Artificial Pancreas With Different Stress Assessments in the Outpatient Setting

• ClinicalTrials.gov Identifier: NCT04142229
• Recruitment Status: Recruiting
• First Posted: October 29, 2019
• Last Update Posted: October 29, 2019
• Sponsor: Sansum Diabetes Research Institute
• Collaborators: Mayo Clinic; Harvard University
• Information provided by (Responsible Party): Sansum Diabetes Research Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: iAPS; Other: Sensor-Augmented Pump	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 25, 2019
• Estimated Primary Completion Date: June 30, 2020
• Estimated Study Completion Date: June 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Automated Insulin Delivery; Participants will use the Automated Insulin Delivery (AID) iAPS system for 2 weeks in the outpatient setting, and come to the clinical center twice for supervised stress assessments.	Device: iAPS; The AID system (iAPS) is comprised of an insulin pump, a Dexcom G6 continuous glucose monitoring sensor, and a smart phone that contains the algorithm and communicates with the other devices.
Active Comparator: SAP/PLGS; Participants will use their home pump with a CGM sensor (sensor augmented pump) or in Predictive Low Glucose Suspend (PLGS) mode if their home pump supports this mode, for 2 weeks in the outpatient setting, and come to the clinical center twice for supervised stress assessments.	Other: Sensor-Augmented Pump; Subjects will use their home insulin pump and a Dexcom G6 continuous glucose monitoring sensor.

Outcome Measures

Primary Outcome Measures :

1. Time in target glucose range [ Time Frame: 4 weeks ]
   Time in target glucose range 70-180 mg/dL measured by CGM to determine safety and efficacy of the integrated system

Secondary Outcome Measures :

1. Change in glucose levels with stress induction [ Time Frame: 4 weeks ]
   Change in glucose levels with stress induction sessions (mg/dL)
2. Change in insulin requirements with stress induction [ Time Frame: 4 weeks ]
   Change in insulin requirements with stress induction sessions (units of insulin)
3. EDA stress detection [ Time Frame: 4 weeks ]
   Analysis of EDA to verify stress detection and correlation to glucose changes, both during the stress sessions and in the outpatient setting
4. Postprandial Time in Target Range [ Time Frame: 4 weeks ]
   Percent time within the target range of 70-180 mg/dl postprandial within 5 hours following meals
5. Glucose < 70 mg/dL [ Time Frame: 4 weeks ]
   Percent time GGM glucose < 70 mg/dL
6. Glucose < 54 mg/dL [ Time Frame: 4 weeks ]
   Percent time GGM glucose < 54 mg/dL
7. Glucose > 180 mg/dL [ Time Frame: 4 weeks ]
   Percent time GGM glucose > 180 mg/dL
8. Glucose > 250 mg/dL [ Time Frame: 4 weeks ]
   Percent time GGM glucose > 250 mg/dL
9. Serious adverse events (SAE) [ Time Frame: 4 weeks ]
   The total number of serious adverse events during the clinical trial
10. Serious adverse device events (SADE) [ Time Frame: 4 weeks ]
    The total number of serious adverse events related to the study device use during the clinical trial
11. Adverse device effects (ADE) [ Time Frame: 4 weeks ]
    The total number of adverse device effects (ADE) during the clinical trial
12. Unanticipated adverse device effects (UADE) [ Time Frame: 4 weeks ]
    The total number of unanticipated adverse device effects (UADE) during the clinical trial
13. Salivary cortisol assessment [ Time Frame: 4 weeks ]
    Salivary cortisol assessment (nmol/l) during psychologic and physiologic stress induction
14. Empatica device-based assessment of psychologic and physiologic stress [ Time Frame: 4 weeks ]
    EDA Measurement of psychologic and physiologic stress from the Empatica E4 Watch
15. Trier Social Stress Test (TSST) [ Time Frame: 4 weeks ]
    Trier Social Stress Test (TSST) score at end of each test induction
16. Socially evaluated cold-pressor test (SECPT) [ Time Frame: 4 weeks ]
    Socially evaluated cold-pressor test (SECPT) score at end of each test induction

Other Outcome Measures:

1. Closed-Loop Active Time [ Time Frame: 2 weeks ]
   Percent time (hours/day) of closed-loop use during the two weeks of iAPS use
2. Sensor Use Time [ Time Frame: 4 weeks ]
   Total hours of CGM sensor use time during both use of SAP/PLGS and when using the iAPS
3. Device Issues [ Time Frame: 4 weeks ]
   Total number of devices issues during the clinical trial
4. Total daily insulin use [ Time Frame: 4 weeks ]
   Total daily insulin use (units/day) during both use of SAP/PLGS and when using the iAPS
5. Total basal insulin use [ Time Frame: 4 weeks ]
   Total daily basal insulin use (units/day) during both use of SAP/PLGS and when using the iAPS
6. Total bolus insulin use [ Time Frame: 4 weeks ]
   Total daily bolus insulin use (units/day) during both use of SAP/PLGS and when using the iAPS
7. Questionnaire Score [ Time Frame: 2 weeks ]
   Questionnaire before and after AID use to assess technology acceptance, fear of hypoglycemia, diabetes associated distress (Likert Scale)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Molly Piper; 805-682-7640 ext 214; mpiper@sansum.org

Locations

United States, California

Sansum Diabetes Research Institute; Recruiting

Santa Barbara, California, United States, 93105

Contact: Molly Piper 805-682-7640 ext 214 mpiper@sansum.org

Principal Investigator: Jordan E Pinsker, MD

Sub-Investigator: Mei Mei Church, NP

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Shelly McCrady-Spitzer 507-255-0316 McCradySpitzer.Shelly@mayo.edu

Principal Investigator: Yogish Kudva, MBBS

Sponsors and Collaborators

Sansum Diabetes Research Institute

Mayo Clinic

Harvard University

Investigators

• Principal Investigator: Yogish Kudva, MBBS; Mayo Clinic
• Principal Investigator: Eyal Dassau, PhD; Harvard University
• Principal Investigator: Jordan Pinsker, MD; Sansum Diabetes Research Institute

More Information

• Responsible Party: Sansum Diabetes Research Institute
• ClinicalTrials.gov Identifier: NCT04142229
• Other Study ID Numbers: 19-006965
• First Posted: October 29, 2019
• Last Update Posted: October 29, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Sansum Diabetes Research Institute:

type 1 diabetes; automated insulin delivery; artificial pancreas; stress

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Insulin, Globin Zinc; Pancrelipase; Pancreatin; Hypoglycemic Agents; Physiological Effects of Drugs; Gastrointestinal Agents