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Outpatient Reduction of Nocturnal Hypoglycemia by Using Predictive Algorithms and Pump Suspension in Children (PSO4)

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ClinicalTrials.gov Identifier: NCT01823341
Recruitment Status : Completed
First Posted : April 4, 2013
Results First Posted : August 24, 2015
Last Update Posted : August 30, 2016
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Jaeb Center for Health Research

Tracking Information
First Submitted Date  ICMJE March 29, 2013
First Posted Date  ICMJE April 4, 2013
Results First Submitted Date  ICMJE June 25, 2015
Results First Posted Date  ICMJE August 24, 2015
Last Update Posted Date August 30, 2016
Study Start Date  ICMJE May 2013
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2015)
Comparison of the Time Spent in Hypoglycemia (<70 mg/dl, 3.9 mmol/L) Overnight on Intervention Nights Versus Control Nights, Normalized to an 8-hour Period. [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use. ]
Each night is categorized as to whether hypoglycemia occurred. Hypoglycemia is defined as the occurrence of one or more CGM glucose values ≤70 mg/dL (3.9 mmol/L). The time period for outcome assessment each night will be from the time the system is activated in the evening until the time it is deactivated in the morning. The percentage of hypoglycemic nights (CGM glucose value ≤70 mg/dL (3.9 mmol/L)) will be tabulated separately with versus without the closed-loop control system in use. We considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2013)
Comparison of intervention nights and control nights in which hypoglycemia occurred [ Time Frame: 42 nights ]
Each night is categorized as to whether hypoglycemia occurred. Hypoglycemia is defined as the occurrence of one or more CGM glucose values ≤60 mg/dL (3.3 mmol/L). The time period for outcome assessment each night will be from the time the system is activated in the evening until the time it is deactivated in the morning. The percentage of hypoglycemic nights (CGM glucose value ≤60 mg/dL (3.3 mmol/L)) will be tabulated separately with versus without the closed-loop control system in use.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2015)
  • Percentage of Nights With 1 or More Sensor Glucose Values <70 mg/dL (<3.9 mmol/L) [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use. ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Percentage of Nights With 1 or More Sensor Glucose Values <50 mg/dL (<2.8 mmol/L) [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Mean Sensor Glucose Overnight [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Percentage of Time Overnight Sensor Glucose Values 71 to 180 mg/dL (3.9 to 10.0 mmol/L), Normalized to an 8-hour Period. [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Percentage of Overnight Time Spent With CGM Value >250 mg/dL (13.9 mmol/L), Normalized to an 8-hour Period. [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Mean Morning Blood Glucose [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Percentage of Mornings With Blood Glucose >250 mg/dL (>13.9 mmol/L) [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Morning Blood Ketones >=1.0 mmol/L [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Please note we considered nights with at least 4 hours of sensor glucose data as a "valid" night toward the 42 night overall goal and thus our final analyses had a slightly higher number of nights than expected.
  • Percent of Mornings With Urine Ketones >/= 15 mg/dl [ Time Frame: Overnight from system activation to deactivation in the morning upon awakening for 42 nights of system use ]
    Urine ketones measured each morning with Ketostix.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2013)
  • Percentage of sensor glucose values 71 to 180 mg/dL (3.9 to 10.0 mmol/L) [ Time Frame: 42 nights ]
  • Proportion of nights with a sensor glucose value <=70 mg/dL (<=3.9 mmol/L) [ Time Frame: 42 nights ]
  • Proportion of nights with sensor glucose value <=50 mg/dL (<=2.8 mmol/L) [ Time Frame: 42 nights ]
  • For the nights when sensor glucose is <=60 mg/dL (<= 3.3 mmol/L), tabulation will be made as to whether blood glucose measured with study blood glucose meter [ Time Frame: 42 nights ]
    For instances where blood glucose was measured using a study blood glucose meter, a comparison will be made between the sensor glucose values and meter blood glucose values.
  • Mean home glucose meter morning glucose [ Time Frame: 42 nights ]
  • Morning glucose measured with home glucose meter >=250 mg/dL (>=13.9 mmol/L) [ Time Frame: 42 nights ]
  • Morning blood ketones >1.0 mmol/L [ Time Frame: 42 nights ]
  • Morning urine ketones >=small amount [ Time Frame: 42 nights ]
  • Mean Sensor Glucose Overnight [ Time Frame: 42 nights ]
    Mean sensor glucose will be assessed over 24 hours and for 4 hours post system deactivation.
  • Percentage of sensor glucose values 71 to 180 mg/dL (3.9 to 10.0 mmol/L) overnight [ Time Frame: 42 nights ]
    Percentage of sensor glucose values 71 to 180 mg/dL (3.9 to 10.0 mmol/L) overnight assessed over 24 hours and over the first 4 hours following system deactivation.
  • Area under the curve for sensor glucose <70 mg/dL (3.9 mmol/L), 60 mg/dL (3.3 mmol/L), and 50 mg/dL (2.8 mmol/L) [ Time Frame: 42 nights ]
    Area under the curve will be assessed over 24 hours and over the first 4 hours following system deactivation.
  • Area under the curve sensor glucose >180 mg/dL (10.0 mmol/L) and 240 mg/dl (13.3 mmol/L) overnight [ Time Frame: 42 nights ]
    Area under the curve will be assessed over 24 hours and over the first 4 hours following system deactivation.
  • Percent of nights with a CGM value > 250 mg/dL (13.9 mmol/L) [ Time Frame: 42 nights ]
  • Morning glucose measured with home glucose meter >250 mg/dL (13.9 mmol/L) [ Time Frame: 42 nights ]
  • Morning ketones >0.6 mmol/L [ Time Frame: 42 nights ]
  • Episodes of Diabetic Ketoacidosis (DKA) [ Time Frame: 42 nights ]
  • Episodes of severe hypoglycemia [ Time Frame: 42 nights ]
  • Change in Hemoglobin A1c [ Time Frame: 42 nights ]
  • All reported adverse events [ Time Frame: 42 nights ]
  • The pump settings will be analyzed for any changes from the baseline visit [ Time Frame: 21 and 42 nights ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Outpatient Reduction of Nocturnal Hypoglycemia by Using Predictive Algorithms and Pump Suspension in Children
Official Title  ICMJE Outpatient Reduction of Nocturnal Hypoglycemia by Using Predictive Algorithms and Pump Suspension in Children
Brief Summary

The purpose of this study is to see whether low blood sugar at night can be reduced by using a system that turns off the insulin pump automatically. The study system includes a continuous glucose monitor (CGM) and an insulin pump. The CGM and pump work with a regular laptop computer. A The system works by (1) measuring the glucose levels under the skin with the CGM, (2) using a computer program on the laptop to predict whether a low blood sugar is likely to occur, and (3) turning off the insulin pump when the computer program predicts that a low blood sugar will occur.

We have tested the system in the home environment in individuals with type 1 diabetes age 15 years and older. We have found an indication that the system can decrease the frequency of hypoglycemia. We have not had any serious cases of high blood sugars or other problems. We are now ready to further test the system in the home environment in a younger age group to learn more about its ability to reduce overnight low blood sugar risk.

This study has several phases and will take about 3 months for a patient to complete.

  • First, the patient will use the CGM and pump at home for up to 15 days with the help of a parent/guardian. This is done to determine if the patient meets our study criteria to proceed with the next phase of the study.
  • If the patient is eligible to continue in the study, the patient will need to use the full study system for at least 5 nights at home with the help of a parent/guardian. This is done to make sure the patient and parent/guardian are able to use the system correctly. The patient may participate in starting and stopping the system at home, but the parent/guardian is responsible for making sure it is used as instructed.
  • After that, the patient will be asked to use the study system each night for an additional 6 to 8 weeks. The parent/guardian will remain responsible for making sure the system is used as instructed.

The study will include about 90 individuals with type 1 diabetes at 3 clinical centers in the United States and Canada. First a study of children 8 to less than 15 years old will be done. Then, a study of children 3 to less than 8 years old will be conducted.

Detailed Description

Patients who are eligible for the clinical trial initially will use a Veo insulin pump and Enlite sensor at home to verify that the patient is able to use the continuous glucose monitor (CGM) and insert sensors and is eligible to continue in the study. A parent or guardian of the child subject will oversee the actions of the subject and be responsible for the patient's overall participation during the proposed study, including operation of the investigational device system.

The first 10 patients 8 to <15 years of age will participate in an Algorithm Assessment Phase of approximately 10 nights of active system use each (for a nominal total of 100 nights of use) to determine if any adjustments to the algorithm parameters are needed and if it is safe to advance to a randomized clinical trial phase with these subjects. If adjustments are needed, the Algorithm Assessment Phase will be repeated, using the same 10 patients if possible. Once the randomized clinical trial phase begins for patients 8 to <15 years of age, approximately 200 nights of randomized system use will be collected and assessed for safety before any patients 3 to <8 years of age may be enrolled in the study. When enrollment does begin for patients 3 to <8 years of age, a second Algorithm Assessment Phase will be conducted with the first 10 patients in that younger age group using the same approach described above for the older subjects. Once the randomized clinical trial phase begins for patients 3 to <8 years of age, a final Data Safety Monitoring Board safety assessment will be performed after approximately the first 200 nights of randomized system use.

Patients who enroll in the study after the completion of the Algorithm Assessment Phase for their age group will use the 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.

Patients 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 as an outpatient for approximately 42 nights:

  • Each night the blood glucose (BG) 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 'pump shut off' application will be active that night or not.
  • Patients will be blinded as to whether the pump shut off is active when a session is initiated each night.
  • There will not be an alarm if the pump shuts off. 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.
  • Patients will be asked to check blood ketones with the study ketone meter if the subject has a fingerstick BG ≥250 mg/dL (13.9 mmol/L).
  • Patients will be asked to check blood glucose with the study BG meter, blood ketones with the study ketone meter, and urine ketones with a ketone strip each morning prior to breakfast and enter the results using the controller software interface. The patient will be instructed to contact the study physician if the blood glucose or ketone readings are out of an expected range.
  • Patients will be asked to record all overnight carbohydrate intake using the controller software interface.
  • Patients will be asked to perform periodic CGM data uploads using the controller software interface.

Upon completion of the study, patients as well as study clinicians will be asked to complete a human factors usability questionnaire regarding use of the study system.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE Device: Pump suspension algorithm
The study laptop will communicate to the pump causing a suspension based on output from the algorithm which predicts hypoglycemia.
Study Arms  ICMJE
  • Active Comparator: Pump suspension algorithm
    The pump suspension algorithm will be running actively on the study laptop during the night and suspend the pump if the algorithm predicts hypoglycemia.
    Intervention: Device: Pump suspension algorithm
  • No Intervention: Standard of Care
    The control algorithm will run passively and not suspend the patient's pump.
Publications * Buckingham BA, Raghinaru D, Cameron F, Bequette BW, Chase HP, Maahs DM, Slover R, Wadwa RP, Wilson DM, Ly T, Aye T, Hramiak I, Clarson C, Stein R, Gallego PH, Lum J, Sibayan J, Kollman C, Beck RW; In Home Closed Loop Study Group. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis. Diabetes Care. 2015 Jul;38(7):1197-204. doi: 10.2337/dc14-3053. Epub 2015 Jun 6. Erratum in: Diabetes Care. 2015 Sep;38(9):1813.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 27, 2015)
97
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2013)
120
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Age 3 to <15 years
  • HbA1c <=8.5%
  • Availability of internet access for periodic upload of study data

Exclusion Criteria:

  • Diabetic ketoacidosis in the past 3 months
  • Hypoglycemic seizure or loss of consciousness in past 6 months
  • History of seizure disorder (except for hypoglycemic seizures)
  • 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), or liver disease (Creatinine is > 1.5 mg/dL (132 µmol/L))
  • 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
  • Liver disease as defined by an Alanine Aminotransferase Test (ALT) greater than 3 times the upper limit of normal
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 14 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01823341
Other Study ID Numbers  ICMJE PSO4
5R01DK085591 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jaeb Center for Health Research
Study Sponsor  ICMJE Jaeb Center for Health Research
Collaborators  ICMJE
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Juvenile Diabetes Research Foundation
Investigators  ICMJE
Principal Investigator: Roy W Beck, MD, PhD Jaeb Center for Health Research
Study Chair: Bruce A Buckingham, MD Stanford University
Study Director: John Lum, MS Jaeb Center for Health Research
PRS Account Jaeb Center for Health Research
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP