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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03234491
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : March 20, 2020
Sponsor:
Information provided by (Responsible Party):
Eda Cengiz, Yale University

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.

Condition or disease Intervention/treatment Phase
Post-Prandial Hyperglycemia Post-Prandial Hypoglycemia Device: DiAS Drug: Afrezza low dose Drug: Afrezza high dose Phase 1

Detailed Description:

There are 2 primary study aims that this research will address. The first study aim will be to determine whether use of Afrezza inhaled insulin with ultra-fast kinetics will improve the performance of a closed-loop (CL) system, both with respect to immediate post-prandial hyperglycemia and the subsequent late post-prandial hypoglycemia as compared to hybrid CL (HCL) with subcutaneous (SC) rapid-acting insulin (RAI) pre-meal bolus.

The second study aim will be to examine the efficiency and feasibility of Afrezza inhaled insulin as a pre-meal bolus and a missed meal correction bolus on mitigating post-prandial blood glucose control during outpatient CL therapy.

This study will test the hypothesis that Afrezza inhaled insulin given before a meal to mimic physiologic first phase insulin release will limit the magnitude and rate of rise of glucose levels following a meal and will achieve greater percent time spent within target blood glucose range as compared to conventional hybrid CL therapy without inhaled insulin both in the in-clinic research and outpatient real-life setting.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Improving Post-Prandial Blood Glucose Control With Afrezza During Closed-Loop Therapy
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : February 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Sugar

Arm Intervention/treatment
Active Comparator: A-HCL low
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
Diabetes Assistant (DiAS) hybrid closed loop system.

Drug: Afrezza low dose
Afrezza inhaled insulin low dose.

Active Comparator: A-HCL high
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
Diabetes Assistant (DiAS) hybrid closed loop system.

Drug: Afrezza high dose
Afrezza inhaled insulin high dose.

Active Comparator: R-HCL
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
Diabetes Assistant (DiAS) hybrid closed loop system.




Primary Outcome Measures :
  1. PostPrandial Blood Glucose [ Time Frame: Up to 4 hours following meal ]
    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.


Secondary Outcome Measures :
  1. Insulin Levels [ Time Frame: Up to 4 hours following meal ]
    Insulin levels will be monitored during the study. It will will be calculated and reported by each one of the three treatment groups with the appropriate metric (mean(SD) or median(IRQ)).

  2. Venous Glucose Levels [ Time Frame: Up to 4 hours following meal ]
    The changes in venous levels from t=0 to peak and the peaks will be calculated and reported by each one of the three treatment groups with the appropriate metric (mean(SD) or median(IRQ)).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The age inclusion criterion is 18-29 years for phase I and 18-50y for phase II
  • 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.

Exclusion Criteria:

  • 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).
  • Inability to perform study procedures including pulmonary function testing and Afrezza inhalation using the BluHale system.
  • Patients who take acetaminophen containing medications on a regular basis or anticipate taking during the study period and are unable and/or unwilling to substitute with a non-acetaminophen containing medication.
  • Use of a device that may pose electromagnetic compatibility issues and/or radiofrequency interference with the DexCom CGM (implantable cardioverter defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants).
  • Active gastroparesis requiring current medical therapy.
  • Known bleeding diathesis or dyscrasia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03234491


Contacts
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Contact: Lori Carria 203-737-3595 lori.carria@yale.edu
Contact: Kristen Kramer 203-737-3595 kristen.kraemer@yale.edu

Locations
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United States, Connecticut
Yale Diabetes Research Clinic Recruiting
New Haven, Connecticut, United States, 06511
Contact: Lori Carria    203-737-3595    lori.carria@yale.edu   
Contact: Kristen Kraemer       kristen.kraemer@yale.edu   
Sponsors and Collaborators
Yale University

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Responsible Party: Eda Cengiz, Associate Professor of Pediatrics (Endocrinology), Yale University
ClinicalTrials.gov Identifier: NCT03234491    
Other Study ID Numbers: 2000020715
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Eda Cengiz, Yale University:
Diabetes
Insulin
Additional relevant MeSH terms:
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Hypoglycemia
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs