer
- Symptomatic macrovascular or microvascular disease.
- Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- Use of any glucose-lowering agent other than metformin.
- 2 or more fasting glucose values > 250mg/dl on medication or after medication withdrawal.
- Unwillingness or inability to withdraw medication for three weeks prior to, and for the duration of the study.
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Active systemic illness or malignancy.
- Symptomatic macrovascular or microvascular disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: To Determine the Effect of Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes
GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.
Read the detailed description
Accumulating evidence suggests that in rodents and humans GLP-1 is synthesized within islets and may act locally in a paracrine fashion. Indeed, mice with genetic loss of intra-islet GLP-1 exhibit decreased insulin secretion and impaired response to metabolic stressors. 'Pancreatic' GLP-1 may contribute to the effects of DPP-4 inhibitors in rodents and humans. Antagonism of GLP1R with exendin-9,39 during fasting impairs the islet cell response to an I.V. glucose challenge. Islet GLP-1 content is increased in T2DM and in islets from non-diabetic humans exposed to hyperglycemia and Free Fatty Acids. These observations imply that paracrine GLP-1 secretion supports islet function in the presence of glucolipotoxicity. In this experiment we will examine the role of endogenous GLP-1 secretion in people with and without T2DM and during β-cell stress induced by FFA elevation.
- Conditions
- Healthy, Type 2 Diabetes
- Being tested
- Saline, Exendin-9,39, Saline + Intralipid/Heparin, Exendin-9,39 + Intralipid/Heparin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineBiological
Saline infused during the study
Exendin-9,39Biological
Exendin-9,39 infused during the study
Saline + Intralipid/HeparinBiological
Saline infused during acute insulin resistance
Exendin-9,39 + Intralipid/HeparinBiological
Exendin-9,39 infused during acute insulin resistance
| Study group | Role | What they receive |
|---|---|---|
| Saline | Placebo comparator | Saline infusion Receives: Biological: Saline |
| Exendin-9,39 | Active comparator | Exendin-9,39 infusion Receives: Biological: Exendin-9,39 |
| Saline + Intralipid/Heparin | Active comparator | Induction of acute insulin resistance during Saline infusion Receives: Biological: Saline + Intralipid/Heparin |
| Exendin-9,39 + Intralipid/Heparin | Active comparator | Induction of acute insulin resistance during Exendin-9,39 infusion Receives: Biological: Exendin-9,39 + Intralipid/Heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39
Concentrations of glucagon Measured by immunoassay over the -30 to 0 minutes of study.
On one study day subjects received saline, on the other exendin-9,39. The infusion commenced at -120 minutes.
Measured: Average concentration over the -30 to 0 minutes of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2020
- Study start15 Apr 2021
- Primary completion15 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adrian Vella
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Adrian Vella, Mayo Clinic
- Investigators
- Adrian Vella, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04466618
- Sponsor's protocol ID
- 20-003993
- Other IDs
- R01DK126206
- Status last verified
- Dec 2023
- First submitted
- 30 Jun 2020
- Last updated
- 26 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Welch AA, Farahani RA, Egan AM, Laurenti MC, Zeini M, Vella M, Bailey KR, Cobelli C, Dalla Man C, Matveyenko A, Vella A. Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans. J Clin Invest. 2023 Nov 15;133(22):e173495. doi: 10.1172/JCI173495.
PubMed 37751301
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Determine the Effect of Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT04466618
- Acronym / sponsor ID
- 20-003993
- Conditions
- Healthy, Type 2 Diabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Adrian VellaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 15 Apr 2021 (actual)
- Primary completion
- 15 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 10 Jul 2020 (actual)
- Results
- Posted 26 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.
Detailed description
Accumulating evidence suggests that in rodents and humans GLP-1 is synthesized within islets and may act locally in a paracrine fashion. Indeed, mice with genetic loss of intra-islet GLP-1 exhibit decreased insulin secretion and impaired response to metabolic stressors. 'Pancreatic' GLP-1 may contribute to the effects of DPP-4 inhibitors in rodents and humans. Antagonism of GLP1R with exendin-9,39 during fasting impairs the islet cell response to an I.V. glucose challenge. Islet GLP-1 content is increased in T2DM and in islets from non-diabetic humans exposed to hyperglycemia and Free Fatty Acids. These observations imply that paracrine GLP-1 secretion supports islet function in the presence of glucolipotoxicity. In this experiment we will examine the role of endogenous GLP-1 secretion in people with and without T2DM and during β-cell stress induced by FFA elevation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Saline | Placebo comparator | Biological: SalineSaline infusion |
| Exendin-9,39 | Active comparator | Biological: Exendin-9,39Exendin-9,39 infusion |
| Saline + Intralipid/Heparin | Active comparator | Biological: Saline + Intralipid/HeparinInduction of acute insulin resistance during Saline infusion |
| Exendin-9,39 + Intralipid/Heparin | Active comparator | Biological: Exendin-9,39 + Intralipid/HeparinInduction of acute insulin resistance during Exendin-9,39 infusion |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Weight-stable, non-diabetic subjects
- Weight-stable, diabetic subjects treated with diet and lifestyle alone or with metformin monotherapy
Key exclusion criteria (15 listed)
- Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
- HbA1c ≥ 6.5%
- Use of glucose-lowering agents.
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
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 |
|---|---|---|
| SalineSaline infused during the study | Biological | Saline |
| Exendin-9,39Exendin-9,39 infused during the study | Biological | Exendin-9,39 |
| Saline + Intralipid/HeparinSaline infused during acute insulin resistance | Biological | Saline + Intralipid/Heparin |
| Exendin-9,39 + Intralipid/HeparinExendin-9,39 infused during acute insulin resistance | Biological | Exendin-9,39 + Intralipid/Heparin |
Primary outcome
Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39
Time frame: Average concentration over the -30 to 0 minutes of study
Concentrations of glucagon Measured by immunoassay over the -30 to 0 minutes of study. On one study day subjects received saline, on the other exendin-9,39. The infusion commenced at -120 minutes.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37751301Welch AA, Farahani RA, Egan AM, Laurenti MC, Zeini M, Vella M, Bailey KR, Cobelli C, Dalla Man C, Matveyenko A, Vella A. Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans. J Clin Invest. 2023 Nov 15;133(22):e173495. doi: 10.1172/JCI173495.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Healthy
Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers
RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Active, not recruitingPhase 1
A Study to Learn How Different Amounts of the Study Medicine Called PF-07985631 Are Tolerated and Act in the Body of Healthy Adults
Healthy
Not yet recruitingObservational study
Collection and Distribution of Blood Components From Healthy Donors for In Vitro Research Use
Blood Donors, Apheresis
Recruiting
Metabolic Impact of VLCPUFA-Rich Fish Oil: A Clinical Study on Omega-3 Index Enhancement in Healthy Individuals
Fatty Acids, Omega-3, Fish Oils
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.
Adrian Vella principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Saline, Exendin-9,39 and Saline + Intralipid/Heparin in people with Healthy and Type 2 Diabetes, run by Adrian Vella 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 2 inclusion and 15 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 26 Dec 2023. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39 (time frame: Average concentration over the -30 to 0 minutes of study). 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 NCT04466618, which also lists 1 linked publication.
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 Dec 2023.