Clinical trial NCT04142229: Artificial Pancreas With Different Stress Assessments in the Outpatient Setting
Official title: A Randomized Crossover Comparison of Artificial Pancreas vs. Sensor Augmented Pump/Predictive Low Glucose Suspend With Different Stress Assessments in the Outpatient Setting for Patients With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: type 1 diabetes
automated insulin delivery
artificial pancreas
stress
Lead sponsor: Sansum Diabetes Research Institute
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: Harvard University
First posted: 2019-10-29
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Crossover Assignment
Primary purpose: TREATMENT

Brief summary: This feasibility study is a randomized crossover trial that will compare the efficacy and safety of an automated insulin delivery (AID) system in patients with type 1 diabetes using a Model Predictive Control (MPC) algorithm versus sensor augmented pump therapy (SAP)/Predictive Low Glucose Suspend (PLGS), and will include different stress induction and assessments over a 4 week period.

Detailed description: Eligible participants will be randomly assigned to one of two treatment arms: 1) AID for two weeks and SAP/PLGS for two weeks , or 2) SAP/PLGS for two weeks and AID for two weeks. During the 4-week trial, subjects will wear the Empatica E4 wristband every day to record electrodermal activity, accelerometer and heartrate data. Subjects will also complete logbooks to record activity and stress. During each two-week period, subjects will come to the clinical center twice for stress induction tests in a medically supervised setting.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year
* Using an insulin pump for at least 3 months at the time of screening. Insulin pump use includes use of automated features, to include predictive or threshold low-glucose suspend or hybrid closed-loop with or without a Dexcom sensor.
* Familiarity and use of a carbohydrate ratio for meal boluses.
* Age ≥18.0 years old
* HbA1c \< 10.5%, as performed by point of care or central laboratory testing. HbA1c will be assessed at the screening visit, or if already completed within 2 weeks of the screening visit, the prior lab value may be used in lieu of repeating this assessment.
* For females, not currently known to be pregnant. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study and up to one month afterwards. A negative serum or urine pregnancy test will be required for all females of child-bearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
* Willingness to switch home pump to PLGS or full manual mode if using hybrid - Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol.
* Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study.
* Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial.

Exclusion Criteria:

* Use of an unapproved closed-loop insulin delivery system within 2 weeks before screening or during the study is not allowed.
* Have a blood pressure at screening outside the range of 160 mmHg systolic blood pressure and/or greater than 100 mmHg for diastolic blood pressure (if repeated measurements are within this range, the patient may be included in the study)
* Have coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise despite medical management, or within the last 12 months before screening a history of myocardial infarction, percutaneous coronary intervention, enzymatic lysis of a presumed coronary occlusion, or coronary artery bypass grafting
* Concurrent use of Afrezza or any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas).
* Hemophilia or any other bleeding disorder
* A condition, which in the opinion of the investigator or designee, would put the participant or study at risk, to include:

  * Pregnancy, or planning pregnancy within 1 month of completing the clinical trial.
  * Allergy or hypersensitivity to hydrocortisone, or any component of the formulation
  * Presence of a known adrenal disorder
  * Systemic fungal infections
  * Active infection of any kind, or at risk of infection (susceptibility to infection) from known immunosuppression or underlying immunosuppressed condition
  * Idiopathic thrombocytopenia purpura (ITP)
  * Varicella
  * Glaucoma or other chronic ocular condition that could be adversely affected by steroids (e.g., cataracts, increased ocular pressure from other causes, exophthalmos)
  * Hypertension requiring treatment with one or more antihypertensive medications
  * Congestive heart failure
  * Current treatment for a seizure disorder
  * Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation, including subjects not able to read or write
  * Known coronary artery disease
  * Active gastroparesis
  * Cystic fibrosis
  * Uncontrolled thyroid disease (TSH undetectable or \> 10 mIU/L)
  * Known abuse of alcohol
  * A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol
  * Current use of a beta blocker medication
  * Laboratory results:

