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

HealthPartners Institute

Status and phase

Terminated

Phase 2

Conditions

Type1diabetes

Treatments

Device: SipNose intranasal device

Drug: Regular insulin (Humulin-R), intranasal route

Study type

Interventional

Funder types

Other

Identifiers

NCT04028960

A16-716

Details and patient eligibility

About

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.

Full 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:

a. To assess non-inferiority of dangerous hypoglycemia with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia.
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.
Exploratory:
1. To describe changes in memory, attention and executive function with administration of intranasal insulin in T1D participants with intact awareness of hypoglycemia

Enrollment

4 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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.