HealthyPhase 3NCT04461015

The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans

A Phase 3 study testing 0.4mU Insulin followed by withdrawal period followed by 0.8mU study and 0.8mU Insulin followed by withdrawal period followed by 0.4mU study in people with Healthy, run by Adrian Vella at 1 site in United States.

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 research is to help understand the relative importance of changes in insulin secretion (which lowers glucose) and changes in glucagon (which raises glucose) to regulate metabolism and the body's ability to make glucose. Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study and 0.8mU Insulin followed by withdrawal period followed by 0.4mU study
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 14 Oct 2020to 6 Jan 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 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

We will recruit 15 otherwise healthy subjects using intramural and local extramural advertising after approval from the Mayo Clinic Institutional Review Board. Individuals who express interest in participating will be invited for a screening visit. Individuals with a BMI < 19 or > 28 kg/m2 will be excluded from the study to avoid potential confounding effects that may result from extreme leanness or from obesity. Subjects will have no known systemic illness, taking any medication that could affect glucose metabolism and no history of upper gastrointestinal surgery.

Who cannot join

Subjects < 18 years of age or > 40 years of age will not be studied to minimize the potential confounding effects of age on glucagon and insulin action. The subjects will not be taking medications that affect glucose metabolism (to be determined by PI) and have no history of chronic illness or upper gastrointestinal surgery. We are seeking to recruit subjects who do not have diabetes (fasting glucose <100mg/dL).

Trial locations and contacts

1 site in 1 country.

United States1 site

Mayo Clinic in Rochester
Rochester, Minnesota, 55905

Other trials in United States

About this study

Read the detailed description

Study A (Insulin 0.4mU/Kg/min): Subjects will be admitted to the CRTU at approximately 1700 on the day prior to study. They will then consume a standard 10kcal/kg meal (55% carbohydrate, 30% fat, 15% protein, caffeine free) and fast overnight. Blood will then be sampled for baseline enrichment and 2H20 (1.67g/kg of body water) will be given in 3 divided doses at 2200, 2400 and 0200. The following morning (approximately 0530), a forearm vein will be cannulated to allow infusions to be performed. In addition, a cannula will be inserted retrogradely into a vein of the contra-lateral dorsum of the hand. This will be placed in a heated Plexiglas box maintained at around 120oF to allow sampling of arterialized venous blood. At approximately 0600 (-180 min), a primed, (10microCi prime, 0.1microCi/min continuous) infusion containing trace amounts of glucose labeled with [3-3H] glucose will be started and continued till 0900 (0 min).

At 0900 (0 min), the infusion will be varied so as to mimic the anticipated pattern of fall of EGP. In addition, glucose also labeled with [3-3H] glucose will be infused so as to maintain glucose concentrations at ~ 95mg/dL. Peripheral venous glucose concentrations will be measured every 10 minutes to allow the infusion rate of glucose to be adjusted as necessary.

Simultaneously, an infusion of somatostatin (60ng/kg/min) will be started at time 0 to inhibit endogenous islet secretion and therefore ensure identical portal insulin concentrations on the two study days. Insulin will be infused at a constant rate known to produce ~ 50% suppression of EGP (0.4mU/Kg/min).

From 0900 (0 min) to 1030 (90 min) no glucagon will be infused. Subsequently, a glucagon infusion will commence (91 - 180 min) at 0.35 ng/Kg/min and then increase to 0.70 ng/Kg/min (181- 270 min), a rate which will be maintained till the end of the study (1330).

Study B (0.8mU/Kg/min): Approximately 1-2 weeks after the first study visit, subjects will be asked to return to the CRTU. This study visit will be similar to Study A. However, insulin will be infused at 0.8mU/Kg/min 0 to 270 minutes.

Conditions: Healthy
Being tested: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study, 0.8mU Insulin followed by withdrawal period followed by 0.4mU study

What participants receive

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

0.4mU Insulin followed by withdrawal period followed by 0.8mU studyDrug
Also called 0.4 then 0.8
Clamp study with insulin infused at 0.4 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.8 mU/Kg/min
0.8mU Insulin followed by withdrawal period followed by 0.4mU studyDrug
Also called 0.8 then 0.4
Clamp study with insulin infused at 0.8 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.4 mU/Kg/min

