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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

Tracking Information
First Submitted Date  ICMJE July 26, 2017
First Posted Date  ICMJE July 31, 2017
Last Update Posted Date March 20, 2020
Actual Study Start Date  ICMJE November 1, 2017
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
PostPrandial Blood Glucose [ Time Frame: Up to 4 hours following meal ]
Continuous glucose monitoring (CGM) using YSI will be used to measure blood glucose (mg/dl). Data will be collected for a maximum 4 hours following each meal.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
  • 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)).
  • 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)).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Improving Post-Prandial Blood Glucose Control With Afrezza During Closed-Loop Therapy
Official Title  ICMJE Improving Post-Prandial Blood Glucose Control With Afrezza During Closed-Loop Therapy
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Post-Prandial Hyperglycemia
  • Post-Prandial Hypoglycemia
Intervention  ICMJE
  • Device: DiAS
    Diabetes Assistant (DiAS) hybrid closed loop system.
  • Drug: Afrezza low dose
    Afrezza inhaled insulin low dose.
  • Drug: Afrezza high dose
    Afrezza inhaled insulin high dose.
Study Arms  ICMJE
  • 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).
    Interventions:
    • Device: DiAS
    • Drug: Afrezza 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).
    Interventions:
    • Device: DiAS
    • Drug: Afrezza 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).
    Intervention: Device: DiAS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 26, 2017)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2022
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lori Carria 203-737-3595 lori.carria@yale.edu
Contact: Kristen Kramer 203-737-3595 kristen.kraemer@yale.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03234491
Other Study ID Numbers  ICMJE 2000020715
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eda Cengiz, Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Yale University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP