Study Comparing Effectiveness of Intraperitoneal Insulin Administration to Subcutaneous Insulin Administration

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of insulin delivered in the peritoneum (abdomen)by an implantable pump in Type 1 diabetics.

Detailed Description
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Implantable insulin delivery pumps have been shown to reduce the occurrence of severe hypoglycemia in Type 1 DM subjects, as demonstrated in numerous European studies. Glycemic control is difficult to attain in subjects using exogenous insulin due to the risk of severe hypoglycemia. This study is aimed at comparing the efficacy of intraperitoneal (IP) insulin therapy to intensive subcutaneous insulin therapy over a period of 12 months.

Official Title
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A Randomized, Active Control, Multi-Center Study Comparing the Effect of Intraperitoneal Insulin Administration to Subcutaneous Insulin Administration on Glycemic Control and the Frequency of Severe Hypoglycemia

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Medtronic MiniMed Implantable Pump Human Recombinant Insulin
* Device: Medtronic MiniMed Implantable Pump System
* Drug: Aventis HOE21PH U400


Participation Criteria
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Eligibility Criteria
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Type 1 diabetes mellitus (American Diabetes Association definition) HbA1c greater than or equal to 7.5% Intensive insulin treatment for at least 3 months Physical and intellectual ability to operate MIP system Subject has been under the routine care of the investigator for at least two months prior to enrollment Subject has a reliable support person (defined as a person who has daily contact with the subject and knows whom to contact in the event of an emergency). Capability and willingness to perform self-monitoring of blood glucose at least four times daily for 9 months of the study and 7 times daily for 3 months of the study Physical and intellectual ability to operate the MIP system and to comply with the data reporting requirements of the study. Subject is willing to sign the informed consent form (approved by local Institutional Review Board and Medtronic MiniMed) Exclusion Criteria: The subject's insulin usage exceeds 66 units per day. Severe complications such as advanced autonomic neuropathy, legal blindness, or symptomatic cardiovascular disease as evidenced by a cardiovascular episode within the last six months Reside at or plan to travel to elevations above 8000 feet during the study period (commercial airline travel is acceptable) Subject who is pregnant, of childbearing potential or lactating and is neither surgically sterile, using contraceptives (devices, oral or implanted) nor other physician approved contraceptive The subject has any major concomitant disease or any physical or psychological disorder within the last five years, which might be considered life threatening, or which might confound the collection or interpretation of the study data The subject has previously enrolled in or participated in an investigational drug or device study within the preceding 4 weeks The subject has any condition that precludes him/her from completing the study requirements Has plans for activities which require them to go 25 feet below sea level

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MiniMed Implantable insulin Pump (MIP)<br>The experimental group will receive intraperitoneally (IP) delivered insulin via the Medtronic MiniMed Implantable Pump (MIP). At the time of implant, the pump will be filled with Aventis HOE21PH U400 insulin and the subject will be treated with this insulin for the first 180 days post implant. During the refill procedure performed 180 days post implant, any insulin remaining in the pump will be removed and the pump will be refilled with Medtronic MiniMed Implantable Pump Human Recombinant Insulin. | Drug: Medtronic MiniMed Implantable Pump Human Recombinant Insulin<br>* 400 IU per ml - dosage based on the Investigators clinical judgement and the individual subject requirements.<br>* Other names: Human insulin injection (rDNA origin);Device: Medtronic MiniMed Implantable Pump System<br>* The implantable pump system is intended to provide continuous intraperitoneal delivery of insulin in subjects with diabetes.<br>* Other names: IP insulin pump system;Drug: Aventis HOE21PH U400<br>* 400 IU per ml - dosage based on the Investigators clinical judgement and the individual subject requirements.<br>* Other names: Aventis ETP Insulin;|
| No Intervention: Subcutaneous insulin arm (SC)<br>The control group will remain on their current pre-study subcutaneous insulin therapy of either Multiple Daily Injections (MDI) or Continuous Subcutaneous Insulin Infusion (CSII - external insulin pump). The SC group will not be restricted to the type of insulin used, or be required to change or modify their current diabetes therapy for the purpose of the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c and Compared Between Groups | To determine whether Intra Peritoneal insulin delivery via MIP results in glycemic control that is equal to or superior (i.e. not inferior to) control with SC therapy (Ho : μ (IP) -μ (SC) ≥ 0.50% A1C), a repeated measures analysis of variance, adjusting for baseline A1C using SAS Proc Mixed was used to compare average A1C trends over time between the two treatment groups (19). Type 3 Least Square (LS) means for each group were assessed. The Estimate statement within SAS proc mixed was used to estimate contrasts among the LS means and confidence intervals for the contrasts. | Baseline and 12 months | 
| Incidence of Severe Hypoglycemia Events | The total number of severe hypoglycemia events, defined as a clinical episode of hypoglycemia (resulting in seizure or coma, requiring hospitalization, intravenous glucose or glucagon administration), or any hypoglycemia that requires assistance from another person, compared between the two study arms from Baseline to 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Daily Blood Glucose | For each subject, a minimum of two blood glucose readings per day was required for calculation of the average daily mean. The overall mean of the mean for each subject for the measure time frame was then calculated. The mean of the results for all subjects in each group were then analyzed and compared between groups both at Baseline and 12 months. | average from baseline to 12 months | 
| Mean Amplitude of Glycemic Excursions (MAGE) | MAGE was calculated by taking the arithmetic mean of BG excursions when both ascending and descending segments of the curve exceed one Standard Deviation of the average 24-hour BG value. MAGE was calculated for each subject using SMBG data from periods in which subjects had a minimum of 4 and maximum of 10 readings daily. The overall mean of the mean for each subject for the measure time frame was then calculated. The mean of the results for all subjects in each group were then analyzed and compared between groups both at Baseline and 12 months. | average from baseline to 12 months | 
| Low Blood Glucose Index (LBGI); | 4 to 10 daily blood glucose readings (BG) were required for this measure. LBGI was calculated from BG values collected for 30 days prior to Visit 2 and 30 days following Visits 5 and 7. The continuous measure was compared between the two treatment groups for the three periods with a repeated measures ANOVA using proc mixed. Type 3 least square means for each group were assessed and estimate statements used to make comparisons among the LS means and create confidence intervals on the contrasts. | average from baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Implantable Insulin Pump, Intraperitoneal Insulin Delivery