Study groups in NCT04461015
Study group	Role	What they receive
0.4mU Insulin	Other	During the euglycemic clamp insulin will be infused at 0.4mU/Kg/Min Receives: Drug: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study; Drug: 0.8mU Insulin followed by withdrawal period followed by 0.4mU study
0.8mU Insulin	Other	During the euglycemic clamp insulin will be infused at 0.8mU/Kg/Min Receives: Drug: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study; Drug: 0.8mU Insulin followed by withdrawal period followed by 0.4mU study

What is being measured

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

Endogenous Glucose Production (EGP)
is calculated by tracer-based measurement and expressed per kg lean body mass
Measured: It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints

Timeline

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

14 Oct 20206 Jan 2022

First posted8 Jul 2020
Study start14 Oct 2020
Primary completion30 Jul 2021
Study completion6 Jan 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.
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: Crossover
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04461015
Sponsor's protocol ID: 20-001570
Status last verified: May 2022
First submitted: 30 Jun 2020
Last updated: 21 Jun 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans
ClinicalTrials.gov ID: NCT04461015
Acronym / sponsor ID: 20-001570
Conditions: Healthy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Adrian VellaUniversity, hospital or other
Study start: 14 Oct 2020 (actual)
Primary completion: 30 Jul 2021 (actual)
Study completion: 6 Jan 2022 (actual)
First posted: 8 Jul 2020 (actual)
Results: Posted 21 Jun 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
0.4mU Insulin	Other	Drug: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study, Drug: 0.8mU Insulin followed by withdrawal period followed by 0.4mU studyDuring the euglycemic clamp insulin will be infused at 0.4mU/Kg/Min
0.8mU Insulin	Other	Drug: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study, Drug: 0.8mU Insulin followed by withdrawal period followed by 0.4mU studyDuring the euglycemic clamp insulin will be infused at 0.8mU/Kg/Min

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

We will recruit 15 otherwise healthy subjects using intramural and local extramural advertising after approval from the Mayo Clinic Institutional Review Board. Individuals who express interest in participating will be invited for a screening visit. Individuals with a BMI < 19 or > 28 kg/m2 will be excluded from the study to avoid potential confounding effects that may result from extreme leanness or from obesity. Subjects will have no known systemic illness, taking any medication that could affect glucose metabolism and no history of upper gastrointestinal surgery.

Key exclusion criteria (1 listed)

Subjects < 18 years of age or > 40 years of age will not be studied to minimize the potential confounding effects of age on glucagon and insulin action. The subjects will not be taking medications that affect glucose metabolism (to be determined by PI) and have no history of chronic illness or upper gastrointestinal surgery. We are seeking to recruit subjects who do not have diabetes (fasting glucose <100mg/dL).

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
0.4mU Insulin followed by withdrawal period followed by 0.8mU studyAlso: 0.4 then 0.8Clamp study with insulin infused at 0.4 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.8 mU/Kg/min	Drug	0.4mU Insulin, 0.8mU Insulin
0.8mU Insulin followed by withdrawal period followed by 0.4mU studyAlso: 0.8 then 0.4Clamp study with insulin infused at 0.8 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.4 mU/Kg/min	Drug	0.4mU Insulin, 0.8mU Insulin

Primary outcome

Endogenous Glucose Production (EGP)
Time frame: It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints
is calculated by tracer-based measurement and expressed per kg lean body mass

Results and safety

Results posted to the registry on 21 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.4 Then 0.8	5	5
0.8 Then 0.4	7	5

Primary outcome: Endogenous Glucose Production (EGP)

Time frame: It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints. Mean (Standard Error). Unit: umol/kg/min

Measure	0.4mU Insulin n = 10	0.8mU Insulin n = 10
At 90 minutes	4.99 (0.53)	5.02 (0.74)
At 180 minutes	6.82 (0.82)	5.52 (0.96)
At 270 minutes	8.48 (1.07)	5.38 (1.13)

Adverse events

Time frame: 3 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0.4 Events	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
0.8 Events	0 of 12 (0%)	2 of 12 (16.7%)	0 of 12

Limitations and caveats (from the sponsor): The main caveat is that during the experiment insulin is kept constant - i.e. not quite like what happens in the postprandial situation

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Mayo Clinic Clinical TrialsLink provided by the sponsor.
Individual participant dataSharing planned: No

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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.

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?

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 1 inclusion and 1 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 21 Jun 2022. 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 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 21 Jun 2022). 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?

Endogenous Glucose Production (EGP) (time frame: It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints). 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 NCT04461015.

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 21 Jun 2022.