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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sliding scale insulin | Active Comparator | 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 | Experimental | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sliding scale insulin | Drug |
|
| |
| 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) |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Slotervaart Hospital | Amsterdam | 1066 EC | Netherlands | |||
| Antoni van Leeuwenhoek hospital |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D007336 | Insulin, Isophane |
| D000068880 | Isophane Insulin, Human |
| D015596 | Nutrition Assessment |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| Intermediate acting insulin |
| Drug |
|
|
| Dietary advice | Behavioral | Dietary advice to avoid food products with high glycemic index / high glucose load |
|
| Glucose lowering medication | Drug | Regular glucose lowering medication as prescribed by the patient's own physician before study entry |
|
| Chemotherapy | Drug | Chemotherapy (containing glucocorticoids) as prescribed by the patient's own physician |
|
|
| 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) |
| Amsterdam |
| 1066EC |
| Netherlands |
| Isala Clinics | Zwolle | 8025 AB | Netherlands |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061386 | Insulin, Regular, Human |
| D007328 | Insulin |
| D011384 | Proinsulin |
| D003625 | Data Collection |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
| D015991 | Epidemiologic Measurements |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D013812 | Therapeutics |