Type1diabetesPhase 2NCT04028960
IN Insulin in Type 1 Diabetes (T1D) Hypoglycemia Unawareness: Safety Only Phase
A Phase 2 study testing Regular insulin (Humulin-R), intranasal route and SipNose intranasal device in people with Type1diabetes, run by HealthPartners Institute at 1 site in United States.
Trial summary
The purpose of this study is to determine how Humulin-R regular insulin affects the body's ability to feel low blood sugar (hypoglycemia) when delivered intranasally compared to placebo in subjects with Type 1 Diabetes (T1D) with hypoglycemia awareness. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type1diabetes
- What is being tested?
- Regular insulin (Humulin-R), intranasal route and SipNose intranasal device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2019to 8 Apr 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult patients (age ≥18) with type 1 diabetes diagnosis and a duration of diabetes of at least 10 years
- Gold score <4
- HbA1c ≥6.5% within the last 3 months or at screen visit
- Stable insulin regimen (MDI or insulin pump) for at least 3 months, as deemed stable by principal investigator
- Depression/anxiety medications stable for at least 3 months
- Ability and willingness to wear CGM continuously during study participation
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- Participants must use their own smartphone, and have the ability and willingness to use CGM smartphone applications compatible with their smartphone
- Ability and willingness to check self-monitoring of blood glucose (SMBG) using own supplies, as instructed by study staff
- Ability and willingness to document when having symptoms of hypoglycemia in the CGM smartphone app or in a diary
- Willing to operate insulin pump without threshold suspend feature or hybrid closed-loop, if applicable
- Proficient in speaking, reading and understanding English in order to complete surveys and testing of cognitive function
- Women of child-bearing age must agree to procure and use contraception throughout the study
Who cannot join
- Pregnancy or planning pregnancy
- eGFR ≤ 30 mL/min per 1.73 m2, if available from medical record
- Completed any other research study within 6 months of screening date
- Current or recent use within 3 months of an insulin delivery system that adjusts insulin in response to continuous glucose monitoring (CGM) data (such as an automated insulin delivery system like hybrid closed-loop insulin pump therapy)
- Known dementia or mild cognitive impairment diagnosis
- Diabetic ketoacidosis within the last 6 months
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- Use of non-insulin medications to treat diabetes
- Those planning to change diet or exercise regimen during the study
- History of trans-sphenoidal surgery or surgery to the upper part of the nasal cavity, chronic sinusitis, severe deviated septum, or difficulty with smell and/or taste
- Severe psychiatric illness
- Allergy to adhesives, insulin or any components of insulin product
- Subject cannot adequately demonstrate ability to use and deploy the devices as determined by investigator
- Evidence of suicidality using the Columbia-Suicide Severity Rating Scale (C-SSRS)
- Subject has history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, condition known to affect absorption, distribution, metabolism, or excretion of drugs such as any hepatic, renal or gastrointestinal disease or any other clinically relevant abnormality or illness that inclusion would pose a safety risk to the subject as determined by investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
Health Partners Institute dba International Diabetes Center
Minneapolis, Minnesota, 55416
About this study
Official title: Intranasal Insulin: A Novel Therapy for Hypoglycemia Unawareness in Type 1 Diabetes
The purpose of this study is to determine how Humulin-R regular insulin affects the body's ability to feel low blood sugar (hypoglycemia) when delivered intranasally compared to placebo in subjects with Type 1 Diabetes (T1D) with hypoglycemia awareness. The study will use continuous glucose monitoring (CGM) to collect this information. The study drug or placebo will be administered using an intranasal device.
Read the detailed description
Hypoglycemia occurs with high frequency among patients with T1D. With repeated episodes of hypoglycemia, the counter-regulatory pathways to restore normal glucose are blunted, and patients can become unaware of the hypoglycemia. It is estimated that 40% of patients with T1D have hypoglycemia unawareness.
The study has the following objectives:
- Primary:
- To assess non-inferiority of dangerous hypoglycemia with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.
- Secondary:
- To describe changes in overall glycemic control with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
- To describe changes in hypoglycemia awareness with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
- To describe changes in safety endpoints with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.
- Exploratory:
- To describe changes in memory, attention and executive function with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
- Conditions
- Type1diabetes
- Being tested
- Regular insulin (Humulin-R), intranasal route, SipNose intranasal device
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regular insulin (Humulin-R), intranasal routeDrug
Humulin-R insulin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetes.
SipNose intranasal deviceDevice
The SipNose device is an aerosol nasal delivery platform that uses pressurized delivery through the discharge of compressed air, resulting in an aerosol that delivers the drug in a narrow plume geometry, which targets the olfactory epithelium in the upper nasal cavity. From the olfactory epithelium, therapeutics rapidly reach the central nervous system, traveling extracellularly along the olfactory nerves. The device is not currently commercially available, but numerous studies have demonstrated its ability to intranasally deliver radiolabeled and therapeutic compounds to the brain.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | No active drug Receives: Device: SipNose intranasal device |
| Humulin-R | Experimental | Insulin Receives: Drug: Regular insulin (Humulin-R), intranasal route; Device: SipNose intranasal device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Time With Dangerous Hypoglycemia
Defined using percent time below range (<54 mg/dL), from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Secondary outcomes (8)
Percent of Time With Blood Glucose 70-180 mg/dL
Defined using percent of Blood Glucose 70-180 mg/dL from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Percentage of Time With Blood Glucose <70 mg/dL
Defined using percent of Blood Glucose <70 mg/dL from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Percentage of Time Blood Glucose >180 mg/dL
Percentage of time Blood Glucose >180 mg/dL from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Percentage of Time With Blood Glucose >250 mg/dL
Percentage of time with Blood Glucose >250 mg/dL from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Percentage of Time Participant Had Active Sensor Wear
Percentage of time Participant had Active Sensor Wear from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Mean Glucose From the Study Participants
Mean Glucose from the Study Participants from real-time continuous glucose monitoring (CGM)
Measured: Two 14-20 day treatment periods
Coefficient of Variation (%CV) of Blood Glucose Values From CGM Data
The Coefficient of variation was calculated by dividing the standard deviation of blood glucose values by the mean of the blood glucose values based on data from the corresponding CGM readings.
Measured: Two 14-20 day treatment periods
Glucose Management Indicator (GMI)
An approximate HbA1c based upon real-time continuous glucose monitoring (CGM) values
Measured: Two 14-20 day treatment periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start23 Oct 2019
- Primary completion8 Apr 2020
- Study completion8 Apr 2020
Why it stopped: Funding was rescinded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- HealthPartners Institute
- Sponsor type
- University, hospital or other
- Collaborators
- International Diabetes Center at Park Nicollet, Juvenile Diabetes Research Foundation
- Responsible party
- Sponsor
- Investigators
- Anders L Carlson, MD, Principal investigator, HealthPartners Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04028960
- Sponsor's protocol ID
- A16-716
- Status last verified
- May 2020
- First submitted
- 19 Jul 2019
- Last updated
- 18 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Insulin: A Novel Therapy for Hypoglycemia Unawareness in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04028960
- Acronym / sponsor ID
- A16-716
- Conditions
- Type1diabetes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding was rescinded
- Enrolment
- 4 participants (actual)
- Lead sponsor
- HealthPartners InstituteUniversity, hospital or other
- Collaborators
- International Diabetes Center at Park Nicollet, Juvenile Diabetes Research Foundation
- Study start
- 23 Oct 2019 (actual)
- Primary completion
- 8 Apr 2020 (actual)
- Study completion
- 8 Apr 2020 (actual)
- First posted
- 23 Jul 2019 (actual)
- Results
- Posted 18 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine how Humulin-R regular insulin affects the body's ability to feel low blood sugar (hypoglycemia) when delivered intranasally compared to placebo in subjects with Type 1 Diabetes (T1D) with hypoglycemia awareness. The study will use continuous glucose monitoring (CGM) to collect this information. The study drug or placebo will be administered using an intranasal device.
