Neuronostatin - a Glucagonotropic Agent in Humans?

NCT06143267 | Completed DMC

• 1 other identifier: NSTCLAMP
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes; Hypoglycemia; Type1diabetes

Keywords

Gut hormones; Alpha cell; Pancreas; Incretins

Outcome Measures

Primary Outcomes (1)

• Total glucagon response

  Differences in glucagon responses, measured as baseline subtracted AUC (bsAUC), between days with neuronostatin and placebo at corresponding glucose concentrations, respectively

  0-150minutes

Secondary Outcomes (18)

• Glucagon response during first 60 minutes

  0-60minutes

• Glucagon response during "recovery"

  60-90minutes

• Glucagon response during hypoglycemia

  t[BG=3.0] and the following 30 minutes

• Total insulin response

  0-150minutes

• Total proinsulin-c-peptide response

  0-150minutes

Study Arms (1)

Infusion of NST or placebo at different blood glucose levels

EXPERIMENTAL

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.

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

Interventions

Infusion of either NST or placebo at different blood glucose levels 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.

Infusion of NST or placebo at different blood glucose levels

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• The Novo Nordisk Foundation Center for Basic Metabolic Research: collaborator

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: The randomized order of infusions is blinded to both participant and investigator
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

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

Study Record Dates

• First Submitted: November 9, 2023
• First Posted: November 22, 2023
• Study Start: December 6, 2022
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)