    * HbA1c \> 10.5%
    * Abnormal liver or renal function (Transaminase \>2 times the upper limit of normal, creatinine\> 1.5 mg/dL)
    * Labs drawn at screening visit or within three months prior to screening (for other purposes) will suffice for enrollment purposes
  * Subject has skin conditions that, in the determination of the investigator, would preclude wearing the study devices (infusion set and sensor), in the abdomen. Examples include but are not limited to: psoriasis, burns, scaring, eczema, tattoos, and significant hypertrophy at sites of device wear; any known allergy to medical adhesives.
  * Currently on long-term treatment using prednisone or other steroid
  * If subject had been on short term treatment of prednisone, defer enrollment until underlying condition and prednisone treatment have resolved.
  * Allergy to study drug, food or other study material.
  * Clinically significant physical examination, laboratory test, or vital sign abnormality.
  * Exposure to any investigational drug within 30 days.
  * History of malignancy within the 5 years before screening (other than basal cell carcinoma).
* Participation in another pharmaceutical or device trial at the time of enrollment or during the study
* 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

Primary outcomes:
measure: Time in target glucose range
timeFrame: 4 weeks
Secondary outcomes:
measure: Change in glucose levels with stress induction
timeFrame: 4 weeks
measure: Change in insulin requirements with stress induction
timeFrame: 4 weeks
measure: EDA stress detection
timeFrame: 4 weeks
measure: Postprandial Time in Target Range
timeFrame: 4 weeks
measure: Glucose < 70 mg/dL
timeFrame: 4 weeks
measure: Glucose < 54 mg/dL
timeFrame: 4 weeks
measure: Glucose > 180 mg/dL
timeFrame: 4 weeks
measure: Glucose > 250 mg/dL
timeFrame: 4 weeks
measure: Serious adverse events (SAE)
timeFrame: 4 weeks
measure: Serious adverse device events (SADE)
timeFrame: 4 weeks
measure: Adverse device effects (ADE)
timeFrame: 4 weeks
measure: Unanticipated adverse device effects (UADE)
timeFrame: 4 weeks
measure: Salivary cortisol assessment
timeFrame: 4 weeks
measure: Empatica device-based assessment of psychologic and physiologic stress
timeFrame: 4 weeks
measure: Trier Social Stress Test (TSST)
timeFrame: 4 weeks
measure: Socially evaluated cold-pressor test (SECPT)
timeFrame: 4 weeks
Other outcomes:
measure: Closed-Loop Active Time
timeFrame: 2 weeks
measure: Sensor Use Time
timeFrame: 4 weeks
measure: Device Issues
timeFrame: 4 weeks
measure: Total daily insulin use
timeFrame: 4 weeks
measure: Total basal insulin use
timeFrame: 4 weeks
measure: Total bolus insulin use
timeFrame: 4 weeks
measure: Questionnaire Score
timeFrame: 2 weeks
Locations:
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Yogish Kudva, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University
name: Eyal Dassau, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sansum Diabetes Research Institute
name: Jordan Pinsker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pinsker JE, Deshpande S, McCrady-Spitzer S, Church MM, Kaur RJ, Perez J, Desjardins D, Piper M, Reid C, Doyle FJ 3rd, Kudva YC, Dassau E. Use of the Interoperable Artificial Pancreas System for Type 1 Diabetes Management During Psychological Stress. J Diabetes Sci Technol. 2021 Jan;15(1):184-185. doi: 10.1177/1932296820948566. Epub 2020 Aug 12. No abstract available.
citation: Kaur RJ, Deshpande S, Pinsker JE, Gilliam WP, McCrady-Spitzer S, Zaniletti I, Desjardins D, Church MM, Doyle Iii FJ, Kremers WK, Dassau E, Kudva YC. Outpatient Randomized Crossover Automated Insulin Delivery Versus Conventional Therapy with Induced Stress Challenges. Diabetes Technol Ther. 2022 May;24(5):338-349. doi: 10.1089/dia.2021.0436. Epub 2022 Apr 25.