Intraperitoneal vs Subcutaneous Insulin Administration in Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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Almost all patients with type 1 diabetes mellitus (T1DM) need insulin treatment permanently. For selected patients who are unable to achieve glycaemic targets with subcutaneous (SC) insulin treatment, continuous intraperitoneal (IP) insulin infusion is an third-line alternative. Previous studies demonstrate that continuous intraperitoneal insulin infusion (CIPII) using an implantable pump device improves glycaemic control and quality of life in patients with 'brittle' T1DM. Nevertheless, literature comparing IP and SC insulin treatment is scarce. The primary objective of this study is to compare the effects of IP insulin delivery to SC insulin delivery.The null hypothesis (H0) of the current study holds inferiority of CIPII compared to SC insulin regarding long-term glycaemic control. The alternative hypothesis (H1) is the inverse: CIPII is non-inferior to SC insulin. In summary, H0: CIPII is inferior to the SC insulin treatment H1: CIPII is not inferior to SC insulin treatment This is an investigator initiated, open label and prospective matched-control study with a non-inferiority design. The trial duration is 36 weeks and is conducted in a single-centre (Isala Clinics, Zwolle). If non-inferiority is established superiority analyses are performed.

Official Title
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Intraperitoneal Insulin Administration as Alternative for Intensive Subcutaneous Insulin Therapy in Patients With Type 1 Diabetes Mellitus.

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Other: Mode of insulin administration


Participation Criteria
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Eligibility Criteria
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Case inclusion criteria T1DM If subjects are on CIPII, they must be included in (8) or If subjects are on CIPII, and didn't participate in (8), they must been on CIPII at start of the previous study (8) If subjects are on CIPII, they must been on CIPII for the past 4 years without interruptions (>30 days) Proper knowledge of the Dutch language. Case exclusion criteria Impaired renal function (plasma creatinine ≥150 µmol/L or glomerular filtration rate as estimated by the Cockcroft-Gault formula ≤50ml/min) Cardiac problems (unstable angina or myocardial infarction within the previous 12 months or New York Heart Association class III or IV congestive heart failure Mentally handicapped Current or past psychiatric treatment for schizophrenia Cognitive or bipolar disorder Current use or oral corticosteroids or suffering from a condition which necessitated oral or systemic corticosteroids use more than once in the previous 12 months Substance abuse, other than nicotine Current gravidity or plans to become pregnant during the trial Plans to engage in activities that require going >25 feet below sea level Any condition that the investigator and/or coordinating investigator feels would interfere with trial participation or evaluation of results. 4.4 Control inclusion criteria T1DM SC insulin as mode of insulin administration If subjects are on SC insulin, they must been on SC insulin for the past 4 years without interruption (>30 days) HbA1c at time of matching must be ≥7.0% (53mmol/mol) Proper knowledge of the Dutch language. Control exclusion criteria Impaired renal function (plasma creatinine ≥150 µmol/L or glomerular filtration rate as estimated by the Cockcroft-Gault formula ≤50ml/min) Cardiac problems (unstable angina or myocardial infarction within the previous 12 months or New York Heart Association class III or IV congestive heart failure Mentally handicapped Current or past psychiatric treatment for schizophrenia Cognitive or bipolar disorder Current use or oral corticosteroids or suffering from a condition which necessitated oral or systemic corticosteroids use more than once in the previous 12 months Substance abuse, other than nicotine Current gravidity or plans to become pregnant during the trial Plans to engage in activities that require going >25 feet below sea level Any condition that the investigator and/or coordinating investigator feels would interfere with trial participation or evaluation of results.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IP insulin<br>Patients treated with continuous intraperitoneal insulin infusion using a implantable pump | Other: Mode of insulin administration<br>* There are no interventions in this observational study. Both treatment groups continue the mode of therapy the patient had before the start of the present study: continuous intraperitoneal insulin infusion with an implantable pump (MIP2007D) or subcutaneous insulin administration with multiple daily injections or continuous subcutaneous insulin infusion.<br>|
| SC insulin<br>Patients treated with subcutaneous insulin, both multiple daily injections and continuous subcutaneous insulin infusion | Other: Mode of insulin administration<br>* There are no interventions in this observational study. Both treatment groups continue the mode of therapy the patient had before the start of the present study: continuous intraperitoneal insulin infusion with an implantable pump (MIP2007D) or subcutaneous insulin administration with multiple daily injections or continuous subcutaneous insulin infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glycaemic regulation | HbA1c (mmol/mol) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage time spent in hypo/hyper- and euglycaemia during a 3-7 day 24-hour blood glucose profile using a continuous glucose measurement system (CGMS). |  | 6 months | 
| Hypoglycaemic episodes |  | 6 months | 
| Concentrations of IGF-1 and IGFBP |  | 6 months | 
| Total daily insulin dose. |  | 6 months | 
| Lipid spectrum |  | 6 months | 
| Health related quality of life |  | 6 months | 
| Diabetes related quality of life |  | 6 months | 
| Diabetes related distress |  | 6 months | 
| Diabetes related self care |  | 6 months | 
| Treatment satisfaction |  | 6 months | 
| body mass index |  | 6 months | 
| Blood pressure |  | 6 months | 
| Microvascular complications of diabetes |  | 6 months | 
| Macrovascular complications of diabetes |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus type 1, Intraperitoneal insulin administration, Subcutaneous insulin administration, Continuous intraperitoneal insulin infusion