Insulin ResistancePhase 1/2NI EGP highBMINCT03383822
Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance
A Phase 1/2 study testing Intranasal insulin in people with Insulin Resistance, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
It is well known that the hormone insulin lowers blood glucose in part by acting directly on the liver and reducing hepatic glucose production. Animal studies have shown that the hormone insulin can act on the brain to indirectly lower glucose production by the liver. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- Intranasal insulin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteCanada
- Study dates
- 8 Sep 2015to 1 Dec 2017
- Phase
- Phase 1/2
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women, aged 18 to 60 years
- Body mass index >30 kg/m2
- Hemoglobin in the normal range.
- Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test
- Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study.
Who cannot join
- Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years.
- Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.
- Any current or previous history of endocrine disease, dyslipidemia or malignancy
- Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic BP > 100 or systolic > 180 or systolic BP<100) or proliferative retinopathy
- Use of immunosuppressive agents at any time during the study
- Allergy to any study medication
Show all 17Show fewer
- Pregnancy or breastfeeding
- Heavy smoker
- Prior nasoduodenal tube insertion under fluoroscopic guidance.
- Fasting blood glucose > 6.0 mmol/l or known diabetes.
- Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on electrocardiogram, unstable angina, or decompensated heart failure.
- Any nasal pathology likely to affect absorption of insulin or insertion of nasoduodenal tube.
- Any laboratory values: aspartate transaminase > 2x upper limit of normal; alanine aminotransferase > 2x upper limit of normal; thyroid-stimulating hormone > 6 micro unit/l
- Current addiction to alcohol or substances of abuse as determined by the investigator.
- Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
- Taking any regular prescription or non-prescription medications at the time of the study. Occasional use of medications such as acetoaminophen or Tylenol 1 or any use of natural health products may be permitted at the discretion of the investigator.
- Will not donate blood three months prior to and three months post study procedures
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Egulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance
It is well known that the hormone insulin lowers blood glucose in part by acting directly on the liver and reducing hepatic glucose production. Animal studies have shown that the hormone insulin can act on the brain to indirectly lower glucose production by the liver. It has previously been shown that a nasal spray can deliver insulin directly to the brain without affecting circulating insulin concentration in humans. Intranasal spray of insulin suppressed hepatic glucose production in lean subjects. It is unknown whether this effects is blunted in subjects with insulin resistance.
Read the detailed description
Each study participant will be admitted to hospital the evening prior to the study. Following admission each study participant will be provided with a standardized dinner. At 7am (t=0) the next day we will begin a primed, constant intravenous infusion d2 glucose (a stable isotope of glucose, the enrichment of which can be measured by gas chromatography mass spectrometry, allowing us to calculate endogenous glucose production rates) and continue this for 8 hours. At the same time (7am) a pancreatic clamp will be started as described above for 8 hours. Blood samples will be analysed with a glucometer for instant blood glucose readings At 9 am (+120 minutes) intranasal placebo or insulin will be administered. The insulin (Humalog Lispro 100 IU/ml, Eli Lily, Canada) and placebo (diluent) will be transferred to a metered nasal device (Pharmasystems, Ontario #063636 802721, Item 10271) immediately prior to use. This device dispenses 0.1ml (10 IU) per puff. 4 x 0.1 ml puffs/vials (2 per nostril) will be administered at rate of 2 (one in each nostril) every 60 seconds. Blood will be drawn at t=0, 30, 60, 120 and every 10 minutes thereafter for 6 hours. In order to match peripheral lispro concentrations between study visits, a small dose of Humalog (lispro) insulin will be administered intravenously at 9am, during the placebo arm of the study. Based on the pharmacokinetics of Humalog lispro (personal communication from Eli Lilly), we propose to administer 0.005 IU/kg over 30 minutes. 20% dextrose will be administered to maintain euglycemia as necessary. Insulin, glucagon, and glucose isotopic enrichment will be measured. The enrichment data and glucose infusion will be used to calculate steady state glucose production.
