Effect of Closed Loop Glucose Control on Exercise-Associated Hypoglycemia (ePID-03)

• ClinicalTrials.gov Identifier: NCT00831389
• Recruitment Status: Completed
• First Posted: January 28, 2009
• Results First Posted: October 11, 2012
• Last Update Posted: December 12, 2017
• Sponsor: Medtronic Diabetes
• Collaborator: Juvenile Diabetes Research Foundation
• Information provided by (Responsible Party): Medtronic Diabetes

Tracking Information

• First Submitted Date: January 26, 2009
• First Posted Date: January 28, 2009
• Results First Submitted Date: June 8, 2012
• Results First Posted Date: October 11, 2012
• Last Update Posted Date: December 12, 2017
• Study Start Date: January 2009
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2012)

• Plasma Glucose (PG) Response to Exercise [ Time Frame: Begins at start of exercise, at or after 15:00 on the in-patient visit day randomly assigned each subject for exercise; ends at start of the subsequent meal. Median period: 121 minutes (min), interquartile range (IQR): 15 min, range: 93 to 133 min. ]
  PG at start of exercise minus the subsequent PG nadir
• Incidence of Hypoglycemia Immediately Following Exercise [ Time Frame: Begins at end of exercise, at or after 16:15 on the in-patient visit day randomly assigned each subject for exercise; ends at 22:00 of same day. Median period: 333 minutes (min), interquartile range (IQR): 28 min, range: 262 to 344 min. ]
  Tally of episodes where either plasma glucose (PG) < 60 mg/dL, or supplemental glucose was administered to prevent imminent PG < 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1.
• Incidence of Nocturnal Hypoglycemia Following Exercise [ Time Frame: Begins at 22:00 on the in-patient visit day randomly assigned each subject for exercise; ends at 6:00 of the subsequent day. Period was 480 minutes (min) for all subjects, both study phases. ]
  Tally of episodes where either plasma glucose (PG) < 60 mg/dL, or supplemental glucose was administered to prevent imminent PG < 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1.

• Original Primary Outcome Measures (submitted: January 26, 2009): Plasma glucose values (hypoglycemia, defined as reference blood glucose <60mg/dL). [ Time Frame: Incidence of hypoglycemia in the immediate post-exercise period and the night following exercise during closed-loop control will be compared with that of open-loop control. ]

Current Secondary Outcome Measures (submitted: September 10, 2012)

• Peak Post-prandial Plasma Glucose (PG) [ Time Frame: Union of 6 meal periods (3 per day on study days 2 & 3). A meal period runs from meal start to start of next meal, or 22:00 for 3rd meal of the day. Union of 6 periods median: 1666 minutes (min), interquartile range (IQR): 15 min, range: 1638 to 1680 min. ]
  For each subject and study phase, the six peak PG following each of the six meals were determined. The median of these six peaks became the one peak post-prandial PG value representing each subject and study phase.
• Nadir Plasma Glucose (PG) Immediately Following Exercise [ Time Frame: Begins at start of exercise, at or after 15:00 on the in-patient visit day randomly assigned each subject for exercise; ends at start of the subsequent meal. Median period: 121 minutes (min), interquartile range (IQR): 15 min, range: 93 to 133 min. ]
  The PG nadir observed following the start of exercise
• Overnight Nadir Plasma Glucose (PG) [ Time Frame: Union of the two 8-hour overnight periods beginning at 22:00 on in-patient visit days 2 & 3, ending at 6:00 on the subsequent day. The union of the two periods was 960 minutes (min) for all subjects, both study phases. ]
  For each subject and study phase, the overnight nadir PG for each of two nights were determined. The mean of these two nadirs became the one nadir overnight PG value representing each subject and study phase.
• Percentage of Time Plasma Glucose (PG) is Within the Euglycemic Range. [ Time Frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total. ]
  For each subject and arm, the percentage of the PG curve such that 70 <= PG curve <= 180 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals.
• Percentage of Time Plasma Glucose (PG) is Above the Euglycemic Range. [ Time Frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total. ]
  For each subject and study phase, the percentage of the PG curve > 180 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals.
• Percentage of Time Plasma Glucose (PG) is Below the Euglycemic Range. [ Time Frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total. ]
  For each subject and study phase, the percentage of the PG curve < 70 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals.

