Insulin Resistance, DiabetesPhase 1Nasal insulinNCT02131948
Regulation of Endogenous Glucose Production by Brain Insulin Action
A Phase 1 study testing Intranasal insulin in people with Insulin Resistance, Diabetes, 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, Diabetes
- What is being tested?
- Intranasal insulin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2013to Jul 2014
- Phase
- Phase 1
- 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 20-27.
- 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.
- Volunteers who have taken part in the study with the previously approved protocol will be eligible to participate in the amended study, if they provide their informed consent
Who cannot join
- Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years.
- 2. Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.
- 3. Any current or previous history of endocrine disease, dyslipidemia or malignancy 4. 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 5. Use of immunosuppressive agents at any time during the study 6. Allergy to any study medication 7. Pregnancy or breastfeeding 8. Heavy smoker 9. Prior nasoduodenal tube insertion under fluoroscopic guidance. 10. Fasting blood glucose > 6.0 mmol/l or known diabetes. 11. Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
- 12. Any nasal pathology likely to affect absorption of insulin or insertion of nasoduodenal tube.
- 13. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l 14. Current addiction to alcohol or substances of abuse as determined by the investigator.
- 15. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation 16. 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.
- 17. 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
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. We aim to test whether this is true in humans by giving insulin intranasally. It has previously been shown that a nasal spray can deliver insulin directly to the brain without affecting circulating insulin concentration.
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 UPC: 063636 802721, Item 10271) immediately prior to use. This device dispenses 0.1ml (10 IU) per puff. 4X0.1 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, Diabetes
- Being tested
- Intranasal insulin, Intranasal placebo
- Keywords
- Insulin resistance, Brain insulin action, Type 2 Diabetes
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal insulinDrug
Also called Humalog lispro 40 IU intranasally
Intranasal spray
Intranasal placeboDrug
Also called Diluent intranasally
Intranasal spray
| 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 posted6 May 2014 (estimated)
- Study startNov 2013
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin Resistance, DiabetesStudies 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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 8 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
- NCT02131948
- Sponsor's protocol ID
- REB 12-5032A
- Acronym
- Nasal insulin
- Status last verified
- Nov 2015
- First submitted
- 2 May 2014
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Endogenous Glucose Production by Brain Insulin Action
- ClinicalTrials.gov ID
- NCT02131948
- Acronym / sponsor ID
- Nasal insulin / REB 12-5032A
- Conditions
- Insulin Resistance, Diabetes
- Keywords
- Insulin resistance, Brain insulin action, Type 2 Diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 6 May 2014 (estimated)
- 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. We aim to test whether this is true in humans by giving insulin intranasally. It has previously been shown that a nasal spray can deliver insulin directly to the brain without affecting circulating insulin concentration.
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 UPC: 063636 802721, Item 10271) immediately prior to use. This device dispenses 0.1ml (10 IU) per puff. 4X0.1 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 (6 listed)
- Men and women, aged 18 to 60 years
- Body mass index 20-27.
- 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 (7 listed)
- Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years.
- 2. Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.
- 3. Any current or previous history of endocrine disease, dyslipidemia or malignancy 4. 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 5. Use of immunosuppressive agents at any time during the study 6. Allergy to any study medication 7. Pregnancy or breastfeeding 8. Heavy smoker 9. Prior nasoduodenal tube insertion under fluoroscopic guidance. 10. Fasting blood glucose > 6.0 mmol/l or known diabetes. 11. Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
- 12. Any nasal pathology likely to affect absorption of insulin or insertion of nasoduodenal tube.
- 13. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l 14. Current addiction to alcohol or substances of abuse as determined by the investigator.
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: Humalog lispro 40 IU intranasallyIntranasal spray | Drug | Intranasal insulin |
| Intranasal placeboAlso: Diluent intranasallyIntranasal spray | 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 2 Dec 2015.
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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 study testing Intranasal insulin in people with Insulin Resistance, Diabetes, 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 6 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 2 Dec 2015. 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 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.
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 2 Dec 2015.