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

NCT ID: NCT04028960

Last Updated: 2021-05-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-23
• Study Completion Date: 2020-04-08

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

Conditions

Type1diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

No active drug

Group Type: PLACEBO_COMPARATOR

SipNose intranasal device

Intervention Type: 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.

Humulin-R

Insulin

Group Type: EXPERIMENTAL

Regular insulin (Humulin-R), intranasal route

Intervention Type: DRUG

Humulin-R insulin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetes.

SipNose intranasal device

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

International Diabetes Center at Park Nicollet

OTHER

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

HealthPartners Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anders L Carlson, MD

Role: PRINCIPAL_INVESTIGATOR

HealthPartners Institute

Locations

Health Partners Institute dba International Diabetes Center

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

A16-716

Identifier Type: -

Identifier Source: org_study_id