Study Comparing Prandial Insulin Aspart vs. Technosphere Insulin in Patients With Type 1 Diabetes on Multiple Daily Injections: Investigator-Initiated A Real-life Pilot Study-STAT Study
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Technosphere insulin
Intervention description: This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. Patients who are randomized into the TI arm will be instructed to dose before the meals and take necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone visits). There will be a 4-week treatment comparison between TI and NL and 1-week of post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.
Intervention MeSH terms: Insulin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: diabetes; time in range; inhaled insulin; continuous glucose monitoring; type 1 diabetes; hypoglycemia; post prandial hypergylcemia

Summary:

      This is an investigator-initiated, prospective, randomized, multicenter, parallel,
      open-label, pilot clinical trial evaluating the efficacy of TI for PPBG, PPGE, and
      time-in-range on CGM download in patients with T1D. TI is an inhaled ultra-rapid-acting
      insulin, approved by the FDA for use in patients with diabetes. This is a pilot, real-life
      study where patients will continue their routine diabetes care and use post-meal correction
      dosages as deemed necessary for normalizing PPBG as per the protocol.

      This multi-center study will enroll 60 patients with T1D, A1c values between 6.5 to 10%. The
      patients will be randomized in 1:1 fashion to either TI or NL. Patients who are randomized
      into the NL arm will continue using their usual prandial insulin dose before meals. Patients
      who are randomized into the TI arm will be instructed to dose before the meals and take
      necessary corrections at 1- and 2-hours after meals to optimize PPBG (Table 1B). There will
      be a total of 7 study visits (screening visit, randomization visit, 2 clinic, and 3 phone
      visits). There will be a 4-week treatment comparison between TI and NL and 1-week of
      post-study follow up. (Phone visit; Figure-1). Standard lab tests (A1c, complete metabolic
      panel {CMP}, complete blood count {CBC}) will be performed at the screening visit.

      All patients will use real-time CGM (Dexcom G5®, San Diego, CA), which will be provided at
      the randomization visit for their day-to-day diabetes care. CGM data will be downloaded at
      every clinic visit on a secured computer. The data will be analyzed after the study for
      different primary and secondary end points. All patients will be allowed to keep the CGM
      after the study is over for their day-to-day diabetes care.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed informed consent before any study-related activities,

          2. Male or female aged 18-70 years,

          3. Type 1 diabetes mellitus (T1D) duration more than six months

          4. Treatment with multiple daily injections (MDI) for at least three months before
             screening visit; stable insulin dose for the last one month,

          5. No use of any oral anti-diabetics, any other form of insulin other than mentioned in
             the protocol, or any other type of injections such as glucagon-like-peptide-1 (GLP-1)
             analogs, pramlintide or insulin/GLP-1 analog combinations,

          6. A1c between 6.5 to 10%,

          7. Willingness to routinely collect at least two blood glucose measurements per day
             needed to calibrate the CGM. Beyond the calibrations, patients may use CGM for
             necessary action without having to confirm with fingersticks self-monitoring blood
             glucose (SMBG), as approved by the Food and Drug Administration (FDA),

          8. BMI ≤35 kg/m2,

          9. Ability and willingness to adhere to the protocol including clinical and phone visits
             and 4-week-long CGM wear,

         10. Using insulin glargine or insulin degludec as basal insulin,

         11. Able to use and understand CGM data,

         12. Willing to complete phone and clinic visits,

         13. Patients who eat three main meals in a day (breakfast, lunch, and dinner),

         14. Patients who use insulin-carb ratio for bolus,

         15. Ability to speak, read, and write English, and

         16. Patients prandial insulin need must be <18 units per meal

        Exclusion Criteria:

          1. Use of any other diabetic medication other than allowed in the protocol,

          2. Pregnant or intention to become pregnant during the study, or not using adequate birth
             control methods,

          3. Severe unexplained hypoglycemia requiring emergency treatment in the previous three
             months,

          4. Use of systemic or inhaled corticosteroids,

          5. History of hemoglobinopathies,

          6. Diagnosis of anemia,

          7. Post-renal transplantation, currently undergoing dialysis, creatinine >2.0 mg/dl or a
             calculated creatinine clearance of <50 mL/min,

          8. Advanced or unstable retinopathy needing laser procedure or vitrectomy,

          9. History of pancreatitis,

         10. Extensive skin changes/diseases that inhibit wearing a sensor on normal skin,

         11. Known allergy to adhesives,

         12. Known allergy to study medication,

         13. Participation in another investigational study protocol within 30 days before
             enrollment,

         14. Known chronic obstructive pulmonary disease, pulmonary hypertension, asthma, pulmonary
             fibrosis, or any chronic pulmonary infection, or any systemic disease that primarily
             affects the lungs. History of any pulmonary nodule will be excluded to participate in
             the study,

         15. Active smokers,

         16. Marijuana users,

         17. Insulin pump users,

         18. Using insulin detemir or NPH as basal insulin, and

         19. Any other condition, as determined by the investigator, which could make the subject
             unsuitable for the trial, impairs the subject's suitability for the trial, or impairs
             the validity of the informed consent -