Neuronostatin - a Glucagonotropic Agent in Humans?

NCT ID: NCT06143267

Last Updated: 2024-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-06

Study Completion Date

2024-09-25

Brief Summary

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With the present study the investigators wish to delineate the effects of neuronostatin-13 (NST) on glucose-dependent glucagon secretion in humans. The main question it aims to answer is:

• What are the physiological effects of the naturally occuring hormone NST - especially with regards to glucagonotropic effects at different plasma glucose concentrations

In a randomized, double-blind crossover design, participants will undergo six experimental days with controlled plasma glucose levels, consisting of two euglycemic, two hyperglycemic (around 8mmol/l), and two hypoglycemic (around 2.5mmol/l) days, with each pair of similar days involving the administration of either saline (placebo) or NST.

Detailed Description

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With the present study the investigators wish to delineate the effects of neuronostatin on glucose-dependent glucagon secretion in humans. Thus, this study is designed to elucidate the physiological effects of the natural occurring hormone, neuronostatin, and not to examine a medical effect of a drug or treatment. However, if neuronostatin acts glucagonotropically during low plasma glucose concentrations it could potentially help to address the unmet medical need for a treatment that, ultimately, can counteract the high risk of hypoglycaemia in patients treated with insulin.

After being informed about the study and the potential risks, each participant giving written informed consent will participate in six double-blinded experimental days (Day A-F) in a randomized order. On each day, participants will receive an infusion of either saline (placebo)(day A, C and E) or NST (day B, D and F). On day A and B, blood glucose will be kept at fasting levels, on day C and D blood glucose will be increased to \~8mmol/l and on day E and F blood glucose will be lowered to \~2.5mmol/l.

Blood glucose will be adjusted with insulin and/or glucose to reach the desired levels on each day.

At the end of the study day, participants will receive an ad libitum meal.

The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.

Conditions

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Type 1 Diabetes Hypoglycemia Type1diabetes

Keywords

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Gut hormones Alpha cell Pancreas Incretins

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Randomized, double-blinded, single-arm study. Each participant goes through six experimental days in a randomized order - acting as their own controls
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

The randomized order of infusions is blinded to both participant and investigator

Study Groups

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Infusion of NST or placebo at different blood glucose levels

In a randomized, double-blind crossover design, participants will undergo six experimental days with controlled plasma glucose levels, consisting of two euglycemic, two hyperglycemic (around 8mmol/l), and two hypoglycemic (around 2.5mmol/l) days, with each pair of similar days involving the administration of either saline (placebo) or NST.

Group Type EXPERIMENTAL

Infusion of either NST or placebo at different blood glucose levels

Intervention Type OTHER

In a randomized, double-blind crossover design, participants will undergo six experimental days with controlled plasma glucose levels, consisting of two euglycemic, two hyperglycemic (around 8mmol/l), and two hypoglycemic (around 2.5mmol/l) days, with each pair of similar days involving the administration of either saline (placebo) or NST.

Interventions

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Infusion of either NST or placebo at different blood glucose levels

In a randomized, double-blind crossover design, participants will undergo six experimental days with controlled plasma glucose levels, consisting of two euglycemic, two hyperglycemic (around 8mmol/l), and two hypoglycemic (around 2.5mmol/l) days, with each pair of similar days involving the administration of either saline (placebo) or NST.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Normal haemoglobin \>8.3 mmol/l
* Normal fasting plasma glucose below 7 mmol/l
* Normal HbA1C \<42 mmol/mol (6%)
* Body mass index (BMI) 18.5-27 kg/m2
* Oral and written informed consent

Exclusion Criteria

* Diabetes
* Treatment with drugs that might interfere with glucose metabolism within a month prior to the research study
* Treatment with any medication that cannot be paused for 12 hours
* Known liver disease and/or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>2 × normal values
* Nephropathy (eGFR \<60 ml/min and/or albuminuria)
* Any condition that the investigator feels would interfere with trial participation
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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The Novo Nordisk Foundation Center for Basic Metabolic Research

OTHER

Sponsor Role collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Asger Lund, MD

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, , Denmark

Site Status

Countries

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Denmark

Other Identifiers

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NSTCLAMP

Identifier Type: -

Identifier Source: org_study_id