Cystic Fibrosis-related Diabetes
Conditions
Keywords
cystic fibrosis, insulin, glucagon, continuous glucose monitor, bionic pancreas
Brief summary
The current study is designed to test the feasibility of the a wearable bionic pancreas system that automatically delivers insulin and glucagon can provide superior regulation of glycemia versus usual care for adults and children with cystic fibrosis related diabetes.
Interventions
DEVICEBionic Pancreas
Bionic pancreas system: The bionic pancreas is an autonomous, self-learning system that requires only the subject's weight for initialization, and then autonomously adapts insulin dosing to maintain glycemic control. The bionic pancreas uses continuous glucose monitoring as input to the controller. The bionic pancreas can be used in a bi-hormonal configuration, administering both insulin and glucagon as well as an insulin only setting.
OTHERUsual Care
Subjects will remain on home insulin regimen (either insulin pump or injectable insulin). Subjects in usual care will wear a study CGM even if in typical care does not include CGM use.
Sponsors
Beta Bionics, Inc.
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>/= 10 years and have had a diagnosis of cystic fibrosis related diabetes (CFRD) managed using either an insulin pump or multiple daily injections (MDI). * Mean continuous glucose monitoring (CGM) glucose \>/=125 mg/dl as determined by the participant's personal CGM 30-day download if CGM is used as part of their usual care. If the participant does not use CGM, hemoglobin A1c \>/= 6% within the last 6-months from available medical records will be required. * Minimum insulin requirement of \>/=0.1u/kg/day. To ensure that participants with a wide range of insulin requirements are included, participants whose insulin requirement is \<0.3u/kg/day will be limited to approximately 1/3 of the enrolled \>/=18 year old adult cohort. * Willing to wear iLet infusion sets and one Dexcom CGM sensor and change sets at least every other day in the iLet arm * Assent will be obtained for patients \<18 of age
Exclusion criteria
* Diabetes from etiologies other than CFRD * Unable to provide informed consent (e.g. impaired cognition or judgment) * Unable to safely comply with study procedures and reporting requirements (e.g. impairment of vision or dexterity that prevents safe operation of the bionic pancreas, impaired memory, unable to speak and read English) * Current participation in another clinical trial that, in the judgment of the principal investigator, will compromise the results of this study or the safety of the participant * Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the next 3-months, or sexually active without use of contraception o Participants must use acceptable contraception for the two weeks prior to the study, throughout the study and for the two weeks following the study. * History of hypoglycemic seizures (grand-mal) or coma in the last year * 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. * Unable to avoid hydroxyurea for duration of study (interferes with accuracy of Dexcom G6 CGM) * Unable to avoid taking higher than the maximum dose of acetaminophen from all sources for the duration of the study (interferes with accuracy of Dexcom G6 CGM) * Adult: 1 g every 6 hours, up to 4 g every 24 hours * Pediatric: 75 mg/kg/day in up to 5 doses, not to exceed 4000 mg/day * Have started or stopped a cystic fibrosis transmembrane conductance regulator (CFTR) modulator in the past 4 weeks. * Established history of allergy or severe reaction to adhesive or tape that must be used in the study * History of eating disorder within the last 2 years, such as anorexia, bulimia, or diabulemia or omission of insulin to manipulate weight * Use of oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, DPP-4 inhibitors, SGLT-2 inhibitors) or non-insulin injectable (GLP-1 agonists, amylin) anti-diabetic medications * History of lung or liver transplant * Anticipated lung transplant (on transplant list) * No acute pulmonary exacerbation or hospitalizations within the past 4 weeks or treatment with IV antibiotics in the past 4 weeks. * Any factors that, in the opinion of the principal investigator would interfere with the safe completion of the study * History of severe liver disease, including cirrhosis or portal hypertension * Presence of a medical condition or use of a medication that, in the judgment of the investigator, could compromise the results of the study or the safety of the participant. Conditions to be considered by the investigator may include the following: * Current alcohol abuse (intake averaging \>3 drinks daily in last 30 days) or other substance abuse (use within the last 6 months of controlled substances other than marijuana without a prescription) * Unwilling or unable to refrain from drinking more than 2 drinks in an hour or more than 4 drinks in a day during the trial * 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 beta blockers will be allowed as long as the dose is stable and the participant does not meet the criteria for hypoglycemia unawareness while taking that stable dose, but use of benzodiazepines or narcotics, even if by prescription, may be excluded according to the judgment of the principal investigator) * Renal failure requiring dialysis * Any known history of coronary artery disease including, but not limited to, history of myocardial infarction, stress test showing ischemia, history of angina, or history of intervention such as coronary artery bypass grafting, percutaneous coronary intervention, or enzymatic lysis of a presumed coronary occlusion) * Congestive heart failure (established history of CHF, lower extremity edema, paroxysmal nocturnal dyspnea, or orthopnea) oHistory of TIA or stroke * Seizure disorder, history of any non-hypoglycemic seizure within the last two years, or ongoing treatment with anticonvulsants * History of intentional, inappropriate administration of insulin leading to severe hypoglycemia requiring treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time in Glucose Target Range (70-180 mg/dl) as Determined by Continuous Glucose Monitor (CGM) on Days 3-14 | Days 3-14 | Percentage of time spent with CGM glucose values between 70 and 180 mg/dl |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean CGM Glucose | Days 3-14 | Average CGM glucose |
| Percentage of Time Spent With CGM Glucose < 70 mg/dl | Days 3-14 | Percent of time the participant spent with CGM glucose in this range |
| Percentage of Time Spent With CGM Glucose >180 mg/dL | Days 3-14 | The percent of time the participant spent with CGM glucose in this range |
| Percentage of Time Spent With CGM Glucose > 250mg/dL | Days 3-14 | The percent of time the participant spent with CGM glucose in this range |
| Standard Deviation | Days 3-14 | Standard deviation of participants' mean CGM glucose |
| Percentage of Time Spent With CGM Glucose: < 54 mg/dl | Days 3-14 | Percentage of time spent with CGM glucose in this range |
| Number of Episodes of Self-reported Symptomatic Hypoglycemia | Days 3-14 | Number of episodes subjects reported experiencing symptoms of low blood sugar (hypoglycemia) |
| Number of Subjects With Mean CGMG <154 mg/dl | Days 3-14 | Number of subjects who achieve a mean CGM glucose \< 154 mg/dl, which is the estimated average glucose for a hemoglobin A1c of 7% (ADA goal for therapy) |
| Number of Subjects With Percentage of Time < 54 mg/dl < 1% | Days 3-14 | Number of subjects who have less than 1% percent of CGM glucose values \< 54 mg/dl |
| Number of Subjects With Percentage of Time < 54 mg/dl < 1% and Mean CGM Glucose < or Equal to 154 mg/dl | Days 3-14 | Number of subjects who have less than 1% percent of CGM glucose values \< 54 mg/dl and also have a mean CGM glucose that is less than or equal to 154 mg/dl |
| Number of Subjects With Time in Range (70-180 mg/dl) of 70% or Greater | Days 3-14 | Number of subjects who have 70% percent or more of their CGM glucose values between 70 and 180 mg/dl |
| Coefficient of Variation | Days 3-14 | Coefficient of variation of CGM glucose values |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between April 2021 and June 2022
Pre-assignment details
30 adults were consented and screened for study participation. Of these, 3 did not meet inclusion criteria, 3 declined to participate, and 2 were lost to follow-up prior to randomization. The remaining 22 subjects were randomized. 2 subjects were assigned to a study arm but withdrew prior to any study procedures. No baseline or outcome data were collected in these 2 subjects, and they were excluded from all analyses. The remaining 20 subjects completed the study and are included in the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care First, Then Insulin Only Bionic Pancreas Usual Care diabetes management: Patients will manage their diabetes using standard of care for diabetes as per their typical regimen including use of an insulin pump or injectable insulin. Usual care arm for 14 days. Patients will wear a continuous glucose monitor (CGM) during this arm
Usual Care: Subjects will remain on home insulin regimen (either insulin pump or injectable insulin). Subjects in usual care will wear a study CGM even if in typical care does not include CGM use.
After 14 days of Usual Care, participants then crossed over to the Insulin only bionic pancreas arm for anther 14 days.
Insulin Only Bionic Pancreas diabetes management, a wearable bionic pancreas system that automatically delivers insulin using a continuous glucose monitoring (CGM) device, for 14 days.
Bionic Pancreas: Bionic pancreas system: The bionic pancreas is an autonomous, self-learning system that requires only the subject's weight for initialization, and then autonomously adapts insulin dosing to maintain glycemic control. The bionic pancreas uses continuous glucose monitoring as input to the controller. The bionic pancreas can be used in a bi-hormonal configuration, administering both insulin and glucagon as well as an insulin only setting. | 10 |
| Insulin Only Bionic Pancreas First, Then Usual Care Insulin Only Bionic Pancreas diabetes management, a wearable bionic pancreas system that automatically delivers insulin using a continuous glucose monitoring (CGM) device, for 14 days.
Bionic Pancreas: Bionic pancreas system: The bionic pancreas is an autonomous, self-learning system that requires only the subject's weight for initialization, and then autonomously adapts insulin dosing to maintain glycemic control. The bionic pancreas uses continuous glucose monitoring as input to the controller. The bionic pancreas can be used in a bi-hormonal configuration, administering both insulin and glucagon as well as an insulin only setting.
After 14 days of the insulin only bionic pancreas, participants then crossed over to the usual care arm for another 14 days.
Usual Care diabetes management: Patients will manage their diabetes using standard of care for diabetes as per their typical regimen including use of an insulin pump or injectable insulin. Usual care arm for 14 days. Patients will wear a continuous glucose monitor (CGM) during this arm
Usual Care: Subjects will remain on home insulin regimen (either insulin pump or injectable insulin). Subjects in usual care will wear a study CGM even if in typical care does not include CGM use. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (14 Days) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Usual Care First, Then Insulin Only Bionic Pancreas | Insulin Only Bionic Pancreas First, Then Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 17 | 39 years STANDARD_DEVIATION 10 | 40 years STANDARD_DEVIATION 13 |
| Body Mass Index (BMI) | 23.6 kg/m^2 STANDARD_DEVIATION 3.2 | 23.8 kg/m^2 STANDARD_DEVIATION 4.9 | 23.7 kg/m^2 STANDARD_DEVIATION 3.5 |
| Continuous glucose monitor (CGM) Use | 8 Participants | 10 Participants | 18 Participants |
| Cystic fibrosis related diabetes (CFRD) duration | 13 years STANDARD_DEVIATION 9 | 17 years STANDARD_DEVIATION 10 | 15 years STANDARD_DEVIATION 10 |
| Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Use | 7 Participants | 10 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 10 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| HbA1c | 8.0 % of glycated hemoglobin STANDARD_DEVIATION 1.5 | 6.2 % of glycated hemoglobin STANDARD_DEVIATION 2.7 | 7.4 % of glycated hemoglobin STANDARD_DEVIATION 1.6 |
| Insulin Pump Use | 3 Participants | 7 Participants | 10 Participants |
| Insulin Total Daily Dose | 0.62 units/kg/day STANDARD_DEVIATION 0.26 | 0.46 units/kg/day STANDARD_DEVIATION 0.3 | 0.54 units/kg/day STANDARD_DEVIATION 0.29 |
| Mean CGM glucose | 173 mg/dL STANDARD_DEVIATION 35 | 163 mg/dL STANDARD_DEVIATION 25 | 167 mg/dL STANDARD_DEVIATION 29 |
| Multiple Daily Injection Use | 7 Participants | 3 Participants | 10 Participants |
| Pancreatic insufficiency | 10 Participants | 10 Participants | 20 Participants |
| Percent predicted forced expiratory volume in 1 second (FEV1) | 76 % of predicted STANDARD_DEVIATION 26 | 65 % of predicted STANDARD_DEVIATION 21 | 70 % of predicted STANDARD_DEVIATION 24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 10 Participants | 18 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 4 / 20 | 6 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Percentage of Time in Glucose Target Range (70-180 mg/dl) as Determined by Continuous Glucose Monitor (CGM) on Days 3-14
Percentage of time spent with CGM glucose values between 70 and 180 mg/dl
Time frame: Days 3-14
Population: This was a random-order cross-over design clinical trial. Each participant completed each study arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Percentage of Time in Glucose Target Range (70-180 mg/dl) as Determined by Continuous Glucose Monitor (CGM) on Days 3-14 | 63 percentage of time spent in target range | Standard Deviation 22 |
| Insulin Only Bionic Pancreas | Percentage of Time in Glucose Target Range (70-180 mg/dl) as Determined by Continuous Glucose Monitor (CGM) on Days 3-14 | 75 percentage of time spent in target range | Standard Deviation 11 |
p-value: 0.001paired 2-sided t-test
Secondary
Coefficient of Variation
Coefficient of variation of CGM glucose values
Time frame: Days 3-14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Coefficient of Variation | 35 percentage of variability | Standard Deviation 6 |
| Insulin Only Bionic Pancreas | Coefficient of Variation | 35 percentage of variability | Standard Deviation 6 |
p-value: 1Wilcoxon signed rank test
Secondary
Mean CGM Glucose
Average CGM glucose
Time frame: Days 3-14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Mean CGM Glucose | 171 mg/dL | Standard Deviation 45 |
| Insulin Only Bionic Pancreas | Mean CGM Glucose | 150 mg/dL | Standard Deviation 19 |
p-value: 0.04paired 2-sided t-test
Secondary
Number of Episodes of Self-reported Symptomatic Hypoglycemia
Number of episodes subjects reported experiencing symptoms of low blood sugar (hypoglycemia)
Time frame: Days 3-14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Number of Episodes of Self-reported Symptomatic Hypoglycemia | 0.4 Episodes |
| Insulin Only Bionic Pancreas | Number of Episodes of Self-reported Symptomatic Hypoglycemia | 0.7 Episodes |
p-value: 0.01Wilcoxon signed rank test
Secondary
Number of Subjects With Mean CGMG <154 mg/dl
Number of subjects who achieve a mean CGM glucose \< 154 mg/dl, which is the estimated average glucose for a hemoglobin A1c of 7% (ADA goal for therapy)
Time frame: Days 3-14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Subjects With Mean CGMG <154 mg/dl | 9 Participants |
| Insulin Only Bionic Pancreas | Number of Subjects With Mean CGMG <154 mg/dl | 12 Participants |
p-value: 0.08McNemar
Secondary
Number of Subjects With Percentage of Time < 54 mg/dl < 1%
Number of subjects who have less than 1% percent of CGM glucose values \< 54 mg/dl
Time frame: Days 3-14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Subjects With Percentage of Time < 54 mg/dl < 1% | 17 Participants |
| Insulin Only Bionic Pancreas | Number of Subjects With Percentage of Time < 54 mg/dl < 1% | 16 Participants |
p-value: 0.56McNemar
Secondary
Number of Subjects With Percentage of Time < 54 mg/dl < 1% and Mean CGM Glucose < or Equal to 154 mg/dl
Number of subjects who have less than 1% percent of CGM glucose values \< 54 mg/dl and also have a mean CGM glucose that is less than or equal to 154 mg/dl
Time frame: Days 3-14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Subjects With Percentage of Time < 54 mg/dl < 1% and Mean CGM Glucose < or Equal to 154 mg/dl | 7 Participants |
| Insulin Only Bionic Pancreas | Number of Subjects With Percentage of Time < 54 mg/dl < 1% and Mean CGM Glucose < or Equal to 154 mg/dl | 8 Participants |
p-value: 0.56McNemar
Secondary
Number of Subjects With Time in Range (70-180 mg/dl) of 70% or Greater
Number of subjects who have 70% percent or more of their CGM glucose values between 70 and 180 mg/dl
Time frame: Days 3-14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Subjects With Time in Range (70-180 mg/dl) of 70% or Greater | 9 Participants |
| Insulin Only Bionic Pancreas | Number of Subjects With Time in Range (70-180 mg/dl) of 70% or Greater | 11 Participants |
p-value: 0.15McNemar
Secondary
Percentage of Time Spent With CGM Glucose >180 mg/dL
The percent of time the participant spent with CGM glucose in this range
Time frame: Days 3-14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Percentage of Time Spent With CGM Glucose >180 mg/dL | 31 percentage of time |
| Insulin Only Bionic Pancreas | Percentage of Time Spent With CGM Glucose >180 mg/dL | 18 percentage of time |
p-value: 0.014Wilcoxon signed rank test
Secondary
Percentage of Time Spent With CGM Glucose > 250mg/dL
The percent of time the participant spent with CGM glucose in this range
Time frame: Days 3-14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Percentage of Time Spent With CGM Glucose > 250mg/dL | 10 percentage of time |
| Insulin Only Bionic Pancreas | Percentage of Time Spent With CGM Glucose > 250mg/dL | 3.9 percentage of time |
p-value: 0.014Wilcoxon signed rank test
Secondary
Percentage of Time Spent With CGM Glucose: < 54 mg/dl
Percentage of time spent with CGM glucose in this range
Time frame: Days 3-14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Percentage of Time Spent With CGM Glucose: < 54 mg/dl | 0.36 percentage of time spent <54mg/dL |
| Insulin Only Bionic Pancreas | Percentage of Time Spent With CGM Glucose: < 54 mg/dl | 0.27 percentage of time spent <54mg/dL |
p-value: 1Wilcoxon signed rank test
Secondary
Percentage of Time Spent With CGM Glucose < 70 mg/dl
Percent of time the participant spent with CGM glucose in this range
Time frame: Days 3-14
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care | Percentage of Time Spent With CGM Glucose < 70 mg/dl | 1.5 percentage of time |
| Insulin Only Bionic Pancreas | Percentage of Time Spent With CGM Glucose < 70 mg/dl | 1.7 percentage of time |
p-value: 1Wicoxon signed rank test
Secondary
Standard Deviation
Standard deviation of participants' mean CGM glucose
Time frame: Days 3-14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Standard Deviation | 60 mg/dL | Standard Deviation 16 |
| Insulin Only Bionic Pancreas | Standard Deviation | 54 mg/dL | Standard Deviation 15 |
p-value: 0.14Wilcoxon signed rank test