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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Technosphere insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent before any study-related activities, Male or female aged 18-70 years, Type 1 diabetes mellitus (T1D) duration more than six months Treatment with multiple daily injections (MDI) for at least three months before screening visit; stable insulin dose for the last one month, 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, A1c between 6.5 to 10%, 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), BMI ≤35 kg/m2, Ability and willingness to adhere to the protocol including clinical and phone visits and 4-week-long CGM wear, Using insulin glargine or insulin degludec as basal insulin, Able to use and understand CGM data, Willing to complete phone and clinic visits, Patients who eat three main meals in a day (breakfast, lunch, and dinner), Patients who use insulin-carb ratio for bolus, Ability to speak, read, and write English, and Patients prandial insulin need must be <18 units per meal Exclusion Criteria: Use of any other diabetic medication other than allowed in the protocol, Pregnant or intention to become pregnant during the study, or not using adequate birth control methods, Severe unexplained hypoglycemia requiring emergency treatment in the previous three months, Use of systemic or inhaled corticosteroids, History of hemoglobinopathies, Diagnosis of anemia, Post-renal transplantation, currently undergoing dialysis, creatinine >2.0 mg/dl or a calculated creatinine clearance of <50 mL/min, Advanced or unstable retinopathy needing laser procedure or vitrectomy, History of pancreatitis, Extensive skin changes/diseases that inhibit wearing a sensor on normal skin, Known allergy to adhesives, Known allergy to study medication, Participation in another investigational study protocol within 30 days before enrollment, 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, Active smokers, Marijuana users, Insulin pump users, Using insulin detemir or NPH as basal insulin, and 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 -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Technosphere insulin (TI, Afrezza) -Treatment arm<br>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 ( post prandial blood glucose) | Drug: Technosphere insulin<br>* 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.<br>|
| No Intervention: Insulin Aspart ( Novolog) -Control arm<br>Patients who are randomized into the NL arm will continue using their usual prandial insulin dose before meals. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Time in Range (%) (70-180 mg/dl) With TI on CGM | Difference between Time in range for TI group (treatment) and for Aspart group (control) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Post-prandial Glucose Excursion (mg/dl) (1-4 Hours After Meals) With TI | Difference in postprandial blood glucose between treatment and control group | 4 weeks | 
| Change in Glucose Variability (GV) (mg/dl) (Standard Deviation and/or Coefficient Variation) | Difference of glucose variability metrics between treatment and control groups | 4 weeks | 
| The Area Under the Curve Calculation (AUC) (Min*mg/dl) in the PPBG and PPGE, | Difference of area under curve between treatment and control groups. ( 0 to 4 hours duration) | 0, 1, 2, 3, 4 hours post-dose at 4 weeks | 
| Change in HbA1c (%) in One-month Treatment | Difference in HbA1c between treatment and control group | 4 weeks | 
| Change in Above the Target Time (%) (>180 mg/dl) on CGM | Difference of time above range between treatment and control group | 4 weeks | 
| Hypoglycemia Frequency (%) (Below the Target <70mg/dl) on CGM | Difference of hypoglycemia frequency between treatment and control groups. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, time in range, inhaled insulin, continuous glucose monitoring, type 1 diabetes, hypoglycemia, post prandial hypergylcemia