IN Insulin in Type 1 Diabetes (T1D) Hypoglycemia Unawareness: Safety Only Phase

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.

Study Overview

• Status: Terminated
• Conditions: Type1diabetes
• Intervention / Treatment: Device: SipNose intranasal device; Drug: Regular insulin (Humulin-R), intranasal route

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:

1. Primary:

   a. To assess non-inferiority of dangerous hypoglycemia with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.

2. Secondary:

   1. To describe changes in overall glycemic control with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
   2. To describe changes in hypoglycemia awareness with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia
   3. To describe changes in safety endpoints with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.

3. Exploratory:

   1. To describe changes in memory, attention and executive function with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Health Partners Institute dba International Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
• 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

Exclusion Criteria:

• 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
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; No active drug	Device: SipNose intranasal device; 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.
Experimental: Humulin-R; Insulin	Device: SipNose intranasal device; 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.; Drug: Regular insulin (Humulin-R), intranasal route; Humulin-R insulin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time With Dangerous Hypoglycemia	Defined using percent time below range (<54 mg/dL), from real-time continuous glucose monitoring (CGM)	Two 14-20 day treatment periods

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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)	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)	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)	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)	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.	Two 14-20 day treatment periods
Glucose Management Indicator (GMI)	An approximate HbA1c based upon real-time continuous glucose monitoring (CGM) values	Two 14-20 day treatment periods

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Collaborators: Juvenile Diabetes Research Foundation; International Diabetes Center at Park Nicollet
• Investigators: Principal Investigator: Anders L Carlson, MD, HealthPartners Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2019
• Primary Completion (Actual): April 8, 2020
• Study Completion (Actual): April 8, 2020

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 19, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: A16-716

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes