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

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ClinicalTrials.gov Identifier: NCT04028960
Recruitment Status : Terminated (Funding was rescinded)
First Posted : July 23, 2019
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Sponsor:
Collaborators:
International Diabetes Center at Park Nicollet
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Type1diabetes Drug: Regular insulin (Humulin-R), intranasal route Device: SipNose intranasal device Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Intranasal Insulin: A Novel Therapy for Hypoglycemia Unawareness in Type 1 Diabetes
Actual Study Start Date : October 23, 2019
Actual Primary Completion Date : April 8, 2020
Actual Study Completion Date : April 8, 2020

Resource links provided by the National Library of Medicine


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
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.

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.




Primary Outcome Measures :
  1. Percentage of Time With Dangerous Hypoglycemia [ Time Frame: 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 :
  1. Percent of Time With Blood Glucose 70-180 mg/dL [ Time Frame: Two 14-20 day treatment periods ]
    Defined using percent of Blood Glucose 70-180 mg/dL from real-time continuous glucose monitoring (CGM)

  2. Percentage of Time With Blood Glucose <70 mg/dL [ Time Frame: Two 14-20 day treatment periods ]
    Defined using percent of Blood Glucose <70 mg/dL from real-time continuous glucose monitoring (CGM)

  3. Percentage of Time Blood Glucose >180 mg/dL [ Time Frame: Two 14-20 day treatment periods ]
    Percentage of time Blood Glucose >180 mg/dL from real-time continuous glucose monitoring (CGM)

  4. Percentage of Time With Blood Glucose >250 mg/dL [ Time Frame: Two 14-20 day treatment periods ]
    Percentage of time with Blood Glucose >250 mg/dL from real-time continuous glucose monitoring (CGM)

  5. Percentage of Time Participant Had Active Sensor Wear [ Time Frame: Two 14-20 day treatment periods ]
    Percentage of time Participant had Active Sensor Wear from real-time continuous glucose monitoring (CGM)

  6. Mean Glucose From the Study Participants [ Time Frame: Two 14-20 day treatment periods ]
    Mean Glucose from the Study Participants from real-time continuous glucose monitoring (CGM)

  7. Coefficient of Variation (%CV) of Blood Glucose Values From CGM Data [ Time Frame: 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.

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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028960


Locations
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United States, Minnesota
Health Partners Institute dba International Diabetes Center
Minneapolis, Minnesota, United States, 55416
Sponsors and Collaborators
HealthPartners Institute
International Diabetes Center at Park Nicollet
Juvenile Diabetes Research Foundation
Investigators
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Principal Investigator: Anders L Carlson, MD HealthPartners Institute
  Study Documents (Full-Text)

Documents provided by HealthPartners Institute:
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Responsible Party: HealthPartners Institute
ClinicalTrials.gov Identifier: NCT04028960    
Other Study ID Numbers: A16-716
First Posted: July 23, 2019    Key Record Dates
Results First Posted: May 18, 2021
Last Update Posted: May 18, 2021
Last Verified: May 2020

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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
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs