HCL Single Arm Pilot Study in Treatment of Hyperglycemia of Pediatric ALL

Early Phase 1

Terminated

• Conditions: High Risk Acute Lymphoblastic Leukemia
• Interventions: Device: Hybrid Closed Loop System

• Registration Number: NCT05006040
• Lead Sponsor: University of Colorado, Denver

Brief Summary

The overall objective of this pilot study is to determine the safety and feasibility of a hybrid closed-loop insulin delivery system for children and young adults with high risk acute lymphoblastic leukemia, during the induction chemotherapy phase while they are exposed to steroids and asparaginase that cause hyperglycemia.

Detailed Description

The overall objective of this pilot study is to determine the safety and feasibility of a hybrid closed-loop insulin delivery system for children and young adults with high risk acute lymphoblastic leukemia, during the induction chemotherapy phase while they are exposed to steroids and asparaginase that cause hyperglycemia. Insulin therapy would be beneficial in reducing hyperglycemia-associated complications in this period and thereby could improve other outcomes. The primary objective of the current pilot proposal is to demonstrate that hybrid closed loop pump therapy is a safe to be used in children and young adults with high risk acute lymphoblastic leukemia. If successful, the results of this study will be used to plan and support a larger, multi-center clinical trial and a grant proposal.

Study Timeline

• Study First Submitted: 2021-07-07
• Study First Submitted QC: 2021-08-06
• Study First Posted: 2021-08-16
• Study Start: 2022-05-12
• Primary Completion: 2022-06-17
• Study Completion: 2023-08-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

1. Patients ages 10 years old and above
2. Patients who are newly diagnosed with high-risk acute lymphoblastic leukemia
3. Patients who have started or will start an induction chemotherapy regimen containing steroid and asparaginase
4. Patients (if over 18 years of age) or parent/guardian (if the patient is under 18 years of age) must be fluent in reading and speaking English
5. Parent or guardian living in the home with the participant who also receives training on diabetes, CGM, HCL therapy, and the safety protocols

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Exclusion Criteria

1. Preexisting diabetes

2. Severe psychiatric disease or developmental delays, that might interfere with ability to provide informed consent

3. Active skin condition that would affect sensor placement

4. Any other medical condition which in the opinion of the investigators impairs the person's ability to safely participate in the trial, including but limited to:

   1. Significant chronic kidney disease (eGFR <60) or requiring hemodialysis
   2. Significant liver disease
   3. History of adrenal insufficiency
   4. History of abnormal TSH consistent with hypothyroidism or hyperthyroidism that is not appropriately treated
   5. History of thyroid cancer

5. Use of intravenous or oral acetaminophen more than 60 mg/kg/day (maximum 4000 mg/day)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hybrid Closed-Loop Insulin System During Chemo with Steroid and Asparaginase	Hybrid Closed Loop System	Subjects will receive insulin via hybrid closed-loop insulin delivery system during the chemotherapy phases that contains steroid and asparaginase. This treatment will be initiated within 4 days of starting induction chemotherapy treatment.

Primary Outcome Measures

Name	Time	Method
Rate of infection at the CGM insertion site	35 days	Rate of infection at the CGM insertion site, measured in occurrences per patient-day.
Rate of bleeding at the CGM insertion site	35 days	Rate of bleeding at the CGM insertion site, measured in occurrence per patient-day.
CGM Time in hypoglycemia (blood glucose < 70 mg/dL)	35 days	The primary outcome measures for this study will be the safety of HCL insulin delivery by hypoglycemia exposure. One of the primary endpoints is CGM Time in hypoglycemia (defined as blood glucose \< 70 mg/dL).
Number of episodes of symptomatic hypoglycemia	35 days	The primary outcome measures for this study will be the safety of HCL insulin delivery by hypoglycemia exposure. One of the primary endpoints is the number of episodes of symptomatic hypoglycemia. At each study visit, subjects will be asked about symptoms, such as shakiness, dizziness, blurred/impaired vision, sweating, pallor, clumsiness, difficulty paying attention, tingling around the lips, tongue or cheeks, change in mental status, or seizure.
Rate of infection at the HCL insulin infusion site	35 days	Rate of infection at the HCL insulin infusion site, measured in occurrence per patient-day.
Rate of bleeding at the HCL insulin infusion site	35 days	Rate of bleeding at the HCL insulin infusion site, measured in occurrence per patient-day.

Secondary Outcome Measures

Name	Time	Method
Need for readmission during the induction phase in percent	35 days	Rate of infection, length of hospitalization, length of PICU admission, rate of remission at the end of induction, and need for re-admission will be obtained as a part of clinical outcomes. These outcomes will be compared to a historical control group to investigate the effect size of relationships between glycemic control and clinical outcome. This exploratory aim will investigate correlations between glycemic control and outcomes to determine effect sizes for future studies and grant proposals.
Length of PICU admission in days per patient	35 days	Rate of infection, length of hospitalization, length of PICU admission, rate of remission at the end of induction, and need for re-admission will be obtained as a part of clinical outcomes. These outcomes will be compared to a historical control group to investigate the effect size of relationships between glycemic control and clinical outcome. This exploratory aim will investigate correlations between glycemic control and outcomes to determine effect sizes for future studies and grant proposals.
Rate of remission at the end of induction in percent	35 days	Rate of infection, length of hospitalization, length of PICU admission, rate of remission at the end of induction, and need for re-admission will be obtained as a part of clinical outcomes. These outcomes will be compared to a historical control group to investigate the effect size of relationships between glycemic control and clinical outcome. This exploratory aim will investigate correlations between glycemic control and outcomes to determine effect sizes for future studies and grant proposals.
Efficacy of glycemic control with HCL insulin delivery assessed by mean sensor glucose level	35 days	Mean glucose level will be obtained from CGM data to evaluate for glycemic variability
Length of hospitalization in days per patient	35 days	Rate of infection, length of hospitalization, length of PICU admission, rate of remission at the end of induction, and need for re-admission will be obtained as a part of clinical outcomes. These outcomes will be compared to a historical control group to investigate the effect size of relationships between glycemic control and clinical outcome. This exploratory aim will investigate correlations between glycemic control and outcomes to determine effect sizes for future studies and grant proposals.
Efficacy of glycemic control with HCL insulin delivery assessed by Time in Ranges (TIR)	35 days	Time in Ranges (TIRs) refers to percent of the time spent in a specific range of blood glucose levels, adding valuable information to assess the level of glycemic control. Usually a range of 70-180 mg/dL is used, but occasionally a more stringent 70-140 mg/dL is used. In this study, we will obtain %CGM TIRs in both ranges.
Rate of infection in episodes per patient-days	35 days	Rate of infection, length of hospitalization, length of PICU admission, rate of remission at the end of induction, and need for re-admission will be obtained as a part of clinical outcomes. These outcomes will be compared to a historical control group to investigate the effect size of relationships between glycemic control and clinical outcome. This exploratory aim will investigate correlations between glycemic control and outcomes to determine effect sizes for future studies and grant proposals.

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States