Clinical trial NCT06880835: Effect of Inhaled Technosphere Insulin vs RAA Insulin on Exercise-Induced Hypoglycemia in Adults With T1D Using Automated Insulin Delivery
Official title: INHALE-AIDEx: A Randomized Crossover Trial Evaluating the Effect of Inhaled Technosphere Insulin (Afrezza®) vs Rapid Acting Analogue Insulin on Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes Using Automated Insulin Delivery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes Mellitus, Type 1
Exercise
Technosphere Insulin
Automated Insulin Delivery
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Mannkind Corporation
name: Tandem Diabetes Care, Inc.
name: The Leona M. and Harry B. Helmsley Charitable Trust
First posted: 2025-03-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This investigator-initiated study will enroll about 30 adults 18 to 60 years of age with type 1 diabetes (T1D) who are using the Tandem t:slim X2 insulin pump with Control-IQ or Control-IQ+ technology ("Control-IQ" which will refer to either Control-IQ or Control-IQ+). The study is being done to find out if inhaled insulin given for a meal is safer and better to use than a bolus of insulin through your pump when you exercise following a meal. Participants are asked to complete three study exercise visits in the clinic.

Detailed description: The study is a 3-period randomized crossover trial, each with a structured afternoon exercise session following a standard lunch meal. The 3 sessions are as follows: (1) TI for meal bolus with pump in sleep mode, (2) RAA for meal bolus with pump in sleep mode, and (3) RAA for meal bolus with pump in standard mode with transition to exercise mode one hour before start of exercise. The study is being done to compare the efficacy and safety of TI versus RAA given as bolus for meal prior to initiating aerobic exercise in adults ≥18 to ≤ 60 years of age with T1D using Control-IQ.

All participants will complete 3 exercise sessions, with the order determined through randomization.

Eligibility criteria: Inclusion Criteria:

1. Ability to provide informed consent for study participation
2. Age ≥18 years to 60 years
3. Clinical diagnosis of T1D (per the Investigator)
4. Using Tandem t:slim X2 insulin pump with Control-IQ for at least 90 days prior to screening visit
5. Using insulin aspart or insulin lispro in Tandem t:slim X2 insulin pump
6. Total daily insulin dose 20 to 80 units
7. Usual RAA insulin bolus for 50 gram carbohydrate lunch meal is ≤12 units
8. Physically active, with at least 3 moderate or vigorous exercise sessions ≥30 minutes per typical week self-reported by participant
9. No medical, psychiatric, or other conditions, or medications being taken that in the Investigator's judgement would be a safety concern for participation in the study
10. No electrocardiogram (ECG) abnormality that in the judgment of the investigator, which will take into consideration the usual exercise performed by the participant and their overall medical condition, increases the risk of exercise
11. Investigator believes that the participant can safely follow the protocol
12. Able to read and understand written and spoken English or Spanish

Exclusion Criteria:

1. Use of inhaled insulin within one week prior to screening visit
2. History of asthma, chronic obstructive pulmonary disease (COPD), or any other clinically important pulmonary disease (e.g., cystic fibrosis or bronchopulmonary dysplasia), or significant congenital or acquired cardiopulmonary disease as judged by the Investigator
3. Smoking (includes cigarettes, cigars, pipes, marijuana, and vaping devices) within 90 days prior to screening visit and no plans to smoke during the study
4. History or current diagnosis of lung cancer
5. Forced expiratory volume in 1 second (FEV1) measurement of \<70% of predicted Global Lung Function Initiative value
6. Pregnant or lactating, planning to become pregnant during the study, or is of childbearing potential and not on acceptable form of birth control (acceptable includes abstinence, condoms, oral/injectable contraceptives, IUD, or implant); childbearing potential means that menstruation has started, and the participant is not surgically sterile or greater than 12 months post-menopausal)

   • A pregnancy test is required for any person of childbearing potential.
7. An event of severe hypoglycemia, as judged by the Investigator, within the 90 days prior to screening visit
8. An episode of diabetic ketoacidosis (DKA) as defined in section 5.2 within the 90 days prior to screening visit
9. Any disease other than diabetes or current use (or anticipated use during the study) of any medication (e.g., beta blocker) that, in the judgment of the Investigator, may substantially impact glucose metabolism
10. Use of a non-insulin glucose-lowering medication (or weight-reduction medication with glucose-lowering effect) within 4 weeks prior to screening visit
11. Exposure to any investigational drug in the 90 days prior to the screening visit
12. Current or anticipated acute uses of oral, inhaled, or injectable glucocorticoids during the time period of the study (topical or intranasal glucocorticoid use is acceptable)
13. Current use of Hydroxyurea medication
14. Current or anticipated use of a low carbohydrate diet (\<50 grams/day) or low calorie diet (\<800 kcal/day) during the time period of the study
15. Current treatment for diabetic retinopathy
16. Known stage 4/5 chronic kidney disease or on dialysis
17. Having a direct supervisor at place of employment who is directly involved in conducting the clinical trial (as a study Investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the study

Primary outcomes:
measure: Blood glucose <70 mg/dL
timeFrame: 90 minutes
Secondary outcomes:
Other outcomes:
measure: Exploratory Efficacy Outcome: Change in blood glucose from exercise start to nadir glucose
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: Change in CGM glucose from exercise start to nadir glucose
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: Time in range 70-180 mg/dL
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: Time in tight range 70-140 mg/dL
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: Mean glucose
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: CGM glucose <54 mg/dL
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: CGM glucose <70 mg/dL
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: CGM glucose >250 mg/dL
timeFrame: 90 minutes
measure: Exploratory Efficacy Outcome: CGM glucose >300 mg/dL
timeFrame: 90 minutes
measure: Safety Outcome: Severe hypoglycemia events
timeFrame: From enrollment to last clinic visit (up to ~12 weeks)
measure: Safety Outcome: Blood glucose <54 mg/dL during clinic
timeFrame: 210 minutes
measure: Safety Outcome: Blood glucose <70 mg/dL during clinic
timeFrame: 210 minutes
measure: Safety Outcome: Adverse events related to exercise procedure
timeFrame: From enrollment to last clinic visit (up to ~12 weeks)
measure: Safety Outcome: Adverse events associated with technosphere insulin inhalation
timeFrame: From enrollment to last clinic visit (up to ~12 weeks)
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Pennsylvania
name: Michael R Rickels, MD, MA
role: PRINCIPAL_INVESTIGATOR
affiliation: York University
name: Michael Ridell, PhD
role: STUDY_CHAIR
References: