Neuronostatin - a Glucagonotropic Agent in Humans? (NSTCLAMP)

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Hypoglycemia; Type 1 Diabetes; Type1diabetes

Treatments: Other: Infusion of either NST or placebo at different blood glucose levels

Study type: Interventional

Funder types: Other

Identifiers

NCT06143267

NSTCLAMP

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 10 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Infusion of NST or placebo at different blood glucose levels

Experimental group

Description:

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.

Treatment:

Other: Infusion of either NST or placebo at different blood glucose levels