IN Insulin in Type 1 Diabetes (T1D) Hypoglycemia Unawareness: Safety Only Phase
Condition: Type1diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
Intervention: Regular insulin (Humulin-R), intranasal route; SipNose intranasal device
Intervention description: Humulin-R insulin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetes.; 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 MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

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.