- Conditions
- Insulin Resistance
- Being tested
- Intranasal insulin, Intranasal placebo
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal insulinDrug
Also called Insulin
Humalog lispro 40 IU intranasally
Intranasal placeboDrug
Also called Placebo
Diluent intranasally
| Study group | Role | What they receive |
|---|---|---|
| Intranasal insulin | Experimental | 40 IU of intranasal insulin Receives: Drug: Intranasal insulin |
| Intranasal placebo | Placebo comparator | Placebo comparator to intranasal insulin Receives: Drug: Intranasal placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endogenous glucose production
Effects of intranasal insulin and placebo on endogenous glucose production will be assessed
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start8 Sep 2015
- Primary completion31 Jul 2017
- Study completion1 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03383822
- Sponsor's protocol ID
- NI EGP highBMI 12-5032A
- Acronym
- NI EGP highBMI
- Status last verified
- Dec 2017
- First submitted
- 19 Dec 2017
- Last updated
- 26 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Egulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance
- ClinicalTrials.gov ID
- NCT03383822
- Acronym / sponsor ID
- NI EGP highBMI / NI EGP highBMI 12-5032A
- Conditions
- Insulin Resistance
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 8 Sep 2015 (actual)
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 1 Dec 2017 (actual)
- First posted
- 26 Dec 2017 (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.
It is well known that the hormone insulin lowers blood glucose in part by acting directly on the liver and reducing hepatic glucose production. Animal studies have shown that the hormone insulin can act on the brain to indirectly lower glucose production by the liver. It has previously been shown that a nasal spray can deliver insulin directly to the brain without affecting circulating insulin concentration in humans. Intranasal spray of insulin suppressed hepatic glucose production in lean subjects. It is unknown whether this effects is blunted in subjects with insulin resistance.
Detailed description
Each study participant will be admitted to hospital the evening prior to the study. Following admission each study participant will be provided with a standardized dinner. At 7am (t=0) the next day we will begin a primed, constant intravenous infusion d2 glucose (a stable isotope of glucose, the enrichment of which can be measured by gas chromatography mass spectrometry, allowing us to calculate endogenous glucose production rates) and continue this for 8 hours. At the same time (7am) a pancreatic clamp will be started as described above for 8 hours. Blood samples will be analysed with a glucometer for instant blood glucose readings At 9 am (+120 minutes) intranasal placebo or insulin will be administered. The insulin (Humalog Lispro 100 IU/ml, Eli Lily, Canada) and placebo (diluent) will be transferred to a metered nasal device (Pharmasystems, Ontario #063636 802721, Item 10271) immediately prior to use. This device dispenses 0.1ml (10 IU) per puff. 4 x 0.1 ml puffs/vials (2 per nostril) will be administered at rate of 2 (one in each nostril) every 60 seconds. Blood will be drawn at t=0, 30, 60, 120 and every 10 minutes thereafter for 6 hours. In order to match peripheral lispro concentrations between study visits, a small dose of Humalog (lispro) insulin will be administered intravenously at 9am, during the placebo arm of the study. Based on the pharmacokinetics of Humalog lispro (personal communication from Eli Lilly), we propose to administer 0.005 IU/kg over 30 minutes. 20% dextrose will be administered to maintain euglycemia as necessary. Insulin, glucagon, and glucose isotopic enrichment will be measured. The enrichment data and glucose infusion will be used to calculate steady state glucose production.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intranasal insulin | Experimental | Drug: Intranasal insulin40 IU of intranasal insulin |
| Intranasal placebo | Placebo comparator | Drug: Intranasal placeboPlacebo comparator to intranasal insulin |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men and women, aged 18 to 60 years
- Body mass index >30 kg/m2
- Hemoglobin in the normal range.
- Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test
- Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study.
Key exclusion criteria (17 listed)
- Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years.
- Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.
- Any current or previous history of endocrine disease, dyslipidemia or malignancy
- Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic BP > 100 or systolic > 180 or systolic BP<100) or proliferative retinopathy
- Use of immunosuppressive agents at any time during the study
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 |
|---|---|---|
| Intranasal insulinAlso: InsulinHumalog lispro 40 IU intranasally | Drug | Intranasal insulin |
| Intranasal placeboAlso: PlaceboDiluent intranasally | Drug | Intranasal placebo |
Primary outcome
Endogenous glucose production
Time frame: 8 hours
Effects of intranasal insulin and placebo on endogenous glucose production will be assessed
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 26 Dec 2017.
- Individual participant dataSharing planned: No
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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 Phase 1/2 study testing Intranasal insulin in people with Insulin Resistance, run by University Health Network, Toronto at 1 site in Canada.
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 17 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 26 Dec 2017. 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 Canada. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Endogenous glucose production (time frame: 8 hours). 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 26 Dec 2017.