Reduction of Nocturnal Hypoglycemia and Hyperglycemia in the Home Using Predictive Algorithms
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Endocrine, Diabetes, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 15 - 45 |
| Updated: | 4/21/2016 |
| Start Date: | June 2015 |
| End Date: | March 2016 |
Reduction of Nocturnal Hypoglycemia and Hyperglycemia in the Home Using Predictive Algorithms, Pump Suspension, and Insulin Dosing
Objective: to gain experience with in-home use of a modified algorithm that will dose
insulin to minimize projected hyperglycemia overnight in addition to suspending the pump if
hypoglycemia is projected overnight and to obtain feasibility, safety, and initial efficacy
data.
Study Design: randomized controlled trial, with randomization on a night level within
subject.
Major Eligibility Criteria: clinical diagnosis of type 1 diabetes, daily insulin therapy for
at least one year and an insulin infusion pump for at least 6 months; 15.0 to <46.0 years of
age; HbA1c < 10.0%; no DKA in last 6 months; no hypoglycemic seizure or loss of
consciousness in last 6 months; Living with a significant other or family member
("companion") committed to participating in all study activities, and being present and
available to provide assistance when the system is being used at night.
Sample Size: 30 subjects.
Study Duration and Visit Schedule: duration approximately 3 months, with preliminary run-in
activities followed by up to 90 days spent in clinical trial phase of study; clinic visits
at enrollment, following CGM and system assessment run-in phases, at start of clinical trial
phase, at 21-day point of clinical trial phase, and after 42 nights of successful system
use.
Major Efficacy Outcomes:
- Primary: time in range (70-180 mg/dl, 3.9-10.0 mmol/L) overnight.
- Secondary: time spent in hypoglycemia (≤70 mg/dl, 3.9 mmol/L) and time spent in
hyperglycemia (>180 mg/dl, 10.0 mmol/L) overnight.
Major Safety Outcomes: CGM measures of hypo- and hyperglycemia, including morning blood
glucose and mean overnight sensor glucose; adverse events including severe hypoglycemia and
diabetic ketoacidosis.
insulin to minimize projected hyperglycemia overnight in addition to suspending the pump if
hypoglycemia is projected overnight and to obtain feasibility, safety, and initial efficacy
data.
Study Design: randomized controlled trial, with randomization on a night level within
subject.
Major Eligibility Criteria: clinical diagnosis of type 1 diabetes, daily insulin therapy for
at least one year and an insulin infusion pump for at least 6 months; 15.0 to <46.0 years of
age; HbA1c < 10.0%; no DKA in last 6 months; no hypoglycemic seizure or loss of
consciousness in last 6 months; Living with a significant other or family member
("companion") committed to participating in all study activities, and being present and
available to provide assistance when the system is being used at night.
Sample Size: 30 subjects.
Study Duration and Visit Schedule: duration approximately 3 months, with preliminary run-in
activities followed by up to 90 days spent in clinical trial phase of study; clinic visits
at enrollment, following CGM and system assessment run-in phases, at start of clinical trial
phase, at 21-day point of clinical trial phase, and after 42 nights of successful system
use.
Major Efficacy Outcomes:
- Primary: time in range (70-180 mg/dl, 3.9-10.0 mmol/L) overnight.
- Secondary: time spent in hypoglycemia (≤70 mg/dl, 3.9 mmol/L) and time spent in
hyperglycemia (>180 mg/dl, 10.0 mmol/L) overnight.
Major Safety Outcomes: CGM measures of hypo- and hyperglycemia, including morning blood
glucose and mean overnight sensor glucose; adverse events including severe hypoglycemia and
diabetic ketoacidosis.
Subjects who are eligible for the clinical trial initially will use a Veo insulin pump and
Enlite 2 CGM sensor at home for a minimum of 6 days/week over a 2-week period to verify that
the subject is able to use the CGM and insert sensors.
The first 10 subjects enrolled will participate in a 2-day overnight hotel-based pilot,
collecting a total of 20 nights of data and experience with the system in a transitional
hotel setting. The DSMB will review safety data from the 20 night hotel-based pilot study
and make recommendations regarding proceeding to the at-home portion of the study.
Following DSMB review and approval of the safety data from the hotel study, the first 10
subjects will participate in an Algorithm Assessment Phase of approximately 10 nights of
Predictive Low Glucose Suspend (PLGS) + Hyper Minimization system use each (for a nominal
total of 100 nights of use at home) to determine if any adjustments to the algorithm
parameters are needed and if it is safe to advance to the randomized clinical trial phase.
If adjustments are needed, the Algorithm Assessment Phase will be repeated, using the same
10 subjects if possible. Once the randomized clinical trial phase begins, approximately 200
nights of randomized system use will be collected and assessed for safety by the DSMB before
proceeding.
New subjects who enroll in the study after the completion of the Algorithm Assessment Phase
will use the PLGS+Hyper Minimization closed-loop system at home for at least 5 days to
demonstrate their ability to use the system and submit study data to the Coordinating
Center.
Subjects who successfully demonstrate their ability to use the system at home as described
above will be eligible for the randomized trial phase. This phase consists of use of the
full system in the home for approximately 42 nights:
- Each night the blood glucose level will be checked with the BG meter and used to
perform a calibration of the CGM. This calibration must occur no more than 90 minutes
prior to activation of the system. NOTE: Subjects will be instructed to calibrate the
CGM per manufacturer guidelines.
- Then the system will be activated, linking the CGM and insulin pump to the computer at
the bedside.
- A randomization schedule on the laptop will be used to determine whether the system
will run in PLGS+Hyper Minimization mode or PLGS-only.
- Subjects will be blinded as to whether the system is running in PLGS+Hyper Minimization
mode or PLGS-only.
- There will not be an alarm if the pump shuts off or if automated insulin dosing occurs.
The CGM alarm will be set to 60 mg/dL (3.3 mmol/L). When a CGM alarm occurs, the
subject will be asked to measure the blood glucose with a BG meter, if he/she is aware
of the alarm.
- The time period for outcome assessment each night will be from the time the system is
activated until it is turned off in the morning.
- Pump shut off, when it occurs, will be for up to 120 minutes in a 150-minute period,
and no more than 180 minutes for the entire night. Multiple instances of pump
suspension can occur if there are recurrent predictions of hypoglycemia during the
night.
- Small correction boluses of insulin will be delivered when the system predicts that
hyperglycemia above a pre-set threshold will occur, with insulin-on-board constraints
and cumulative delivery limits to minimize the likelihood of excessive insulin
delivery.
- Subjects will be asked to check blood glucose with the study BG meter each morning
prior to breakfast and enter the results using the controller software interface. The
subject will be instructed to contact the study physician if the morning blood glucose
value is <60 mg/dl (3.3 mmol/L) or >300 mg/dl (16.7 mmol/L). Monitoring processes
detailed in section 3.11 will ensure that the subject can be contacted if these values
are not reported as required or are out of range.
- Subjects will be asked to record all overnight carbohydrate intake using the controller
software interface.
- Subjects will be asked to perform periodic CGM data uploads using the controller
software interface. Monitoring processes will ensure that the subject can be contacted
if these uploads do not occur as required, or if review of an upload reveals any
extreme, prolonged episodes of hypoglycemia or hyperglycemia, or elevated morning blood
glucose values.
Upon completion of the study, subjects as well as study clinicians will be asked to complete
a human factors usability questionnaire regarding use of the study system.
Enlite 2 CGM sensor at home for a minimum of 6 days/week over a 2-week period to verify that
the subject is able to use the CGM and insert sensors.
The first 10 subjects enrolled will participate in a 2-day overnight hotel-based pilot,
collecting a total of 20 nights of data and experience with the system in a transitional
hotel setting. The DSMB will review safety data from the 20 night hotel-based pilot study
and make recommendations regarding proceeding to the at-home portion of the study.
Following DSMB review and approval of the safety data from the hotel study, the first 10
subjects will participate in an Algorithm Assessment Phase of approximately 10 nights of
Predictive Low Glucose Suspend (PLGS) + Hyper Minimization system use each (for a nominal
total of 100 nights of use at home) to determine if any adjustments to the algorithm
parameters are needed and if it is safe to advance to the randomized clinical trial phase.
If adjustments are needed, the Algorithm Assessment Phase will be repeated, using the same
10 subjects if possible. Once the randomized clinical trial phase begins, approximately 200
nights of randomized system use will be collected and assessed for safety by the DSMB before
proceeding.
New subjects who enroll in the study after the completion of the Algorithm Assessment Phase
will use the PLGS+Hyper Minimization closed-loop system at home for at least 5 days to
demonstrate their ability to use the system and submit study data to the Coordinating
Center.
Subjects who successfully demonstrate their ability to use the system at home as described
above will be eligible for the randomized trial phase. This phase consists of use of the
full system in the home for approximately 42 nights:
- Each night the blood glucose level will be checked with the BG meter and used to
perform a calibration of the CGM. This calibration must occur no more than 90 minutes
prior to activation of the system. NOTE: Subjects will be instructed to calibrate the
CGM per manufacturer guidelines.
- Then the system will be activated, linking the CGM and insulin pump to the computer at
the bedside.
- A randomization schedule on the laptop will be used to determine whether the system
will run in PLGS+Hyper Minimization mode or PLGS-only.
- Subjects will be blinded as to whether the system is running in PLGS+Hyper Minimization
mode or PLGS-only.
- There will not be an alarm if the pump shuts off or if automated insulin dosing occurs.
The CGM alarm will be set to 60 mg/dL (3.3 mmol/L). When a CGM alarm occurs, the
subject will be asked to measure the blood glucose with a BG meter, if he/she is aware
of the alarm.
- The time period for outcome assessment each night will be from the time the system is
activated until it is turned off in the morning.
- Pump shut off, when it occurs, will be for up to 120 minutes in a 150-minute period,
and no more than 180 minutes for the entire night. Multiple instances of pump
suspension can occur if there are recurrent predictions of hypoglycemia during the
night.
- Small correction boluses of insulin will be delivered when the system predicts that
hyperglycemia above a pre-set threshold will occur, with insulin-on-board constraints
and cumulative delivery limits to minimize the likelihood of excessive insulin
delivery.
- Subjects will be asked to check blood glucose with the study BG meter each morning
prior to breakfast and enter the results using the controller software interface. The
subject will be instructed to contact the study physician if the morning blood glucose
value is <60 mg/dl (3.3 mmol/L) or >300 mg/dl (16.7 mmol/L). Monitoring processes
detailed in section 3.11 will ensure that the subject can be contacted if these values
are not reported as required or are out of range.
- Subjects will be asked to record all overnight carbohydrate intake using the controller
software interface.
- Subjects will be asked to perform periodic CGM data uploads using the controller
software interface. Monitoring processes will ensure that the subject can be contacted
if these uploads do not occur as required, or if review of an upload reveals any
extreme, prolonged episodes of hypoglycemia or hyperglycemia, or elevated morning blood
glucose values.
Upon completion of the study, subjects as well as study clinicians will be asked to complete
a human factors usability questionnaire regarding use of the study system.
Inclusion Criteria:
- Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least
one year and an insulin infusion pump for at least 6 months The diagnosis of type 1
diabetes is based on the investigator's judgment; C peptide level and antibody
determinations are not required.
- Age 15.0 to <46.0 years
- HbA1c <10.0%
- Measured with DCA2000 or equivalent device for assessing eligibility
- HbA1c measurements performed as part of usual clinical care within 2 weeks prior
to obtaining informed consent for participation in the trial may be used.
- Uninterrupted internet access while study system is being used overnight and for
upload of study data in the morning
- Living with a significant other or family member ("companion") committed to
participating in all study activities, and being present and available to provide
assistance when the system is being used at night
- An understanding of and willingness to follow the protocol and sign the informed
consent
Exclusion Criteria:
- Diabetic ketoacidosis in the past 3 months
- Hypoglycemic seizure or loss of consciousness in the past 6 months
- History of seizure disorder (except for hypoglycemic seizure)
- History of any heart disease including coronary artery disease, heart failure, or
arrhythmias
- Cystic fibrosis
- Current use of oral/inhaled glucocorticoids, beta-blockers or other medications,
which in the judgment of the investigator would be a contraindication to
participation in the study.
- History of ongoing renal disease (other than microalbuminuria). Creatinine level must
have been obtained within the last year if subject has diabetes of >10 years
duration. If creatinine is >1.5 mg/dL (132 µmol/L), the subject is excluded.
- Medical or psychiatric condition that in the judgment of the investigator might
interfere with the completion of the protocol such as:
- Inpatient psychiatric treatment in the past 6 months
- Uncontrolled adrenal disorder
- Abuse of alcohol
- Pregnancy Negative urine pregnancy test required for females who have experienced
menarche as well as agreement from subject and parent/guardian to use a form of
contraception to prevent pregnancy while participant is in the study. Subjects who
become pregnant will be discontinued from the study.
- Liver disease as defined by an ALT greater than 3 times the upper limit of normal
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Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
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