Glucose Control for Glucocorticoid Induced Hyperglycemia During Chemotherapy (GluCon-Chemo)

Objective: to determine which regimen results in best glycemic control and safety profile, expressed as glucose values within target range and occurrence of hypoglycemia. Secondary objective is to compare patient satisfaction, clinical outcomes and toxicity.

Study design: Randomized open label cross-over study Study population: Patients ≥ 18 years, who developed glucocorticoid induced hyperglycemia requiring initiation or adjustment of antihyperglycemic agents in a previous chemotherapy cycle. Patient should have ≥2 cycles of chemotherapy scheduled, with 3-10 consecutive days of ≥12,5mg prednisone-equivalent glucocorticoid and a wash-out period of 4-38 days between each cycle.

Intervention: subjects will be treated by insulin regimen A and B in random order during two consecutive cycles of chemotherapy. A) intermediate acting insulin 0.01 IU / mg prednisone-equivalent / kg body weight once daily subcutaneous B) Short-acting insulin according to sliding scale regimen, dose adjusted to current grade of hyperglycemia.

Main study parameters: Difference in fraction of blood glucose measurements (BGM) within target range and occurrence of hypoglycemia.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Both study treatments are just a slight variation in regular care for glucocorticoid induced hyperglycemia. Glycemic control is likely to improve due to treatments and increased counselling. All subjects will receive both treatment regimens.

The burden consists of 16-32 extra BGMs over 2 x 4-10 days, wearing the glucose sensor, 1 venipuncture (if HbA1c and creatinin are not determined in routine laboratory within 3 months before start), and 1 randomization visit to the outpatient clinic. Potential risk is the occurrence of hypoglycemia, as is present in any insulin therapy. The investigators account for this risk by giving subjects dietary advice and education how to prevent, recognize and treat hypoglycemia.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia Steroid-induced
• Intervention / Treatment: Drug: Sliding scale insulin; Behavioral: Dietary advice; Drug: Glucose lowering medication; Drug: Chemotherapy; Drug: Intermediate acting insulin

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 EC
    • Slotervaart Hospital
  • Amsterdam, Netherlands, 1066EC
    • Antoni van Leeuwenhoek Hospital
  • Zwolle, Netherlands, 8025 AB
    • Isala Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Written informed consent
• Glucocorticoid induced hyperglycemia in previous cycle of chemotherapy that required therapy initiation or adjustment
• Duration of glucocorticoid cycles 3-10 consecutive days and 4-38 glucocorticoid-free days between 2 cycles
• Prednisone-equivalent dose of ≥ 12,5mg
• At least 2 more cycles of chemotherapy to receive

Exclusion Criteria:

• History of hypo-unawareness
• Continuous tube or parental feeding
• Continuous (maintenance) systemic glucocorticoid therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sliding scale insulin; Sliding scale insulin Glucose 7.8-12 mmol/l --> 2 IU insulin, glucose 12.1-17 mmol/l --> 4 IU insulin, glucose ≥17.1 mmol/l --> 6 IU insulin. In case of insufficient control, insulin doses will be increased	Drug: Sliding scale insulin; Other Names: Short acting insulin on a sliding scale base; Behavioral: Dietary advice; Dietary advice to avoid food products with high glycemic index / high glucose load; Drug: Glucose lowering medication; Regular glucose lowering medication as prescribed by the patient's own physician before study entry; Drug: Chemotherapy; Chemotherapy (containing glucocorticoids) as prescribed by the patient's own physician; Other Names: Antineoplastic therapy
Experimental: Intermediate acting insulin; Intermediate acting insulin, 0.01 IU / mg prednison / kg body weight with a maximum of 0.5 unit insulin per kg body weight. In case of age > 70 years or diminished renal function (GFR <30ml/min)	Behavioral: Dietary advice; Dietary advice to avoid food products with high glycemic index / high glucose load; Drug: Glucose lowering medication; Regular glucose lowering medication as prescribed by the patient's own physician before study entry; Drug: Chemotherapy; Chemotherapy (containing glucocorticoids) as prescribed by the patient's own physician; Other Names: Antineoplastic therapy; Drug: Intermediate acting insulin; Other Names: NPH insulin, insulatard

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control	Compare achievement of glycemic control in SSI therapy and intermediate acting insulin. Glycemic control is measured as the proportion of blood glucose measurements (BGM) within target range in each subject after 24h of treatment	24h till end of treatment (expected duration 4-8 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction	Compare patient satisfaction in each treatment regimen at a 6-point Likert scale, in the last cycle we evaluate patient's preference for glucose lowering treatment in next chemotherapy cycle (SSI or intermediate acting insulin)	At the end of each treatment cycle (expected duration 4-8 days)
Clinical outcomes	Difference in clinical outcomes: incidence of oral candidiasis, pooled incidence of grade 3-4 chemotoxicity. Data on clinical outcomes will be collected by taking the patient history at the end of each treatment cycle.	During each treatment (expected duration 4-8 days)
Hypoglycemia	Incidence of hypoglycemia in each treatment cycle defined as an interstitial glucose ≤ 3.9 mmol/l continuing until the interstitial glucose is >3.9 mmol/l	During each treatment (expected duration 4-8 days)

Collaborators and Investigators

• Sponsor: Slotervaart Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 4, 2014

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Glucocorticoid induced hyperglycemia, insulin, chemotherapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Antineoplastic Agents; Insulin, Short-Acting
• Other Study ID Numbers: NL47135.048.13