Clinical trial NCT06143267: Neuronostatin - a Glucagonotropic Agent in Humans?
Official title: Neuronostatin - a Glucagonotropic Agent in Humans?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Hypoglycemia
Type1diabetes
Keywords: Gut hormones
Alpha cell
Pancreas
Incretins
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: The Novo Nordisk Foundation Center for Basic Metabolic Research
First posted: 2023-11-22
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Randomized, double-blinded, single-arm study. Each participant goes through six experimental days in a randomized order - acting as their own controls
Primary purpose: BASIC_SCIENCE

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total glucagon response
timeFrame: 0-150minutes
Secondary outcomes:
measure: Glucagon response during first 60 minutes
timeFrame: 0-60minutes
measure: Glucagon response during "recovery"
timeFrame: 60-90minutes
measure: Glucagon response during hypoglycemia
timeFrame: t[BG=3.0] and the following 30 minutes
measure: Total insulin response
timeFrame: 0-150minutes
measure: Total proinsulin-c-peptide response
timeFrame: 0-150minutes
measure: Amount of glucose infused
timeFrame: 0-150minutes
measure: Difference in epinephrine
timeFrame: 0-150minutes
measure: Difference in norepinephrine
timeFrame: 0-150minutes
measure: Difference in cortisol
timeFrame: 0-150minutes
measure: Difference in growth hormone
timeFrame: 0-150minutes
measure: Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)
timeFrame: 0-150minutes
measure: Difference in osteocalcin
timeFrame: 0-150minutes
measure: Difference in carboxy-terminal collagen crosslinks (CTX)
timeFrame: 0-150minutes
measure: Difference in blood pressure
timeFrame: 0-150minutes
measure: Difference in heart rate
timeFrame: 0-150minutes
measure: Energy expenditure
timeFrame: At -20 minutes, at 30 minutes, and at 75 minutes
measure: Appetite
timeFrame: At -5 minutes, 25 minutes, 60 minutes, 90 minutes, and 120minutes
measure: Food intake
timeFrame: At 125 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research, Gentofte Hospital
Study officials:
References: