Back to resultsStudy Comparing Effectiveness of Intraperitoneal Insulin Administration to Subcutaneous Insulin Administration (MIP310)
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Medtronic MiniMed Implantable Pump Human Recombinant Insulin
Medtronic MiniMed Implantable Pump System
Aventis HOE21PH U400
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Diabetes, Implantable Insulin Pump, Intraperitoneal Insulin Delivery
Eligibility Criteria
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
Sites / Locations
- Sansum Medical Research Institute
- University of Colorado Health Sciences Center
- Hellman & Rosen Endocrine Associates
- Cleveland Clinic
- Diabetes & Glandular Disease Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
MiniMed Implantable insulin Pump (MIP)
Subcutaneous insulin arm (SC)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT00211536
First Posted
September 13, 2005
Last Updated
September 19, 2011
Sponsor
Medtronic Diabetes
1. Study Identification
Unique Protocol Identification Number
NCT00211536
Brief Title
Study Comparing Effectiveness of Intraperitoneal Insulin Administration to Subcutaneous Insulin Administration
Acronym
MIP310
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
June 2002 (undefined)
Primary Completion Date
August 2004 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medtronic Diabetes
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Diabetes, Implantable Insulin Pump, Intraperitoneal Insulin Delivery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MiniMed Implantable insulin Pump (MIP)
Arm Type
Experimental
Arm Description
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.
Arm Title
Subcutaneous insulin arm (SC)
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Medtronic MiniMed Implantable Pump Human Recombinant Insulin
Other Intervention Name(s)
Human insulin injection (rDNA origin)
Intervention Description
400 IU per ml - dosage based on the Investigators clinical judgement and the individual subject requirements.
Intervention Type
Device
Intervention Name(s)
Medtronic MiniMed Implantable Pump System
Other Intervention Name(s)
IP insulin pump system
Intervention Description
The implantable pump system is intended to provide continuous intraperitoneal delivery of insulin in subjects with diabetes.
Intervention Type
Drug
Intervention Name(s)
Aventis HOE21PH U400
Other Intervention Name(s)
Aventis U400 insulin, Aventis ETP Insulin
Intervention Description
400 IU per ml - dosage based on the Investigators clinical judgement and the individual subject requirements.
Primary Outcome Measure Information:
Title
Change in HbA1c and Compared Between Groups
Description
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.
Time Frame
Baseline and 12 months
Title
Incidence of Severe Hypoglycemia Events
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Average Daily Blood Glucose
Description
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.
Time Frame
average from baseline to 12 months
Title
Mean Amplitude of Glycemic Excursions (MAGE)
Description
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.
Time Frame
average from baseline to 12 months
Title
Low Blood Glucose Index (LBGI);
Description
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.
Time Frame
average from baseline to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott W Lee, MD
Organizational Affiliation
Medtronic
Official's Role
Study Director
Facility Information:
Facility Name
Sansum Medical Research Institute
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Facility Name
University of Colorado Health Sciences Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Hellman & Rosen Endocrine Associates
City
North Kansas City
State/Province
Missouri
ZIP/Postal Code
64116
Country
United States
Facility Name
Cleveland Clinic
City
Wooser
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Diabetes & Glandular Disease Clinic
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
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Study Comparing Effectiveness of Intraperitoneal Insulin Administration to Subcutaneous Insulin Administration
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