Detailed description
Hypoglycemia occurs with high frequency among patients with T1D. With repeated episodes of hypoglycemia, the counter-regulatory pathways to restore normal glucose are blunted, and patients can become unaware of the hypoglycemia. It is estimated that 40% of patients with T1D have hypoglycemia unawareness.
The study has the following objectives:
- Primary:
- To assess non-inferiority of dangerous hypoglycemia with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.
- Secondary:
- To describe changes in overall glycemic control with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
- To describe changes in hypoglycemia awareness with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
- To describe changes in safety endpoints with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.
- Exploratory:
- To describe changes in memory, attention and executive function with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Device: SipNose intranasal deviceNo active drug |
| Humulin-R | Experimental | Drug: Regular insulin (Humulin-R), intranasal route, Device: SipNose intranasal deviceInsulin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adult patients (age ≥18) with type 1 diabetes diagnosis and a duration of diabetes of at least 10 years
- Gold score <4
- HbA1c ≥6.5% within the last 3 months or at screen visit
- Stable insulin regimen (MDI or insulin pump) for at least 3 months, as deemed stable by principal investigator
- Depression/anxiety medications stable for at least 3 months
Key exclusion criteria (14 listed)
- Pregnancy or planning pregnancy
- eGFR ≤ 30 mL/min per 1.73 m2, if available from medical record
- Completed any other research study within 6 months of screening date
- Current or recent use within 3 months of an insulin delivery system that adjusts insulin in response to continuous glucose monitoring (CGM) data (such as an automated insulin delivery system like hybrid closed-loop insulin pump therapy)
- Known dementia or mild cognitive impairment diagnosis
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 |
|---|---|---|
| Regular insulin (Humulin-R), intranasal routeHumulin-R insulin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetes. | Drug | Humulin-R |
| SipNose intranasal deviceThe SipNose device is an aerosol nasal delivery platform that uses pressurized delivery through the discharge of compressed air, resulting in an aerosol that delivers the drug in a narrow plume geometry, which targets the olfactory epithelium in the upper nasal cavity. From the olfactory epithelium, therapeutics rapidly reach the central nervous system, traveling extracellularly along the olfactory nerves. The device is not currently commercially available, but numerous studies have demonstrated its ability to intranasally deliver radiolabeled and therapeutic compounds to the brain. | Device | Humulin-R, Placebo |
Primary outcome
Percentage of Time With Dangerous Hypoglycemia
Time frame: Two 14-20 day treatment periods
Defined using percent time below range (<54 mg/dL), from real-time continuous glucose monitoring (CGM)
8 secondary outcomes
Percent of Time With Blood Glucose 70-180 mg/dL
Time frame: Two 14-20 day treatment periods
Percentage of Time With Blood Glucose <70 mg/dL
Time frame: Two 14-20 day treatment periods
Percentage of Time Blood Glucose >180 mg/dL
Time frame: Two 14-20 day treatment periods
Percentage of Time With Blood Glucose >250 mg/dL
Time frame: Two 14-20 day treatment periods
Percentage of Time Participant Had Active Sensor Wear
Time frame: Two 14-20 day treatment periods
Mean Glucose From the Study Participants
Time frame: Two 14-20 day treatment periods
Coefficient of Variation (%CV) of Blood Glucose Values From CGM Data
Time frame: Two 14-20 day treatment periods
Glucose Management Indicator (GMI)
Time frame: Two 14-20 day treatment periods
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Anders L Carlson, MD principal investigator
HealthPartners Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regular insulin (Humulin-R), intranasal route and SipNose intranasal device in people with Type1diabetes, run by HealthPartners Institute at 1 site in United States.
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 12 inclusion and 14 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: stopped early, as of the sponsor's last update on 18 May 2021. 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 United States. 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 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?
Yes. Results are posted in the registry (first posted 18 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Time With Dangerous Hypoglycemia (time frame: Two 14-20 day treatment periods). 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 18 May 2021.