Type1diabetesGIPHYPONCT06137586
The Effect of Glucose-dependent Insulinotropic Polypeptide on the Alpha Cell Response to Hypoglycaemia in Patients with Type 1 Diabetes
A study of Type1diabetes and Hypoglycemia, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial summary
The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP[1-30] and GIP[1-42], in patients with type 1 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 70 years, men only
- Conditions the study is for
- Type1diabetes, Hypoglycemia, Type 1 Diabetes
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 10 Aug 2022to 17 May 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 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Caucasian men
- Body mass index between 18-27kg/m2
- Type 1 diabetes (T1D) (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/mol (<8.5%)
- T1D duration of 2-30 years
- C-peptide negative (stimulated C-peptide ≤ 100 pmol/l)
- Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
- Informed consent
Who cannot join
- Anaemia (haemoglobin below normal range)
- Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
- Late microvascular complications except mild nonproliferative retinopathy
- Allergy or intolerance to ingredients included in the standardized meals
- Prior myocardial infarction or other cardiac events
- Any physical or psychological condition that the investigator feels would interfere with trial participation
- Treatment with any glucose-lowering drugs beside insulin
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Gentofte Hospital
Hellerup, Copenhagen, 2900
About this study
The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP[1-30] and GIP[1-42], in patients with type 1 diabetes. The main question it aims to answer is:
- What dose and isoform of GIP can most potently stimulate glucagon secretion during low blood sugar in patients with type 1 diabetes?
Participants will go through 5 experimental days that are identical except for an intravenous infusion of either placebo (saline), high or low dose GIP[1-42] or high or low dose GIP[1-30]. On all days, blood sugar will be lowered to around 2.5mmol/l for around 20-30min.
Read the detailed description
After being informed about the study and the potential risks, each participant giving written informed consent will participate in five double-blinded experimental days (Day A-E) in a randomized order. Each experimental day is identical except for an intravenous infusion of either placebo (saline), high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-42] or high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-30].
Each experimental day will consist of an induction period where the participant's blood sugar is adjusted to around 5-6mmol/l with either insulin or glucose. Then the infusion of either placebo or hormone will be initiated and continued for 135 minutes.
After 30 minutes of hormone infusion, a separate infusion of insulin (1.5mU/kg/min) will be initiated and continued for 60 minutes. Based on frequent bed-side plasma glucose measurements and an adjustable 20% glucose infusion, plasma glucose will be clamped at 2.5 mmol/l until the insulin infusion is terminated. Following this is a 45 minute recovery period, during which a minimum of glucose is infused, to ensure a steady rise from 2.5mmol/l to 3.5mmol/l.
After the study day, patients will receive a meal to prevent subsequent hypoglycemia.
The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.
- Conditions
- Type1diabetes, Hypoglycemia, Type 1 Diabetes
- Being tested
- Infusion of GIP[1-42], GIP[1-30] or placebo
- Keywords
- Incretins, GIP, Glucose-dependent insulinotropic polypeptide, Alpha cell
- Medical subject headings
- Hypoglycemia, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of GIP[1-42], GIP[1-30] or placeboOther
This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP[1-42] B) 8pmol/kg/min GIP[1-42] C) 4pmol/kg/min GIP[1-30] D) 8pmol/kg/min GIP[1-30] E) Saline (placebo)
| Study group | Role | What they receive |
|---|---|---|
| Infusion of GIP[1-42], GIP[1-30] or placebo | Experimental | This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP[1-42] B) 8pmol/kg/min GIP[1-42] C) 4pmol/kg/min GIP[1-30] D) 8pmol/kg/min GIP[1-30] E) Saline (placebo) Receives: Other: Infusion of GIP[1-42], GIP[1-30] or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total glucagon response
Difference in baseline subtracted area under the curve (bsAUC) for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Secondary outcomes (14)
Glucagon response during insulin infusion
Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the insulin infusion
Measured: 30-90minutes
Glucagon response after blood glucose (BG) falls below 3.0 mmol/L
Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively in the 30 minutes following a blood glucose of below 3.0 mmol/L
Measured: t[BG<3.0] and the following 30 minutes
Glucagon response during recovery
Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the recovery period
Measured: 90-135minutes
Total insulin response
Difference in plasma levels of insulin between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Total c-peptide response
Difference in plasma levels of c-peptide between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Amount of glucose infused
Difference in infusion rates for glucose between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in epinephrine
Difference in plasma levels of epinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in norepinephrine
Difference in plasma levels of norepinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in cortisol
Difference in plasma levels of cortisol between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in growth hormone hormones
Difference in plasma levels of growth hormone between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)
Difference in plasma levels of P1NP between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in carboxy-terminal collagen crosslinks (CTX)
Difference in plasma levels of CTX between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in blood pressure
Difference in blood pressure between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Difference in heart rate
Difference in heart rate between study days with GIP[1-42], GIP[1-30] and placebo, respectively
Measured: 0-135minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start10 Aug 2022
- Primary completion17 May 2024
- Study completion17 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type1diabetesStudies 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 five 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
- NCT06137586
- Sponsor's protocol ID
- GIPHYPO2022
- Acronym
- GIPHYPO
- 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
- The Effect of Glucose-dependent Insulinotropic Polypeptide on the Alpha Cell Response to Hypoglycaemia in Patients with Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT06137586
- Acronym / sponsor ID
- GIPHYPO / GIPHYPO2022
- Conditions
- Type1diabetes, Hypoglycemia, Type 1 Diabetes
- Keywords
- Incretins, GIP, Glucose-dependent insulinotropic polypeptide, Alpha cell
- 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
- 10 Aug 2022 (actual)
- Primary completion
- 17 May 2024 (actual)
- Study completion
- 17 May 2024 (actual)
- First posted
- 18 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.
The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP[1-30] and GIP[1-42], in patients with type 1 diabetes. The main question it aims to answer is:
- What dose and isoform of GIP can most potently stimulate glucagon secretion during low blood sugar in patients with type 1 diabetes?
Participants will go through 5 experimental days that are identical except for an intravenous infusion of either placebo (saline), high or low dose GIP[1-42] or high or low dose GIP[1-30]. On all days, blood sugar will be lowered to around 2.5mmol/l for around 20-30min.
Detailed description
After being informed about the study and the potential risks, each participant giving written informed consent will participate in five double-blinded experimental days (Day A-E) in a randomized order. Each experimental day is identical except for an intravenous infusion of either placebo (saline), high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-42] or high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-30].
Each experimental day will consist of an induction period where the participant's blood sugar is adjusted to around 5-6mmol/l with either insulin or glucose. Then the infusion of either placebo or hormone will be initiated and continued for 135 minutes.
After 30 minutes of hormone infusion, a separate infusion of insulin (1.5mU/kg/min) will be initiated and continued for 60 minutes. Based on frequent bed-side plasma glucose measurements and an adjustable 20% glucose infusion, plasma glucose will be clamped at 2.5 mmol/l until the insulin infusion is terminated. Following this is a 45 minute recovery period, during which a minimum of glucose is infused, to ensure a steady rise from 2.5mmol/l to 3.5mmol/l.
After the study day, patients will receive a meal to prevent subsequent hypoglycemia.
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 five experimental days in a randomized order - acting as their own controls
| Arm | Type | Receives |
|---|---|---|
| Infusion of GIP[1-42], GIP[1-30] or placebo | Experimental | Other: Infusion of GIP[1-42], GIP[1-30] or placeboThis is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP[1-42] B) 8pmol/kg/min GIP[1-42] C) 4pmol/kg/min GIP[1-30] D) 8pmol/kg/min GIP[1-30] E) Saline (placebo) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Caucasian men
- Body mass index between 18-27kg/m2
- Type 1 diabetes (T1D) (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/mol (<8.5%)
- T1D duration of 2-30 years
- C-peptide negative (stimulated C-peptide ≤ 100 pmol/l)
Key exclusion criteria (7 listed)
- Anaemia (haemoglobin below normal range)
- Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
- Late microvascular complications except mild nonproliferative retinopathy
- Allergy or intolerance to ingredients included in the standardized meals
- Prior myocardial infarction or other cardiac events
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 GIP[1-42], GIP[1-30] or placeboThis is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP[1-42] B) 8pmol/kg/min GIP[1-42] C) 4pmol/kg/min GIP[1-30] D) 8pmol/kg/min GIP[1-30] E) Saline (placebo) | Other | Infusion of GIP[1-42], GIP[1-30] or placebo |
Primary outcome
Total glucagon response
Time frame: 0-135minutes
Difference in baseline subtracted area under the curve (bsAUC) for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively
14 secondary outcomes
Glucagon response during insulin infusion
Time frame: 30-90minutes
Glucagon response after blood glucose (BG) falls below 3.0 mmol/L
Time frame: t[BG<3.0] and the following 30 minutes
Glucagon response during recovery
Time frame: 90-135minutes
Total insulin response
Time frame: 0-135minutes
Total c-peptide response
Time frame: 0-135minutes
Amount of glucose infused
Time frame: 0-135minutes
Difference in epinephrine
Time frame: 0-135minutes
Difference in norepinephrine
Time frame: 0-135minutes
Difference in cortisol
Time frame: 0-135minutes
Difference in growth hormone hormones
Time frame: 0-135minutes
Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)
Time frame: 0-135minutes
Difference in carboxy-terminal collagen crosslinks (CTX)
Time frame: 0-135minutes
Difference in blood pressure
Time frame: 0-135minutes
Difference in heart rate
Time frame: 0-135minutes
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 Type1diabetes 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 7 inclusion and 7 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: 0-135minutes). 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.