Inhaled Insulin vs Rapid-acting Injections for Post-meal Glucose Control in Women With Gestational Diabetes

NCT ID: NCT06535789

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-31
• Study Completion Date: 2025-07-31

Brief Summary

Pregnant women aged 18-40 with gestational diabetes (GDM) will take part in this study. We want to see how two different insulin treatments affect their blood sugar after they eat. These women usually use a rapid-acting insulin analog (RAA) that's injected to control their blood sugar before and after meals. They will come to the clinic for two meal sessions. For the first meal, we will randomly decide if they will use the usual RAA insulin or a newer inhaled insulin called technosphere insulin (TI). They will use the other type of insulin for their second meal. After each meal, we will compare their blood sugar levels.

Detailed Description

Gestational diabetes mellitus (GDM) affects up to 25% of births globally, and its rates continue to rise each year. Pregnancy is a dynamic time marked by rapid changes in physiology, anatomy, and metabolism that support the growth and development of the fetus. This period can also be vulnerable, as expectant mothers may experience shifts in body perception, food preferences, and physical fitness, which can lead to decreased self-esteem, depression, and anxiety. A diagnosis of GDM often catches women by surprise and may bring feelings of guilt and anxiety about the potential effects on their baby's health. For pregnant individuals unable to meet specific glucose targets through diet and exercise alone, insulin is recommended as the primary treatment. However, transitioning to insulin injections can provoke fear, stress, and discomfort-both emotionally and physically-for many patients. Consequently, some pregnant women opt for oral anti-diabetic medications like metformin or glyburide due to their apprehension about using insulin injections. Both of these drugs pass through the placenta and raise safety concerns, making them secondary choices according to the American Diabetes Association (ADA) and the American College of Obstetricians and Gynecologists (ACOG).

While GDM is typically managed with injectable insulin, inhalable insulin offers a potential alternative. Technosphere® Insulin inhalation powder (TI) is an ultra-rapid-acting insulin administered via oral inhalation using a breath-powered inhaler. It provides an alternative to injectable insulin for prandial glucose control. It consists of recombinant human insulin adsorbed onto fumaryl diketopiperazine (FDKP), a proprietary excipient that, at acidic pH, self-assembles into particles, and polysorbate 80. TI particles have a median diameter of approximately 2 to 2.5 μm, a size appropriate for inhalation into the lung. Following inhalation, Afrezza particles dissolve immediately at the physiologic pH of the lung, and insulin and FDKP are absorbed systemically. After administration of TI in adults, the maximum serum insulin concentration occurs in approximately 12 to 15 minutes (versus 45 to 60 minutes for RAA via subcutaneous route) and returns to near baseline levels in approximately 180 minutes (versus about 5 hours for RAA).

The United States Food and Drug Administration (FDA) approved TI Inhalation Powder and the Gen2 Inhaler (a dry powder device) as Afrezza® to improve blood sugar control in adults aged 18 years and older with diabetes on June 27, 2014. Inhaled TI has proven safe and effective in reducing postprandial (after-meal) hyperglycemia in individuals with Type 1 and Type 2 diabetes. It's important to note that TI units are not equivalent to injectable insulin units; TI's bioequivalent dose has been found to be about twice that of injectable rapid-acting insulin when prescribed for diabetes management.

All insulins, including TI, have a similar label wording with respect to use in pregnancy indicating that studies have not shown an association of insulin and birth defects and that there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy. Insulin, whether subcutaneously administered or inhaled, has not been demonstrated to cross the placenta secondary to its large molecular weight. TI's inert excipient FDKP is not metabolized and is fully excreted from the body with the majority in urine and some in the feces (i.e. for the amount swallowed). Animal studies using subcutaneous administration of carrier particles at 21 times human dosing demonstrated no adverse fertility, teratogenicity, or other developmental outcomes (described in Afrezza label).

TI's optimal dosing, efficacy and risk for hypoglycemia in pregnancy is unknown. Outside of pregnancy, TI has been shown to cause less hypoglycemia than RAA insulin. The dose conversions of TI from RAA therapy have not been characterized in pregnancy to effectively administer across gestation with the dynamic metabolic changes, although insulin resistance is high in the 3rd trimester and dosing is expected to be at least as high as in patients with T2D (~2X SQ insulin dosing).

The goal of this investigator-initiated randomized crossover trial is to assess the efficacy of TI in lowering PP glycemia and the frequency of hypoglycemia compared with subcutaneous RAA insulin among pregnant individuals with GDM.

Conditions

Diabetes, Gestational; Pregnancy Complications; Glucose Metabolism Disorders; Glucose Intolerance During Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

technosphere insulin (TI)

All participants will ingest one standardized meal using technosphere insulin to manage their blood glucose

Group Type: EXPERIMENTAL

Inhaled Technosphere Insulin

Intervention Type: DRUG

Patients will receive TI (Afrezza) to be compared to RAA following a breakfast meal

Rapid-acting insulin analog

All participants will ingest one standardized meal using their prescribed rapid-acting insulin analog (RAA) to manage their blood glucose

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Inhaled Technosphere Insulin

Patients will receive TI (Afrezza) to be compared to RAA following a breakfast meal

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Ability to provide informed consent for study participation

2. Age ≥18 years and <41 years old

3. Singleton pregnancy at 24-34 weeks gestation

4. Diagnosis of GDM via standard 1-step or 2-step criteria

5. Treated with an insulin regimen that includes a RAA bolus of any type for breakfast, with a dose <20 units

6. Pre-pregnancy or first trimester body mass index (BMI) 25-45

7. Investigator believes that the protocol can be safely conducted by the participant

8. Able to read and speak English

Exclusion Criteria

1. Type 1 diabetes or type 2 diabetes

2. HbA1c ≥ 6.5%, FBG ≥125 mg/dl or 2-hr glucose ≥200 mg/dL on 75g OGTT, or random plasma glucose ≥200 mg/dL (consistent with pre-existing diabetes and not GDM diagnosis)

3. Current use of any non-insulin glucose lowering medication

4. Using TI (Afrezza), regular insulin, or ≥20 RAA units at breakfast (NPH is permissible)

5. Peak expiratory flow <80% predicted as measured by peak flow meter

6. Recent history of asthma (defined as using any medications to treat asthma within the last year), 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

7. Smoking (includes cigarettes, cigars, pipes, and/or vaping devices) within 90 days prior to screening

8. History or current diagnosis of lung cancer

9. Current or anticipated use of oral, inhaled or injectable glucocorticoids during the time period of the trial (topical glucocorticoid use is acceptable)

10. Renal or hepatic impairment that in the investigator's judgment poses a safety risk for the study participant

11. Recurrent Level 2 (blood glucose <54 mg/dL) or Level 3 severe hypoglycemia events

12. Current use of non-cardio-selective beta blockers

13. Being a member of the study team, having a direct supervisor at place of employment who is also 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 clinical trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mannkind Corporation

INDUSTRY

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amy Valent, DO

Role: STUDY_CHAIR

Oregon Health and Science University

Locations

Sansum Diabetes Research Institute

Santa Barbara, California, United States

Site Status: RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status: RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status: RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Katrina Ruedy, MSPH

Role: CONTACT

kruedy@jaeb.org

813-975-8690

Jennifer Gurley

Role: CONTACT

jgurley@jaeb.org

Facility Contacts

Sarintha Bell

Role: primary

sbell@sansum.org

805-682-7640

Jocelyn Phipers, RN

Role: primary

Jocelyn.Phipers@CUANSCHUTZ.EDU

303-724-7807

Denisa Tamarez

Role: primary

Denisa.tamarez@mssm.edu

212-241-9089

Monica Rincon

Role: primary

rincon@ohsu.edu

503-494-8748

Elizabeth Norton

Role: primary

Elizabeth.norton@pennmedicine.upenn.edu

800-789-7366

Other Identifiers

INHALE-GDM

Identifier Type: -

Identifier Source: org_study_id