Insulin SecretionPhase 1NCT02550548
Incretin Action in Physiology and Diabetes
A Phase 1 study testing GIP infusion, GLP-1 infusion and Ex-9 infusion in people with Insulin Secretion, run by David D'Alessio, M.D. at 1 site in United States.
Trial summary
This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Secretion
- What is being tested?
- GIP infusion, GLP-1 infusion and Ex-9 infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2016to 16 Apr 2021
- 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
- healthy adult volunteers
- fasting plasma glucose value ≤ 95 mg/dL, measured at screening visit
- HbA1c ≤ 5.9%, measured at screening visit
Who cannot join
- history of diabetes diagnosis, including gestational diabetes
- presence of Type II diabetes mellitus among any first degree family members
- rheumatoid arthritis
- inflammatory bowel disease
- unstable angina or uncompensated heart failure
- pulmonary disorders including COPD and asthma
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- malabsorptive GI disease, such as celiac disease, or gastric bypass
- significant hepatic disease
- renal insufficiency (eGFR < 60 mL/kg/min)
- anemia (hematocrit < 34%) as measured at screening visit
- pregnancy
- uncontrolled hypertension
- consumption of daily medications that alter glucose metabolism or GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Center for Living
Durham, North Carolina, 27705
About this study
This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. However, there are important gaps in understanding incretin function that limit application of this system; this project will address several of these. A secondary, but critical aspect of this research is focus on inter-individual variation in the physiology of the incretin system. This is a novel direction for research in this field and is critical to advancing the concept of individualized medical care in diabetes by establishing whether there is a physiologic basis for predicting the existence of responders and non-responders to incretin therapies.
Currently, we have described only Aim 1 from this grant in this protocol registration. While Aim 2 and 3 are described in the grant, Aim 1 will be conducted first and the results from this Aim and / or the publication of other results in the field may affect the approach to Aims 2 and 3.
- Conditions
- Insulin Secretion
- Being tested
- GIP infusion, GLP-1 infusion, Ex-9 infusion
- Keywords
- Incretins, GLP-1, GIP, hyperglycemic clamp, Glucagon
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GIP infusionDrug
after establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused
GLP-1 infusionDrug
after establishing a hyperglycemic clamp (target: 125 mg/dL) GLP-1 will be infused
Ex-9 infusionDrug
Ex-9 infusion will be initiated at start of hyperglycemic clamp (target: 125 mg/dL)
| Study group | Role | What they receive |
|---|---|---|
| GIP infusion | Experimental | During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP infused at 4 incremental dosages, (initial dose will be 2.0 ng/kg/min, followed by 4.0, 8.0, and 16.0 ng/kg/min). Each dose will be infused continuously for 30 minutes, followed immediately by the next higher dose. The total time of this procedure is 240 minutes. Receives: Drug: GIP infusion |
| GLP-1 infusion | Experimental | During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GLP-1 infused at 4 incremental dosages, (initial dose will be 1.0 ng/kg/min, followed by 2.0, 3.0, and 4.0 ng/kg/min). Each dose will be infused continuously for 30 minutes, followed immediately by the next higher dose. The total time of this procedure is 240 minutes. Receives: Drug: GLP-1 infusion |
| GIP + GLP-1 infusion | Experimental | During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP + GLP-1 infused simultaneously at 4 incremental dosages (doses will be half the amounts described above). These doses will be infused continuously for 30 minutes, followed immediately by the next higher doses. The total time of this procedure is 240 minutes. Receives: Drug: GIP infusion; Drug: GLP-1 infusion |
| GIP + Ex-9 infusion | Experimental | During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP infused at 4 incremental dosages (as described above) with Ex-9 infused at a steady dose of 2.5 mcg/kg/min starting 90 minutes before the GIP infusion and maintained throughout the clamp experiment. The total time of this procedure is 240 minutes. Receives: Drug: GIP infusion; Drug: Ex-9 infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beta cell sensitivity
Beta-cell sensitivity for each incretin will equal the slope of the insulin secretion rate divided by the specific incretin level (GLP-1 or GIP)
Measured: 30 minute infusion periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study start21 Apr 2016
- Primary completion16 Apr 2021
- Study completion16 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin SecretionStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- David D'Alessio, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David D'Alessio, M.D., Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02550548
- Sponsor's protocol ID
- Pro00065698
- Other IDs
- R01DK101991
- Status last verified
- Nov 2023
- First submitted
- 3 Sep 2015
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incretin Action in Physiology and Diabetes
- ClinicalTrials.gov ID
- NCT02550548
- Acronym / sponsor ID
- Pro00065698
- Conditions
- Insulin Secretion
- Keywords
- Incretins, GLP-1, GIP, hyperglycemic clamp, Glucagon
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- David D'Alessio, M.D.University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 21 Apr 2016 (actual)
- Primary completion
- 16 Apr 2021 (actual)
- Study completion
- 16 Apr 2021 (actual)
- First posted
- 15 Sep 2015 (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.
This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. However, there are important gaps in understanding incretin function that limit application of this system; this project will address several of these. A secondary, but critical aspect of this research is focus on inter-individual variation in the physiology of the incretin system. This is a novel direction for research in this field and is critical to advancing the concept of individualized medical care in diabetes by establishing whether there is a physiologic basis for predicting the existence of responders and non-responders to incretin therapies.
Currently, we have described only Aim 1 from this grant in this protocol registration. While Aim 2 and 3 are described in the grant, Aim 1 will be conducted first and the results from this Aim and / or the publication of other results in the field may affect the approach to Aims 2 and 3.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GIP infusion | Experimental | Drug: GIP infusionDuring a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP infused at 4 incremental dosages, (initial dose will be 2.0 ng/kg/min, followed by 4.0, 8.0, and 16.0 ng/kg/min). Each dose will be infused continuously for 30 minutes, followed immediately by the next higher dose. The total time of this procedure is 240 minutes. |
| GLP-1 infusion | Experimental | Drug: GLP-1 infusionDuring a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GLP-1 infused at 4 incremental dosages, (initial dose will be 1.0 ng/kg/min, followed by 2.0, 3.0, and 4.0 ng/kg/min). Each dose will be infused continuously for 30 minutes, followed immediately by the next higher dose. The total time of this procedure is 240 minutes. |
| GIP + GLP-1 infusion | Experimental | Drug: GIP infusion, Drug: GLP-1 infusionDuring a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP + GLP-1 infused simultaneously at 4 incremental dosages (doses will be half the amounts described above). These doses will be infused continuously for 30 minutes, followed immediately by the next higher doses. The total time of this procedure is 240 minutes. |
| GIP + Ex-9 infusion | Experimental | Drug: GIP infusion, Drug: Ex-9 infusionDuring a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP infused at 4 incremental dosages (as described above) with Ex-9 infused at a steady dose of 2.5 mcg/kg/min starting 90 minutes before the GIP infusion and maintained throughout the clamp experiment. The total time of this procedure is 240 minutes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- healthy adult volunteers
- fasting plasma glucose value ≤ 95 mg/dL, measured at screening visit
- HbA1c ≤ 5.9%, measured at screening visit
Key exclusion criteria (13 listed)
- history of diabetes diagnosis, including gestational diabetes
- presence of Type II diabetes mellitus among any first degree family members
- rheumatoid arthritis
- inflammatory bowel disease
- unstable angina or uncompensated heart failure
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 |
|---|---|---|
| GIP infusionafter establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused | Drug | GIP + Ex-9 infusion, GIP + GLP-1 infusion, GIP infusion |
| GLP-1 infusionafter establishing a hyperglycemic clamp (target: 125 mg/dL) GLP-1 will be infused | Drug | GIP + GLP-1 infusion, GLP-1 infusion |
| Ex-9 infusionEx-9 infusion will be initiated at start of hyperglycemic clamp (target: 125 mg/dL) | Drug | GIP + Ex-9 infusion |
Primary outcome
Beta cell sensitivity
Time frame: 30 minute infusion periods
Beta-cell sensitivity for each incretin will equal the slope of the insulin secretion rate divided by the specific incretin level (GLP-1 or GIP)
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 18 Nov 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 GIP infusion, GLP-1 infusion and Ex-9 infusion in people with Insulin Secretion, run by David D'Alessio, M.D. 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 3 inclusion and 13 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 18 Nov 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. 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?
Beta cell sensitivity (time frame: 30 minute infusion periods). 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 18 Nov 2023.