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

Intranasal Insulin: A Novel Therapy for Hypoglycemia Unawareness in Type 1 Diabetes

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04028960

Enrollment

Registered

2019-07-23

Start date

2019-10-23

Completion date

2020-04-08

Last updated

2021-05-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type1diabetes

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

Interventions

DRUGRegular insulin (Humulin-R), intranasal route

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

DEVICESipNose 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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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)
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)
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
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)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Placebo, Then Humulin-R Insulin Participants first received a Placebo using the SipNose device twice daily for 14-20 days. After a washout period of 2 weeks, they received Humulin-R Insulin using the SipNose device twice daily for 14-20 days. 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.	2
Humulin-R Insulin, Then Placebo Participants first received Humilin-R Insulin using the SipNose device twice daily for 14-20 days. After a washout period of 2 weeks, they received a Placebo using the SipNose device twice daily for 14-20 days. 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. 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.	2
Total	4

Baseline characteristics

Characteristic	Placebo, Then Humulin-R Insulin	Humulin-R Insulin, Then Placebo	Total
Age, Continuous	64.5 years STANDARD_DEVIATION 3.5	40.5 years STANDARD_DEVIATION 6.4	52.5 years STANDARD_DEVIATION 14.5
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	2 Participants	4 Participants
Region of Enrollment United States	2 participants	2 participants	4 participants
Sex: Female, Male Female	2 Participants	0 Participants	2 Participants
Sex: Female, Male Male	0 Participants	2 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 4
other Total, other adverse events	3 / 4	4 / 4
serious Total, serious adverse events	0 / 4	0 / 4

Outcome results

Primary

Percentage of Time With Dangerous Hypoglycemia

Defined using percent time below range (\<54 mg/dL), from real-time continuous glucose monitoring (CGM)