Post-Prandial HyperglycemiaPhase 1NCT03234491
Improving Post-Prandial Blood Glucose Control With Afrezza During Closed-Loop Therapy
A Phase 1 study testing DiAS, Afrezza low dose and Afrezza high dose in people with Post-Prandial Hyperglycemia and Post-Prandial Hypoglycemia, run by Yale University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Post-Prandial Hyperglycemia, Post-Prandial Hypoglycemia
- What is being tested?
- DiAS, Afrezza low dose and Afrezza high dose
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Nov 2017to 22 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 20Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Diabetes Research Clinic
New Haven, Connecticut, 06511
About this study
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.
Read the 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.
- Being tested
- DiAS, Afrezza low dose, Afrezza high dose
- Keywords
- Diabetes, Insulin
- Medical subject headings
- Hypoglycemia, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiASDevice
Diabetes Assistant (DiAS) hybrid closed loop system.
Afrezza low doseDrug
Afrezza inhaled insulin low dose.
Afrezza high doseDrug
Afrezza inhaled insulin high dose.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: Device: DiAS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 4 hours following meal
Secondary outcomes (2)
Insulin Levels
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)).
Measured: Up to 4 hours following meal
Venous Glucose Levels
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)).
Measured: Up to 4 hours following meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start22 Nov 2017
- Primary completion22 Jul 2019
- Study completion22 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-Prandial HyperglycemiaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234491
- Sponsor's protocol ID
- 2000020715
- Status last verified
- May 2022
- First submitted
- 26 Jul 2017
- Last updated
- 25 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
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.
PubMed 32661108
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Post-Prandial Blood Glucose Control With Afrezza During Closed-Loop Therapy
- ClinicalTrials.gov ID
- NCT03234491
- Acronym / sponsor ID
- 2000020715
- Keywords
- Diabetes, Insulin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 22 Nov 2017 (actual)
- Primary completion
- 22 Jul 2019 (actual)
- Study completion
- 22 Jul 2019 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A-HCL low | Active comparator | Device: DiAS, Drug: Afrezza low doseTrial 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). |
| A-HCL high | Active comparator | Device: DiAS, Drug: Afrezza high doseTrial 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). |
| R-HCL | Active comparator | Device: DiASTrial 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). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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%
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiASDiabetes Assistant (DiAS) hybrid closed loop system. | Device | A-HCL high, A-HCL low, R-HCL |
| Afrezza low doseAfrezza inhaled insulin low dose. | Drug | A-HCL low |
| Afrezza high doseAfrezza inhaled insulin high dose. | Drug | A-HCL high |
Primary outcome
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.
2 secondary outcomes
Insulin Levels
Time frame: Up to 4 hours following meal
Venous Glucose Levels
Time frame: Up to 4 hours following meal
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2022.
- Derived from this study: PubMed 32661108Galderisi 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.
Related trials for Post-Prandial Hyperglycemia
Active, not recruiting
How Fig Polyphenols Affect Blood Sugar and Insulin Levels After Eating in Adults at Risk for Diabetes
Pre Diabetic
Enrolling by invitation
Development of Anti-Diabetic Nutraceuticals From Legume Seed Coats
Postprandial Hyperglycemia, Type 2 Diabetes
Active, not recruiting
Effect of a Sugar Replacement on Blood Glucose Levels in Healthy Adults
Postprandial Hyperglycemia, Hyperinsulinemia
Recruiting
Ultra-processed Food-reducing Intervention and Continuous Glucose Monitoring
Postprandial Glucose, Glucose Levels
Not yet recruiting
Effect of a Food Supplement on Glycemic Parameters in Patients With Impaired Glucose Metabolism
Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (Prediabetes)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DiAS, Afrezza low dose and Afrezza high dose in people with Post-Prandial Hyperglycemia and Post-Prandial Hypoglycemia, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PostPrandial Blood Glucose (time frame: Up to 4 hours following meal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03234491, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2022.