Glucose Metabolism DisordersBrainInsPPMNCT06295640
Relative Contribution of Brain Insulin Action for Postprandial Metabolism
A study testing Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray in people with Glucose Metabolism Disorders, run by University of Ulm at 1 site in Germany.
Trial summary
The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Glucose Metabolism Disorders
- What is being tested?
- Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteGermany
- Study dates
- 18 Mar 2024to Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI < 24 kg/m2
- no known primary diseases
- no hormonal contraception
Who cannot join
- Alcohol or drug abuse
- Smoking
- At screening: Hb < 12 g/dl for women and Hb < 14 g/dl for men
- Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women.
Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.
Read the detailed description
This research project aims to investigate to what extent brain insulin action is responsible for the control of postprandial metabolism compared to direct effects of insulin in peripheral target tissues. Furthermore, the study will investigate sex differences and the influence of the menstrual cycle on brain-derived coordination of postprandial signaling for metabolic control.
Therefore, insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 15 minutes before a 75 gram oral glucose tolerance test that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. This approach will be combined with a double-tracer dilution technique. Labeled glucose ([6,6-2H]glucose) will be infused 120 minutes before and during the OGTT (180 min) and will be used to address endogenous glucose production. The glucose drink from the OGTT will be enriched with [U-13C6]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd). Using this approach, brain-derived regulation of postprandial metabolism including endogenous glucose production, glucose disappearance, insulin secretion, and secretion of proglucagon-cleavage products (incretins) will be examined.
- Conditions
- Glucose Metabolism Disorders
- Being tested
- Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray, Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray
- Keywords
- postprandial glucose metabolism, brain insulin action, insulin sensitivity, insulin secretion, endogenous glucose production, menstrual cycle, sex differences, proglucagon cleavage products
- Medical subject headings
- Glucose Metabolism Disorders, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral glucose tolerance test with double-tracer dilution and intranasal insulin sprayOther
Subjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. [6,6-2H]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Intranasal insulin will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with [U-13C6]-glucose.
Oral glucose tolerance test with double-tracer dilution and intranasal placebo sprayOther
Subjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. [6,6-2H]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Placebo spray will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with [U-13C6]-glucose. To mimic insulin spill-over from nasal spray into systemic circulation, an i.v. insulin bolus of 3 mU × kg-1. will be administered over ten minutes starting at time point -15 minutes on the placebo spray day. On the insulin spray day a comparable amount of saline will be infused.
| Study group | Role | What they receive |
|---|---|---|
| Intranasal insulin spray | Experimental | 160 Units of human insulin as nasal spray Receives: Other: Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray |
| Placebo spray | Placebo comparator | Nasal spray containing placebo solution Receives: Other: Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endogenous glucose production
Effect of intranasal insulin versus placebo on endogenous glucose production assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
Measured: -120 minutes - 180 minutes during oral glucose tolerance test
Rate of glucose disappearance
Effect of intranasal insulin versus placebo on rate of glucose disappearance (Rd) assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
Measured: -120 minutes - 180 minutes during oral glucose tolerance test
Secondary outcomes (8)
Proglucagon cleavage products
Effect of intranasal insulin versus placebo on secretion of proglucagon cleavage products assessed by oral glucose tolerance test.
Measured: 0-120 minutes during oral glucose tolerance test
Glucose tolerance
Effect of intranasal insulin versus placebo on glucose tolerance assessed as area under the glucose curve (0-120 minutes) and glucose levels at timepoint 120 minutes during the 75 g oral glucose tolerance test.
Measured: 0-120 minutes during oral glucose tolerance test
Whole-body insulin sensitivity
Effect of intranasal insulin versus placebo on whole-body insulin sensitivity, assessed from glucose and insulin measurements during the 75 g OGTT.
Measured: 0-120 minutes during oral glucose tolerance test
Insulin secretion
Effect of intranasal insulin versus placebo on insulin secretion assessed from glucose and insulin/C-peptide measurements during the 75 g oral glucose tolerance test.
Measured: 0-180 minutes during oral glucose tolerance test
Post-absorptive energy expenditure
Effect of intranasal insulin versus placebo on post-absorptive energy expenditure assessed by indirect calorimetry at timepoint 30 min and 180 min during an oral glucose tolerance test combined with double-tracer dilution technique.
Measured: 30 minutes and 180 minutes during oral glucose tolerance test
Sex differences
Explore sex differences in the brain-derived regulation of postprandial metabolism during the 75 g oral glucose tolerance tests. Outcomes 1-7 will be compared between sexes.
Measured: -120 minutes - 180 minutes during oral glucose tolerance test
Menstrual cycle effects
Differences between the follicular and the luteal phase of the menstrual cycle in the brain-derived regulation of postprandial metabolism during the 75 g oral glucose tolerance tests: Outcomes 1-7 will be compared between the phases of the menstrual cycle.
Measured: -120 minutes - 180 minutes during oral glucose tolerance test
Autonomic nervous system activity
Effect of intranasal insulin versus placebo on autonomic nervous system activity assessed by heart rate variability using an 3-channel ECG at timepoint -15 min until 180 min during an oral glucose tolerance test combined with double-tracer dilution technique.
Measured: -15 minutes - 180 minutes during oral glucose tolerance test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2024
- Study start18 Mar 2024
- Primary completion5 Sep 2025
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glucose Metabolism DisordersStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, controlled, cross-over design for men. Randomized, controlled, 2x2 factorial cross-over design for women taking the menstrual cycle phase into account.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Ulm
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Martin Heni, University of Ulm
- Investigators
- Martin Heni, MD, Principal investigator, University of Ulm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06295640
- Sponsor's protocol ID
- 300/2022
- Acronym
- BrainInsPPM
- Status last verified
- Nov 2025
- First submitted
- 8 Feb 2024
- Last updated
- 17 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relative Contribution of Brain Insulin Action for Postprandial Metabolism
- ClinicalTrials.gov ID
- NCT06295640
- Acronym / sponsor ID
- BrainInsPPM / 300/2022
- Conditions
- Glucose Metabolism Disorders
- Keywords
- postprandial glucose metabolism, brain insulin action, insulin sensitivity, insulin secretion, endogenous glucose production, menstrual cycle, sex differences, proglucagon cleavage products
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of UlmUniversity, hospital or other
- Study start
- 18 Mar 2024 (actual)
- Primary completion
- 5 Sep 2025 (actual)
- Study completion
- Jun 2026 (estimated)
- First posted
- 6 Mar 2024 (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 clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women.
Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.
Detailed description
This research project aims to investigate to what extent brain insulin action is responsible for the control of postprandial metabolism compared to direct effects of insulin in peripheral target tissues. Furthermore, the study will investigate sex differences and the influence of the menstrual cycle on brain-derived coordination of postprandial signaling for metabolic control.
Therefore, insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 15 minutes before a 75 gram oral glucose tolerance test that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. This approach will be combined with a double-tracer dilution technique. Labeled glucose ([6,6-2H]glucose) will be infused 120 minutes before and during the OGTT (180 min) and will be used to address endogenous glucose production. The glucose drink from the OGTT will be enriched with [U-13C6]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd). Using this approach, brain-derived regulation of postprandial metabolism including endogenous glucose production, glucose disappearance, insulin secretion, and secretion of proglucagon-cleavage products (incretins) will be examined.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized, controlled, cross-over design for men. Randomized, controlled, 2x2 factorial cross-over design for women taking the menstrual cycle phase into account.
| Arm | Type | Receives |
|---|---|---|
| Intranasal insulin spray | Experimental | Other: Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray160 Units of human insulin as nasal spray |
| Placebo spray | Placebo comparator | Other: Oral glucose tolerance test with double-tracer dilution and intranasal placebo sprayNasal spray containing placebo solution |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- BMI < 24 kg/m2
- no known primary diseases
- no hormonal contraception
Key exclusion criteria (4 listed)
- Alcohol or drug abuse
- Smoking
- At screening: Hb < 12 g/dl for women and Hb < 14 g/dl for men
- Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.
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 |
|---|---|---|
| Oral glucose tolerance test with double-tracer dilution and intranasal insulin spraySubjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. [6,6-2H]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Intranasal insulin will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with [U-13C6]-glucose. | Other | Intranasal insulin spray |
| Oral glucose tolerance test with double-tracer dilution and intranasal placebo spraySubjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. [6,6-2H]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Placebo spray will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with [U-13C6]-glucose. To mimic insulin spill-over from nasal spray into systemic circulation, an i.v. insulin bolus of 3 mU × kg-1. will be administered over ten minutes starting at time point -15 minutes on the placebo spray day. On the insulin spray day a comparable amount of saline will be infused. | Other | Placebo spray |
Primary outcome
Endogenous glucose production
Time frame: -120 minutes - 180 minutes during oral glucose tolerance test
Effect of intranasal insulin versus placebo on endogenous glucose production assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
Rate of glucose disappearance
Time frame: -120 minutes - 180 minutes during oral glucose tolerance test
Effect of intranasal insulin versus placebo on rate of glucose disappearance (Rd) assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
8 secondary outcomes
Proglucagon cleavage products
Time frame: 0-120 minutes during oral glucose tolerance test
Glucose tolerance
Time frame: 0-120 minutes during oral glucose tolerance test
Whole-body insulin sensitivity
Time frame: 0-120 minutes during oral glucose tolerance test
Insulin secretion
Time frame: 0-180 minutes during oral glucose tolerance test
Post-absorptive energy expenditure
Time frame: 30 minutes and 180 minutes during oral glucose tolerance test
Sex differences
Time frame: -120 minutes - 180 minutes during oral glucose tolerance test
Menstrual cycle effects
Time frame: -120 minutes - 180 minutes during oral glucose tolerance test
Autonomic nervous system activity
Time frame: -15 minutes - 180 minutes during oral glucose tolerance test
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
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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.
Martin Heni, MD principal investigator
University of Ulm
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray in people with Glucose Metabolism Disorders, run by University of Ulm at 1 site in Germany.
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 3 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 17 Feb 2026. 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 Germany. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
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?
Endogenous glucose production (time frame: -120 minutes - 180 minutes during oral glucose tolerance test). The study lists 2 primary outcomes in all. 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 17 Feb 2026.