Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Insulin-Only Bionic Pancreas Bridging Study

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03565666
Recruitment Status : Completed
First Posted : June 21, 2018
Results First Posted : September 4, 2019
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Steven J. Russell, MD, PhD, Massachusetts General Hospital

Brief Summary:

The iLet is a closed-loop delivery system that can be used in insulin-only, bihormonal, or glucagon-only configurations. Previous studies have utilized a phone-based bionic pancreas. The iLet consists of a touchscreen-enabled, menu-driven user interface and an onboard microprocessor that provides a comprehensive and standalone platform, which allows the iLet to operate independently of smartphones or other devices and without the need for internet support during routine operation.

This is a multicenter study of adult participants with type 1 diabetes, who will manage their diabetes with the iLet bionic pancreas compared to usual care.


Condition or disease Intervention/treatment Phase
Type1 Diabetes Mellitus Device: iLet Bionic Pancreas insulin-only configuration with Humalog or Novolog Drug: iLet Bionic Pancreas insulin-only configuration with Fiasp Other: Usual care Phase 2 Phase 3

Detailed Description:

This study will serve as a transitional study, bridging to larger and longer outpatient pivotal studies using the insulin-only configuration of the bionic pancreas.

The Adult RCT Period will consist of a multi-center, three-period, random-order, cross-over, feasibility study in 36 adult participants ≥ 18 years old with T1D. Insulin therapy for each participant will be administered (i) using the iLet in the insulin-only configuration and the insulin analog that they use for their usual care (either Humalog or Novolog) for 7 days, (ii) in another period using the iLet in the insulin-only configuration with faster insulin aspart (Fiasp) for 7 days (iii) in a third period using the participant's own usual care (UC) for 7 days. All three experimental periods will be followed by round-the-clock, remote, telemetric monitoring for hyperglycemia (> 300 mg/dl for ≥ 90 minutes) and hypoglycemia (< 50 mg/dl for ≥ 15 minutes). Half the subjects enrolled were expected to manage their diabetes with MDI and the other half with insulin pumps in their UC. An implantable Eversense CGM will also be placed in half the study participants for a CGM comparison.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Insulin-Only Bionic Pancreas Bridging Study
Actual Study Start Date : July 9, 2018
Actual Primary Completion Date : November 19, 2018
Actual Study Completion Date : November 19, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Adult RCT: Usual care
Participants randomized to usual care first started the usual care arm (UC) managing their diabetes with either multiple daily injections or continuous subcutaneous insulin infusion (pump therapy) for 7 days. All subjects wore a Dexcom G5 continuous glucose monitor (CGM) and half of all subjects also were a senseonics CGM. The usual care period was followed by the other 2 arms according to each subject's randomization schedule
Other: Usual care
Usual care

Experimental: Adult RCT: closed-loop control with iLet Humalog or Novolog
Participants randomized to the iLet with humalog/novolog first started the insulin-only iLet arm using the insulin analog that they use for their usual care (either Humalog or Novolog). All subjects wore a Dexcom G5 CGM and half of all subjects also wore a Senseonics Eversense CGM. The iLet period was followed by the other 2 arms according to each subject's randomization schedule
Device: iLet Bionic Pancreas insulin-only configuration with Humalog or Novolog
iLet Bionic Pancreas insulin-only configuration with Humalog or Novolog

Experimental: Adult RCT: closed-loop control with iLet using Fiasp
Participants randomized to the iLet with Fiasp first started the insulin-only iLet arm using faster insulin aspart (Fiasp) in PumpCart, where the pharmacokinetic (PK) parameter for tmax used by the insulin-dosing algorithm was set to the same value as is used for Humalog and Novolog (65 minutes). All subjects wore a Dexcom G5 CGM and half of all subjects also wore a Senseonics Eversense CGM. The iLet period was followed by the other 2 arms according to each subject's randomization schedule
Drug: iLet Bionic Pancreas insulin-only configuration with Fiasp
iLet Bionic Pancreas insulin-only configuration with Fiasp (faster insulin aspart)




Primary Outcome Measures :
  1. Mean CGM Glucose [ Time Frame: Days 3-7 for the RCT Period ]
  2. Percentage of Time Where Glucose is Less Than 54 mg/dL [ Time Frame: Days 3-7 for the RCT Period ]

Other Outcome Measures:
  1. Episodes of Severe Hypoglycemia [ Time Frame: Days 3-7 for the RCT Period ]
    Pre-specified to report the total number of episodes summed across all participants

  2. Episodes of Diabetic Ketoacidosis (DKA) [ Time Frame: Days 3-7 for the RCT Period ]
    pre-specified to report the total number of episodes summed across all participants

  3. Percentage of Time Where Glucose is Less Than 70 mg/dL [ Time Frame: Days 3-7 for the RCT Period ]
  4. Percentage of Time in the Glucose Target Range of 70-180 mg/dl [ Time Frame: Days 3-7 for the RCT Period ]
  5. Percentage of Time Where Glucose is Greater Than 180 mg/dL [ Time Frame: Days 3-7 for the RCT Period ]
  6. Percentage of Time Where Glucose is Less Than 60 mg/dL [ Time Frame: Days 3-7 for the RCT Period ]
  7. Percentage of Time Where Glucose is Greater Than 250 mg/dL [ Time Frame: Days 3-7 for the RCT Period ]
  8. Percentage Time in the Glucose Target Range of 70-120mg/dL [ Time Frame: Days 3-7 for the RCT Period ]
  9. Mean Absolute Relative Difference Between Dexcom G5 CGM and Contour Next One Glucose Meter [ Time Frame: Days 3-7 for the RCT Period ]
    The MARD is calculated as the mean value of individual absolute relative differences (ARD). The ARD is calculated as follows: 100*(CGM-reference glucose)/reference glucose

  10. Mean Absolute Relative Difference Between Senseonics Eversense CGM and Contour Next One Glucose Meter [ Time Frame: Days 1-7 of the Adult RCT period ]
    The MARD is calculated as the mean value of individual absolute relative differences (ARD). The ARD is calculated as follows: 100*(CGM-reference glucose)/reference glucose



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Clinical diagnosis of type 1 diabetes for at least one year and using insulin for at least 1 year
  2. Diabetes managed using an insulin pump for ≥ 3 months or with multiple daily injections (approximately 1/2 of participants should use a pump and approximately 1/2 should use MDI)
  3. Age ≥18 years;

    • There is no upper age limit in the Adult RCT Period (instead the exclusion criteria are used to restrict the participants to those healthy enough to participate in the trial)

  4. HbA1c level <11.0%

    • A point of care or local lab measurement is used to assess eligibility for screening.

  5. At least 3 SMBG meter tests daily on average or use of a CGM and 2 or more SMBG meter tests daily on average by history
  6. For females, not currently known to be pregnant

    • If female, sexually active, and at risk for pregnancy, must agree to use a highly effective form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all women who are post-menarche and pre-menopause who are not surgically sterile. Participants who become pregnant will be discontinued from the study.

  7. An understanding of and willingness to follow the protocol and sign the informed consent and assent where applicable

Exclusion Criteria:

-The presence of any of the following is an exclusion for the study:

  1. Unable to provide informed consent (e.g. impaired cognition or judgment)
  2. Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the BP, impaired memory)
  3. Unable to speak and read English
  4. Currently using for the first time a real-time CGM for < 1 month (Individuals who have been using CGM for 1 or more months are eligible)
  5. Current use of non-FDA approved closed-loop or hybrid closed-loop insulin delivery system
  6. Current use of insulin glulisine (Apidra) as part of usual diabetes home regimen
  7. Current off-label use of faster-acting insulin aspart (Fiasp) in CSII therapy as part of usual diabetes home regimen
  8. Current participation in another diabetes-related clinical trial that, in the judgment of the principal investigator, will compromise the results of this study or the safety of the participant
  9. Pregnant (positive urine HCG), breast feeding, plan to become pregnant in the next 12 months, or sexually active and at risk for pregnancy without use of contraception
  10. Current alcohol abuse (intake averaging >4 drinks daily in last 30 days) or other substance abuse (use within the last 3 months of controlled substances other than marijuana without a prescription)
  11. Unwilling or unable or to avoid use of drugs that may dull the sensorium, reduce sensitivity to symptoms of hypoglycemia, or hinder decision making during the period of participation in the study (use of benzodiazepines or narcotics, even if by prescription, may be excluded according to the judgment of the principal investigator)
  12. Stage 4 renal failure (eGFR <30) or Stage 5 renal failure on dialysis (hemodialysis or peritoneal dialysis)
  13. History of cystic fibrosis, pancreatitis, or other pancreatic disease, including pancreatic tumor or insulinoma, or history of complete pancreatectomy
  14. Coronary artery disease that is not stable with medical management, including unstable angina, angina that prevents moderate exercise (e.g. exercise of intensity up to 6 METS) 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
  15. Abnormal EKG consistent with increased risk of malignant arrhythmia including, but not limited to, evidence of active ischemia, proximal LAD critical stenosis (Wellen's sign), or prolonged QT interval (> 440 ms). Other EKG findings, including stable Q waves, are not grounds for exclusion as long as the participant is not excluded according to other criteria. A reassuring evaluation by a cardiologist after an abnormal EKG finding may allow participation.

    • EKG is only required for participants ≥50 years old or with diabetes duration ≥20 years

  16. For participants < 50 years of age and < 20 years since diagnosis: History of prolonged QT interval, malignant arrhythmia, or congenital heart disease
  17. Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV
  18. History of TIA or stroke in the last 12 months
  19. Recent history of diabetic ketoacidosis (DKA) or severe hypoglycemia in the last 6 months. Severe hypoglycemia is defined as an event that required assistance of another person due to altered consciousness, and required another person to actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the participant was impaired cognitively to the point that he/she was unable to treat himself/herself, was unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure or coma.
  20. History of more than 1 episode of DKA requiring hospitalization in the last 2 years
  21. History of more than 1 episode of severe hypoglycemia in the last year.
  22. Untreated or inadequately treated mental illness (indicators would include symptoms such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the last year), or treatment with anti-psychotic medications that are known to affect glucose regulation.
  23. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference
  24. Unable or unwilling to completely avoid acetaminophen for duration of study
  25. Established history of allergy or severe reaction to adhesive or tape that must be used in the study
  26. History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight
  27. Current or planned use of SGLT2 inhibitors (prior use more than 3 months prior to enrollment is acceptable; SGLT2 inhibitors should not be initiated during the trial)
  28. If using GLP1, pramlintide, or metformin must be on a stable dose for 3 months prior to enrollment (these agents should not be initiated during the trial)
  29. Required use of 2 or more steroid bursts in the 6 months prior to the trial
  30. History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
  31. Any factors that, in the opinion of the site principal investigator or clinical protocol chair, would interfere with the safe completion of the study, including medical conditions that may require hospitalization during the trial

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): NCT03565666


Locations
Layout table for location information
United States, California
Stanford University
Palo Alto, California, United States, 94305
United States, Colorado
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80045
United States, Florida
Nemours Children's Specialty Care
Jacksonville, Florida, United States, 32207
Sponsors and Collaborators
Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Steven J. Russell, MD, PhD, Massachusetts General Hospital:
Study Protocol  [PDF] June 26, 2018
Statistical Analysis Plan  [PDF] September 21, 2018


Layout table for additonal information
Responsible Party: Steven J. Russell, MD, PhD, Clinical Study Director, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03565666     History of Changes
Other Study ID Numbers: 2018P000853
First Posted: June 21, 2018    Key Record Dates
Results First Posted: September 4, 2019
Last Update Posted: September 4, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified IPD will be published as online supplemental material to the main paper describing the results, as we have done for all of our previous bionic pancreas studies.

Layout table for additional information
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
Pediatric Postmarket Surveillance of a Device Product: No
Keywords provided by Steven J. Russell, MD, PhD, Massachusetts General Hospital:
bionic pancreas
closed loop
insulin
continuous glucose monitor
Additional relevant MeSH terms:
Layout table for 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
Insulin Aspart
Insulin Lispro
Insulin, Long-Acting
Insulin degludec, insulin aspart drug combination
Pancrelipase
Pancreatin
Hypoglycemic Agents
Physiological Effects of Drugs
Gastrointestinal Agents