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

Phase 2

Terminated

Conditions: Type1diabetes

Interventions: Device: SipNose intranasal device
Drug: Regular insulin (Humulin-R), intranasal route

Registration Number: NCT04028960

Lead Sponsor: HealthPartners Institute

Brief 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. 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:

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	SipNose intranasal device	No active drug
Humulin-R	Regular insulin (Humulin-R), intranasal route	Insulin
Humulin-R	SipNose intranasal device	Insulin

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percent of Time With Blood Glucose 70-180 mg/dL	Two 14-20 day treatment periods	Defined using percent of Blood Glucose 70-180 mg/dL from real-time continuous glucose monitoring (CGM)
Percentage of Time With Blood Glucose <70 mg/dL	Two 14-20 day treatment periods	Defined using percent of Blood Glucose \<70 mg/dL from real-time continuous glucose monitoring (CGM)
Percentage of Time Blood Glucose >180 mg/dL	Two 14-20 day treatment periods	Percentage of time Blood Glucose \>180 mg/dL from real-time continuous glucose monitoring (CGM)
Percentage of Time With Blood Glucose >250 mg/dL	Two 14-20 day treatment periods	Percentage of time with Blood Glucose \>250 mg/dL from real-time continuous glucose monitoring (CGM)
Percentage of Time Participant Had Active Sensor Wear	Two 14-20 day treatment periods	Percentage of time Participant had Active Sensor Wear from real-time continuous glucose monitoring (CGM)
Mean Glucose From the Study Participants	Two 14-20 day treatment periods	Mean Glucose from the Study Participants from real-time continuous glucose monitoring (CGM)
Coefficient of Variation (%CV) of Blood Glucose Values From CGM Data	Two 14-20 day treatment periods	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.
Glucose Management Indicator (GMI)	Two 14-20 day treatment periods	An approximate HbA1c based upon real-time continuous glucose monitoring (CGM) values