Inhaled Technosphere versus rapid-acting insulin for exercise-related low blood sugar in adults with type 1 diabetes using automated insulin delivery

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

This trial will test whether inhaled Technosphere insulin given at mealtime reduces exercise-related low blood sugar compared with usual rapid-acting insulin in adults 18–65 with type 1 diabetes who use Tandem Control‑IQ automated insulin pumps.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Jaeb Center for Health Research (Academic / other)
• Locations: 3 sites (Louisville, Kentucky and 2 other locations)
• Trial ID: NCT06880835 on ClinicalTrials.gov

What this trial studies

This is a randomized, three-period crossover trial enrolling about 30 adults with type 1 diabetes who use Tandem t:slim X2 or Mobi pumps with Control‑IQ. Each participant completes three supervised afternoon exercise sessions after a standardized lunch: (1) inhaled Technosphere insulin (TI) with the pump in sleep mode, (2) rapid-acting analogue (RAA) insulin with the pump in sleep mode, and (3) RAA insulin with the pump in standard mode transitioned to exercise mode one hour before exercise. Outcomes compare safety and efficacy for preventing exercise-induced hypoglycemia following a meal bolus, with session order randomized for each participant. Continuous glucose and insulin-pump data are collected during each visit to compare glucose responses across the three conditions.

Who should consider this trial

Good fit: Adults 18–65 with type 1 diabetes who have used a Tandem t:slim X2 or Tandem Mobi pump with Control‑IQ for at least 90 days, take insulin aspart or lispro, have total daily insulin 20–80 units, typically use ≤12 units for a 50 g lunch bolus, and are physically active (≥3 moderate/vigorous sessions per week) are ideal candidates.

Not a fit: People who do not use Control‑IQ Tandem pumps, have higher daily insulin needs, use other insulin types, are not regularly active, or have contraindications to inhaled insulin or supervised exercise may not benefit from the findings.

Why it matters

Potential benefit: If successful, inhaled Technosphere insulin could reduce the frequency or severity of low blood sugar during post-meal exercise and offer a faster, possibly safer bolus option than pump-delivered rapid-acting insulin.

How similar studies have performed: Inhaled Technosphere insulin has prior evidence for rapid prandial glucose control, but applying it specifically to prevent exercise-induced hypoglycemia is a relatively novel approach with limited direct data.

Eligibility criteria

Inclusion Criteria:

1. Ability to provide informed consent for study participation
2. Age ≥18 years to 65 years
3. Clinical diagnosis of T1D (per the Investigator)
4. Using Tandem t:slim X2 or Tandem Mobi insulin pump with Control-IQ for at least 90 days prior to screening visit
5. Using insulin aspart or insulin lispro in Tandem 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

Where this trial is running

Louisville, Kentucky and 2 other locations

• University of Louisville — Louisville, Kentucky, United States (Recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• University of Washington — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Michael R Rickels, MD, MA — University of Pennsylvania
• Study coordinator: Robin Gal, MSPH

Conditions Diabetes Mellitus, Type 1; Exercise; Technosphere Insulin; Automated Insulin Delivery