Improving Post-Prandial Blood Glucose Control With Afrezza During Closed-Loop Therapy

NCT03234491 | Completed Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 2000020715
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be conducted in two phases; an in-patient meal study phase (Phase I) and an outpatient home study (Phase II). The two phase study design is chosen to enhance safety by testing the Afrezza Closed-Loop (CL) system in controlled in-clinic setting under study staff supervision before it could be investigated at the outpatient home setting. Phase II will not begin without the establishment of safety in Phase I.

Conditions

Post-Prandial Hyperglycemia; Post-Prandial Hypoglycemia

Keywords

Diabetes; Insulin

Outcome Measures

Primary Outcomes (1)

• PostPrandial Blood Glucose

  Continuous glucose monitoring (CGM) using Yellow Springs Instrument (YSI) will be used to measure blood glucose (mg/dl). Data will be collected for a maximum 4 hours following each meal.

  Up to 4 hours following meal

Secondary Outcomes (2)

• Insulin Levels

  Up to 4 hours following meal

• Venous Glucose Levels

  Up to 4 hours following meal

Study Arms (3)

A-HCL low

ACTIVE COMPARATOR

Trial arms will entail (a) HCL with RAI analog (insulin lispro or aspart) pre-meal bolus (R-HCL visit), (b) ACL with pre-meal dose titrated down to the lower dose inhaled insulin (AHCL low visit), and (c) ACL with pre-meal dose titrated up to higher dose inhaled insulin (A-HCL high visit).

Device: DiAS; Drug: Afrezza low dose

A-HCL high

ACTIVE COMPARATOR

Trial arms will entail (a) HCL with RAI analog (insulin lispro or aspart) pre-meal bolus (R-HCL visit), (b) ACL with pre-meal dose titrated down to the lower dose inhaled insulin (AHCL low visit), and (c) ACL with pre-meal dose titrated up to higher dose inhaled insulin (A-HCL high visit).

Device: DiAS; Drug: Afrezza high dose

R-HCL

ACTIVE COMPARATOR

Trial arms will entail (a) HCL with RAI analog (insulin lispro or aspart) pre-meal bolus (R-HCL visit), (b) ACL with pre-meal dose titrated down to the lower dose inhaled insulin (AHCL low visit), and (c) ACL with pre-meal dose titrated up to higher dose inhaled insulin (A-HCL high visit).

Device: DiAS

Interventions

DiAS DEVICE

Diabetes Assistant (DiAS) hybrid closed loop system.

A-HCL high; A-HCL low; R-HCL

Afrezza low dose DRUG

Afrezza inhaled insulin low dose.

A-HCL low

Afrezza high dose DRUG

Afrezza inhaled insulin high dose.

A-HCL high

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Previously diagnosed with Type 1 Diabetes Mellitus, as determined by the judgment of the Principal Investigator, based on clinical presentation and as documented in the clinic record (formal antibody or genetic testing will not be required).
• Diabetes duration at least 1 year.
• Willing to have an intravenous (IV) line inserted for frequent blood sampling and infusion of glucose.
• Hemoglobin A1c (HbA1c) ≤10%
• Speak and understand English.

You may not qualify if:

• HbA1c \>10.0% at the time of screening
• Insulin pump naïve subjects and subjects with unstable insulin dosing parameters requiring daily adjustments in insulin sensitivity factor, insulin to carbohydrate ratio and basal rates other than the established temporary rates that are determined to manage specific conditions such as exercise.
• History of an episode of severe hypoglycemia or Diabetic Ketoacidosis (DKA) requiring inpatient management within six months prior to the screening visit and/or subjects with history of clinician diagnosed hypoglycemia unawareness.
• History of recurrent DKA defined as more than three episodes of admissions for DKA during the past 12 months.
• Subjects requiring an insulin total daily dose \<0.1u/kg/day and \>3u/kg/day.
• History of physician diagnosis of asthma or any other clinically important pulmonary disease, or use of any medications to treat such conditions within the last year
• Allergy or know hypersensitivity for Afrezza or to drugs with similar chemical structure
• Any disease or exposure to any medication which, in the judgment of the principal investigator, may impact glucose metabolism.
• FEV1 \<70% of NHANES III; Forced vital capacity (FVC) \< 70% of NHANES III predicted for children ≥8 years of age.
• Positive urine pregnancy test for female patients of childbearing, breast feeding, or intention to become pregnant.
• Smoking of tobacco or other substances.
• Subjects who discontinued smoking (including cigarettes, cigars, pipes) within the past 6 months.
• History of abnormal spirometry or chest X-ray suggestive of lung disease.
• History of respiratory tract malignancy.
• Any condition or medication that may result in pulmonary toxicity (e.g. current or previous chemotherapy or radiation therapy or history of or current use of amiodarone).

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale Diabetes Research Clinic

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• Galderisi A, Cohen N, Calhoun P, Kraemer K, Breton M, Weinzimer S, Cengiz E. Effect of Afrezza on Glucose Dynamics During HCL Treatment. Diabetes Care. 2020 Sep;43(9):2146-2152. doi: 10.2337/dc20-0091. Epub 2020 Jul 13.

  PMID: 32661108 DERIVED

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus; Insulin Resistance

Interventions

Insulin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 31, 2017
• Study Start: November 22, 2017
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: May 25, 2022

Record last verified: 2022-05

Locations

US (1)