Glucose Control for Glucocorticoid Induced Hyperglycemia During Chemotherapy

Study Overview
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Brief Summary
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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.

Official Title
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Glucose Control for Glucocorticoid Induced Hyperglycemia During Chemotherapy

Conditions
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Hyperglycemia Steroid-induced

Intervention / Treatment
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* Drug: Sliding scale insulin
* Drug: Intermediate acting insulin
* Behavioral: Dietary advice
* Drug: Glucose lowering medication
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sliding scale insulin<br>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<br> <br> * Other names: Short acting insulin on a sliding scale base;Behavioral: Dietary advice<br>* Dietary advice to avoid food products with high glycemic index / high glucose load<br>Drug: Glucose lowering medication<br>* Regular glucose lowering medication as prescribed by the patient's own physician before study entry<br>Drug: Chemotherapy<br>* Chemotherapy (containing glucocorticoids) as prescribed by the patient's own physician<br>* Other names: Antineoplastic therapy;|
| Experimental: Intermediate acting insulin<br>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) | Drug: Intermediate acting insulin<br> <br> * Other names: NPH insulin, insulatard;Behavioral: Dietary advice<br>* Dietary advice to avoid food products with high glycemic index / high glucose load<br>Drug: Glucose lowering medication<br>* Regular glucose lowering medication as prescribed by the patient's own physician before study entry<br>Drug: Chemotherapy<br>* Chemotherapy (containing glucocorticoids) as prescribed by the patient's own physician<br>* Other names: Antineoplastic therapy;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoid induced hyperglycemia, insulin, chemotherapy