Evaluation of Accu-Chek DiaPort, a Port System for Continuous Intraperitoneal Insulin Infusion, in Patients With Type I Diabetes

Study Overview
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Brief Summary
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The Accu-Chek DiaPort system enables continuous intraperitoneal insulin infusion (CIPII): that is, infusion of insulin into the peritoneal cavity using an Accu-Chek insulin pump and an infusion set. The Accu-Chek DiaPort consists of a metal body with a catheter that is placed in the abdomen. The opening of the port is raised above the surface of the skin about 5 millimeters, while a flower-shaped plate is placed under the skin, providing stability for the port. The port has been designed for those diabetics who cannot benefit fully from subcutaneous insulin infusion. The primary objective of the study is to assess the suitability of Accu-Chek DiaPort to perform continuous intraperitoneal insulin delivery. The data collection focuses on the condition of tissue around the port after the implantation, possible peritoneal reactions to the port system, and the peritoneal delivery of insulin. Secondary objectives are the assessments of therapeutic performance and successful implementation of design requirements. In total 12 Patients will participate in this open, mono-centre, single-arm, interventional clinical trial. The study lasts 9 months (without run in period of 3 to 1 week) separated in two parts. Phase I last 12 weeks. Phase II last 6 month until the end of the study. During the study, seven visits are planned. The screening visit can take place up to 3 weeks before study start. At the implantation visit which can last up to 5 days the port will be implanted. After the implantation insulin therapy will be adjusted for CIPII and the patients will be trained for handling and daily care of the Accu-Chek DiaPort system. To check the functionality of the system, the first control visit will take place 2 weeks and the second control visit 6 weeks after the implantation. At the week 12 visit, the most important parameters will be collected for the phase I report. The following visits take place 6 and 9 months after the implantation.

Official Title
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Evaluation of Accu-Chek DiaPort, a Port System for Continuous Intraperitoneal Insulin Infusion, in Patients With Type I Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Device: Accu-Chek DiaPort


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >= 18 years of age at the time of the screening visit Type 1 diabetes mellitus On CSII therapy for at least 6 months prior to the screening visit Has been unsuccessfully treated with standard subcutaneous insulin therapy including CSII therapy, as defined by frequent (defined as handicapping in daily life) or severe (needing help from a third party) hypoglycemia and/or HbA1c above 8.5%, and/or other medical indication for CIPII therapy Presence of at least one of the following indications for CIPII therapy: - Frequent (defined as handicapping daily life) hypoglycemia during CSII therapy - Severe hypoglycemia (needing help from a third party) during CSII therapy - HbA1c above 8.5% during CSII therapy - Hypoglycemia unawareness during CSII therapy - Real subcutaneous insulin resistance - Insulin-induced lipoatrophy - Insulin-associated lipohypertrophy not controlled by site rotation - Other skin disorders interfering with the subcutaneous route of administration - Marked fluctuations of glucose levels and insulin requirements during CSII therapy- History of allergies to materials required for subcutaneous insulin therapy Performs usually self-management of blood glucose at least 4 times per day Willing to adhere to the study visit schedule and motivated to undergo the therapy Exclusion Criteria: Presence of marked peritoneal adhesions or scarring after abdominal surgery Disorders of the gastrointestinal tract, respectively the digestive system potentially interfering with the intraperitoneal route of administration (e.g. presence of marked peritoneal adhesions, or colonic disease) Known high levels of anti-insulin antibodies History of allergy to materials used for the Accu-Chek DiaPort (titanium, polyethylene) Severely impaired immune response Uses systemic oral or inhaled steroids for > 14 days within the last 3 months Pregnant or lactating women, or women currently planning a pregnancy Previous history of severe chronic liver disease defined as signs of portal hypertension and/or Quick's value below 50% in spite of vitamin K administration Subject is treated for malignancy (chemotherapy, radiation or other treatment) (self-reported) Positive for HIV infection Is under CAPD treatment Suffers from severe eating disorders like bulimia or anorexia Alcohol or drug abuse Serious psychological disorders like schizophrenia, depression, Münchhausen's syndrome etc. Presence of known or suspected infections, bacteremia, septicemia or peritonitis Participation in a clinical trial (medicinal, medical device) within the last 30 days prior to screening

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Participants were implanted with Accu-Chek DiaPort with Infusion Set connected to an Accu-Chek Insulin Pump to perform continuous intraperitoneal insulin delivery. | Device: Accu-Chek DiaPort<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Suitability of the Device - Overall Suitability Score | Suitability of the device was assessed by the investigator using a questionnaire that determined the following: 1) condition of the tissue around the port: tight connection between port and skin (mechanical stability, dislocation of port, signs of redness/swelling, infection, or pain), 2) peritoneal reactions (persistent dull pain due to catheter, signs of infection/allergic reaction) and ability to deliver insulin intraperitonally at every visit after implantation. Suitability score was determined using participant's responses to a questionnaire where 1 equals (=) no problem, 2=minor/negligible problems, 3=some/noticeable problems, 4=major/cumbersome and 5=severe/almost unbearable problems. Each question was scored and an average across the questions was determined as an overall score. The scores ranged from 1 (not at all suitable) to 5 (completely suitable). | Week 12 | 
| Percentage of Participants With Problems Involving the Tight Connection Between Port and Skin | Mechanical stability of the device was determined by the stability of the ingrowth surrounding the port as determined by the physician. The ingrowth problems are categorized as follows: Category 1= complete stable Ingrowth, 2= Ingrowth working with negligible problems, 3= Ingrowth working with some problems, 4= Ingrowth working with major problems and 5= Ingrowth resulting in almost non-functional port. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants With Dislocation of Port | Position of the port was determined by the physician and was categorized as follows: Category 1= No dislocation; 2= Minimal dislocation; 3= Clearly visible dislocation, with minimal impairment of function; 4= Dislocation impairs functions; 5= Dislocation results in disabling functions. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants With Signs of Redness/Swelling in the Tissue Around the Port | Signs of Redness/Swelling was determined by the physician and was categorized as follows: Category 1= None; 2= Minor, negligible; 3= Some, noticeable; 4= Major; 5= Severe. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants With Signs of Infection in the Tissue Around the Port | Signs of infection were determined by the physician and categorized as follows : Category 1= None; 2= Minor, negligible; 3= Some, noticeable 4= Major; 5= Severe. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants With Signs of Pain in the Tissue Around the Port | Signs of pain was determined from the participant questionnaire which was categorized as follows: category 1= No pain; 2= Minor, negligible; 3= Some, noticeable; 4= Major, cumbersome; 5=Severe, almost unbearable. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants With Persistent Dull Pain Due to Catheter | Pain due to catheter was determined by a participant questionnaire and categorized as follows: Category 1= No pain; 2= Minor, negligible; 3= Some, noticeable; 4= Major, cumbersome; 5= Severe, almost unbearable. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants With Signs of Infection/Allergic Reaction at the Site of Implant | Signs of infection/allergic reaction at the site of implant was determined by the physician and categorized as follows: 1= No problems; 2= Minor problems; 3= Some problems; 4= Major problems and/or replacement of catheter necessary; 5= Severe problems and/or explanation of port necessary. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 
| Percentage of Participants Categorized by Ability of the Port to Deliver Insulin Intraperitonally | Problems in ability to deliver insulin intraperitoneally was determined by the physician and categorized as follows: 1= No problems; 2= Minor problems; 3= Some problems; 4= Major problems and/or replacement of catheter necessary; 5= Severe problems and/or explanation of port necessary. The percentage of participants in each category for the specified time point is presented. | Weeks 2 and 12 and Months 6, 9, 12 and 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Doses Dispensed From Insulin Pump | Total insulin dose (in international units per milliliter [IU/mL]) from pump was measured per day as mean per day measured over 7 days. | Screening, Week 12 and Months 6, 9 and 12 | 
| Hemoglobin A1c Levels | Glycated hemoglobin (HbA1c) is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. HbA1c levels are a measure of glycemic control. | Screening, Week 12 and Months 6, 9 and 12 | 
| Self Monitored Blood Glucose Levels | Participants monitored glucose levels on a daily basis and recorded for evaluation. Glucose levels are measured as milligrams per deciliter (mg/dL) | Screening, Week 12 and Months 6, 9 and 12 | 
| Continuous Glucose Measurement (CGM) - Glucose Levels | CGM measurements were performed using a diurnal CGM sensor and group means were calculated over 10 minute periods of the CGM measurements. | Screening, Week 12 and 6 Months | 
| Glycemic Variability: Percent Coefficient of Variation in Blood Glucose | Both self monitored (SMBG) and continuous (CGM) glucose measurements were used to determine the coefficient of variation in blood glucose. CGM data are only evaluated for a 1 week time period and are no direct comparison to the SMBG that reflect the full time frame between visits. | Screening, Week 12 and Months 6, 9 and 12 | 
| Percentage of Participants Achieving Target Glucose Levels | Target glucose values were 70-180 mg/dL. Participants with glucose levels below 70 mg/dL were considered to be under target and those above 180 mg/dL were considered over target. The mean of Glucose-Measurements at the visit date was calculated as follows: a variable was created for each category (within target [70-180 mg], below target and above target) that tells if the value lies within this category. Then the percentage per participant and visit was calculated. The mean represents the mean of these percentages per participant at the visit. | Screening, Week 12 and 6 Months | 
| Design Validation Participant Questionnaire - Percentage of Participants With a Positive Response | The participant questionnaire consisted of two parts including description of routine operations, followed by 23 questions used to determine the following: percentage of participants needing consultation of instructions for use of fixation disc or infusion set; percentage of participants with pain after implantation, percentage of participants with moderate pain during 4 to 6 days after implantation, moderate pain for 7 days or more; percentage of participants with temporal disconnection from infusion set; percentage of participants with use of handling aid for temporal storage; percentage of participants with a reason for temporal disconnection of infusion set from port either sex, shower, or sport; percentage of participants changing fixation disc ≥3 days or infusion set ≥4 days and the cartridge, and percentage of participants cleaning the skin around the port daily, every second day, or every third to fifth day, either with saline during healing or with alcohol after healing. | Week 12 |