Glucose Control for Glucocorticoid Induced Hyperglycemia During Chemotherapy

Phase 4

Completed

• Conditions: Hyperglycemia Steroid-induced
• Interventions: Drug: Intermediate acting insulin; Drug: Sliding scale insulin; Behavioral: Dietary advice; Drug: Glucose lowering medication; Drug: Chemotherapy

• Registration Number: NCT02155374
• Lead Sponsor: Slotervaart Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-05-05
• Study First Submitted QC: 2014-06-02
• Study First Posted: 2014-06-04
• Primary Completion: 2015-12
• Status Verified: 2016-01
• Study Completion: 2016-01
• Last Update Submitted: 2016-01-06
• Last Update Posted: 2016-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sliding scale insulin	Glucose lowering medication	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
Intermediate acting insulin	Chemotherapy	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)
Sliding scale insulin	Dietary advice	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
Intermediate acting insulin	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)
Intermediate acting insulin	Dietary advice	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)
Sliding scale insulin	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
Sliding scale insulin	Chemotherapy	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
Intermediate acting insulin	Glucose lowering medication	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)

Primary Outcome Measures

Name	Time	Method
Glycemic control	24h till end of treatment (expected duration 4-8 days)	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

Secondary Outcome Measures

Name	Time	Method
Patient satisfaction	At the end of each treatment cycle (expected duration 4-8 days)	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)
Clinical outcomes	During each treatment (expected duration 4-8 days)	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.
Hypoglycemia	During each treatment (expected duration 4-8 days)	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

Trial Locations

Locations (3)

Antoni van Leeuwenhoek hospital; 🇳🇱 Amsterdam, Netherlands

Isala Clinics; 🇳🇱 Zwolle, Netherlands

Slotervaart Hospital; 🇳🇱 Amsterdam, Netherlands