Type 1 DiabetesNSTCLAMPNCT06143267
Neuronostatin - a Glucagonotropic Agent in Humans?
A study of Type 1 Diabetes and Hypoglycemia, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes, Hypoglycemia, Type1diabetes
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 6 Dec 2022to 25 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Gentofte Hospital
Hellerup, 2900
About this study
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.
Read the 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.
- Conditions
- Type 1 Diabetes, Hypoglycemia, Type1diabetes
- Being tested
- Infusion of either NST or placebo at different blood glucose levels
- Keywords
- Gut hormones, Alpha cell, Pancreas, Incretins
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of either NST or placebo at different blood glucose levelsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Infusion of either NST or placebo at different blood glucose levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total glucagon response
Differences in glucagon responses, measured as baseline subtracted AUC (bsAUC), between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Secondary outcomes (18)
Glucagon response during first 60 minutes
Differences in bsAUC for glucagon between days with neuronostatin and placebo at corresponding glucose concentrations, respectively, from 0 to 60minutes
Measured: 0-60minutes
Glucagon response during "recovery"
Differences in bsAUC for glucagon between days with neuronostatin and placebo at corresponding glucose concentrations, respectively, from 60 to 90minutes
Measured: 60-90minutes
Glucagon response during hypoglycemia
Difference in bsAUC for glucagon between the two hypoglycemic study days with NST and placebo, respectively in the 30 minutes following a blood glucose (BG) below 3.0mmol/L
Measured: t[BG=3.0] and the following 30 minutes
Total insulin response
Difference in plasma levels of insulin between study days between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Total proinsulin-c-peptide response
Difference in plasma levels of proinsulin-c-peptide between study days between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Amount of glucose infused
Difference in infusion rates for glucose between study days between days with neuronostatin and placebo, respectively, at both hyperglycemic and hypoglycemic days
Measured: 0-150minutes
Difference in epinephrine
Difference in plasma levels of epinephrine between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in norepinephrine
Difference in plasma levels of norepinephrine between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in cortisol
Difference in plasma levels of cortisol between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in growth hormone
Difference in plasma levels of growth hormone between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)
Difference in plasma levels of P1NP between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in osteocalcin
Difference in plasma levels of osteocalcin between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in carboxy-terminal collagen crosslinks (CTX)
Difference in plasma levels of CTX between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in blood pressure
Difference in blood pressure between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Difference in heart rate
Difference in heart rate between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: 0-150minutes
Energy expenditure
Difference in energy expenditure (measured by indirect calorimetry measuring respiratory gas exchange) between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: At -20 minutes, at 30 minutes, and at 75 minutes
Appetite
Difference in appetite (assessed by visual analogue scale) between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: At -5 minutes, 25 minutes, 60 minutes, 90 minutes, and 120minutes
Food intake
Difference in food intake (assessed by ad libitum meal) between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
Measured: At 125 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2023
- Study start6 Dec 2022
- Primary completion25 Sep 2024
- Study completion25 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Randomized, double-blinded, single-arm study. Each participant goes through six experimental days in a randomized order - acting as their own controls
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- The Novo Nordisk Foundation Center for Basic Metabolic Research
- Responsible party
- Principal investigator, Asger Lund, MD, University Hospital, Gentofte, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06143267
- Sponsor's protocol ID
- NSTCLAMP
- Acronym
- NSTCLAMP
- Status last verified
- Nov 2024
- First submitted
- 9 Nov 2023
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All published data will be made available to other researchers upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuronostatin - a Glucagonotropic Agent in Humans?
- ClinicalTrials.gov ID
- NCT06143267
- Acronym / sponsor ID
- NSTCLAMP / NSTCLAMP
- Conditions
- Type 1 Diabetes, Hypoglycemia, Type1diabetes
- Keywords
- Gut hormones, Alpha cell, Pancreas, Incretins
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Collaborators
- The Novo Nordisk Foundation Center for Basic Metabolic Research
- Study start
- 6 Dec 2022 (actual)
- Primary completion
- 25 Sep 2024 (actual)
- Study completion
- 25 Sep 2024 (actual)
- First posted
- 22 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Randomized, double-blinded, single-arm study. Each participant goes through six experimental days in a randomized order - acting as their own controls
| Arm | Type | Receives |
|---|---|---|
| Infusion of NST or placebo at different blood glucose levels | Experimental | Other: Infusion of either NST or placebo at different blood glucose levelsIn 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
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 |
|---|---|---|
| Infusion of either NST or placebo at different blood glucose levelsIn 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 NST or placebo at different blood glucose levels |
Primary outcome
Total glucagon response
Time frame: 0-150minutes
Differences in glucagon responses, measured as baseline subtracted AUC (bsAUC), between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
18 secondary outcomes
Glucagon response during first 60 minutes
Time frame: 0-60minutes
Glucagon response during "recovery"
Time frame: 60-90minutes
Glucagon response during hypoglycemia
Time frame: t[BG=3.0] and the following 30 minutes
Total insulin response
Time frame: 0-150minutes
Total proinsulin-c-peptide response
Time frame: 0-150minutes
Amount of glucose infused
Time frame: 0-150minutes
Difference in epinephrine
Time frame: 0-150minutes
Difference in norepinephrine
Time frame: 0-150minutes
Difference in cortisol
Time frame: 0-150minutes
Difference in growth hormone
Time frame: 0-150minutes
Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)
Time frame: 0-150minutes
Difference in osteocalcin
Time frame: 0-150minutes
Difference in carboxy-terminal collagen crosslinks (CTX)
Time frame: 0-150minutes
Difference in blood pressure
Time frame: 0-150minutes
Difference in heart rate
Time frame: 0-150minutes
Energy expenditure
Time frame: At -20 minutes, at 30 minutes, and at 75 minutes
Appetite
Time frame: At -5 minutes, 25 minutes, 60 minutes, 90 minutes, and 120minutes
Food intake
Time frame: At 125 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- Individual participant dataSharing planned: Yes. All published data will be made available to other researchers upon reasonable request
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Type 1 Diabetes and Hypoglycemia, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
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 5 inclusion and 6 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 10 Dec 2024. 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 Denmark. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Total glucagon response (time frame: 0-150minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Dec 2024.