Reduction of Nocturnal Hypoglycemia and Hyperglycemia in the Home Using Predictive Algorithms, Pump Suspension, and Insulin Dosing in Children and Young Adolescents (PHM3)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 4
- 主要终点
- Comparison of percent time in range overnight between the two treatment arms
研究概览
简要总结
Objective: to gain experience in children and younger adolescents with in-home use of an 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 Patient Population: Youth 6.0 - <15 years old with type 1 diabetes treated with daily insulin therapy for at least one year and an insulin infusion pump for at least 6 months who have HbA1c < 10.0%.
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
详细描述
Subjects who are eligible for the clinical trial initially will use a Veo insulin pump and Enlite 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 be 11 to <15 years of age and will participate in an Algorithm Assessment Phase of approximately 10 nights of system use each with PLGS and Hyper Minimization active. Results of the approximate 100 nights will be reviewed with the study DSMB to assess safety and determine whether any adjustments to the algorithm parameters are needed. If adjustments are needed, the Algorithm Assessment Phase will be repeated with the same age restriction, using the same 10 subjects if possible. If no adjustments are needed and the DSMB judges it safe to continue the study, enrollment will continue across the full 6 to <15 age range.
Subjects who enroll in the study after the completion of the Algorithm Assessment Phase will use the closed-loop system at home for 5 nights of system use each with PLGS and Hyper Minimization active 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Subjects are randomized on a per-night level for when the PHHM will be active or not.
入排标准
- 年龄范围
- 6 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 6.0 to <15.0 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 family member/guardian ("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
排除标准
- •Diabetic ketoacidosis in the past 6 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
结局指标
主要结局
Comparison of percent time in range overnight between the two treatment arms
时间窗: Up to 42 nights
A single percentage calculated for each subject by pooling all CGM readings from the PLSG+HM nights will be compared with the corresponding percentage obtained by pooling all of the data from PLGS-only nights for the same subject. All CGM readings regardless of the amount of data will be weighted equally in the pooled percentage regardless of how they distribute across nights.
次要结局
- Glucose standard deviation and coefficient of variation(Up to 42 nights)
- Mean overnight sensor glucose(Up to 42 nights)
- Percent of sensor measurements below 50 mg/dl (2.8 mmol/L)(Up to 42 nights)
- Percent of sensor measurements below 60 mg/dl (3.3 mmol/L)(Up to 42 nights)
- Percent of sensor measurements below 70 mg/dl (3.9 mmol/L)(Up to 42 nights)
- Area under the curve 70 mg/dl (3.9 mmol/L)(Up to 42 nights)
- Low blood glucose index(Up to 42 nights)
- Percent of sensor measurements above 180 mg/dl (10.0 mmol/L)(Up to 42 nights)
- Percent of sensor measurements above 250 mg/dl (13.9 mmol/L)(Up to 42 nights)
- Percentage of nights with events of sensor glucose below 50 mg/dl (2.8 mmol/L), 60 mg/dl (3.3 mmol/L), and 70 mg/dl (3.9 mmol/L) cumulatively for more than 30, 60, 120, and 180 minutes(Up to 42 nights)
- Percentage of nights with events of sensor glucose above 180 mg/dl (10.0 mmol/L), 250 mg/dl (13.9 mmol/L), and 300 mg/dl (16.7 mmol/L) continuously for more than 0, 30, 60, and 120 minutes(Up to 42 nights)
- Percentage of nights with events of sensor glucose above 180 mg/dl (10.0 mmol/L), 250 mg/dl (13.9 mmol/L), and 300 mg/dl (16.7 mmol/L) cumulatively for more than 60, 120, and 180 minutes(Up to 42 nights)
- Mean morning blood glucose (subject-level data) and percent of morning with blood glucose below 50 mg/dl (2.8 mmol/L), 60 mg/dl (3.3 mmol/L), 70 mg/dl (3.9 mmol/L) (night-level data)(Up to 42 nights)
- Mean morning blood glucose (subject-level data) and percent of morning with blood glucose between 70 mg/dl (3.9 mmol/L) and 180 mg/dl (10.0 mmol/L) (night-level data)(Up to 42 nights)
- Mean morning blood glucose (subject-level data) and percent of morning with blood glucose above 180 mg/dl (10.0 mmol/L), 250 mg/dl (13.9 mmol/L), and 300 mg/dl (16.7 mmol/L) (night-level data)(Up to 42 nights)
- Amount of total (manual, automatic, combined) and insulin boluses(Up to 42 nights)
- Percent of sensor measurements above 300 mg/dl (16.7 mmol/L)(Up to 42 nights)
- Area under the curve 180 mg/dl (10.0 mmol/L)(Up to 42 nights)
- High blood glucose index(Up to 42 nights)
- Percent of sensor measurements between 70 mg/dl (3.9 mmol/L)(Up to 42 nights)
- Percent of sensor measurements between 140 mg/dl (7.8 mmol/L)(Up to 42 nights)
- Percentage of nights with events of sensor glucose below 50 mg/dl (2.8 mmol/L), 60 mg/dl (3.3 mmol/L), and 70 mg/dl (3.9 mmol/L) continuously for more than 0, 10, 25, 30, 60, and 120 minutes(Up to 42 nights)