• Original Secondary Outcome Measures (submitted: January 26, 2009): Glycemic control, assessed by mean glucose level, percentage of glucose levels within target range, peak postprandial levels, and nadir glucose levels after exercise and overnight; and % of glucose levels below target range and above target range [ Time Frame: after exercise and overnight ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Closed Loop Glucose Control on Exercise-Associated Hypoglycemia
• Official Title: Effect of Closed Loop Glucose Control on Exercise-Associated Hypoglycemia
• Brief Summary: The purpose of the study is to compare the glycemic control during and following aerobic exercise using either an open or closed-loop insulin delivery system.
• Detailed Description: This is an open-label, single-center, randomized crossover study evaluating the performance of a closed-loop insulin delivery system using a subcutaneous glucose sensor and an external insulin pump and comparing it to an open-loop delivery system during aerobic exercise. Subject participation will be for a maximum of 16 weeks including an outpatient study (up to 6 days) and two inpatient studies (one closed-loop; the other open-loop). The closed- and open-loop visit consists of approximately 67 hours over 4 days and 3 nights.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Type 1 Diabetes Mellitus

Intervention

Device: Closed Loop

Insulin pump controlled by closed loop unit and algorithm

Study Arms

• Experimental: Closed Loop (CL) Phase
  Closed Loop (CL) Phase
  Intervention: Device: Closed Loop
• No Intervention: Standard of Care (OL) Phase
  Standard of Care (OL) Phase or Open Loop Phase

• Publications *: Sherr JL, Cengiz E, Palerm CC, Clark B, Kurtz N, Roy A, Carria L, Cantwell M, Tamborlane WV, Weinzimer SA. Reduced hypoglycemia and increased time in target using closed-loop insulin delivery during nights with or without antecedent afternoon exercise in type 1 diabetes. Diabetes Care. 2013 Oct;36(10):2909-14. doi: 10.2337/dc13-0010. Epub 2013 Jun 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 7, 2011): 13
• Original Estimated Enrollment (submitted: January 26, 2009): 26
• Actual Study Completion Date: November 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female subjects between 12-30 years of age.
• Subjects must weigh at least 50 kg to accommodate phlebotomy.
• Previously diagnosed Type 1 Diabetes Mellitus
• Diabetes duration at least 1 year.
• Currently treating their diabetes with an insulin pump.
• A1C of ≤ 9.0 % at time of enrollment.
• Willing to have an intravenous (IV) line inserted for frequent blood sampling and infusion of glucose if needed.
• Willing to wear two (2) subcutaneous glucose sensors and two (2) transmitters simultaneously during closed-loop portion of the study.
• Be in good general health without other acute or chronic illnesses except treated hypothyroidism or celiac disease and asthma not requiring glucocorticoid use.
• Able to tolerate a 75-minute exercise period of moderate intensity.
• Speak and understand English.
• Subject and parent (if minor) must be able to comprehend and sign the informed consent form and other study documents.

Exclusion Criteria:

• Pregnancy (urine pregnancy test) or lactation, if female.
• 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.
• Subject has a cardiac pacemaker or similar device that may be sensitive to radio frequency telemetry.

• Subject using any of the following medications:

  • glucocorticoids
  • cyclosporine
  • L-asparaginase
  • niacin
  • protease inhibitors
  • anti-psychotics
  • GnRH agonists
  • beta-blockers
  • calcium channel blockers
  • immunosuppressants
  • over-the-counter medications that may effect glucose metabolism.

• Subject has any of the following conditions

  • insulin allergy
  • severe insulin resistance
  • exercise-induced asthma
  • musculoskeletal problems that may impact ability to complete exercise protocol
  • substance abuse
  • skin ulcers or poor wound healing
  • bleeding disorders
  • chronic infections
  • eating disorders
  • give a history of or are predisposed to major stress
  • any other major organ system disease.
• Subject has experienced two (2) or more severe hypoglycemic events -seizures/coma requiring assistance in the past six (6) months.
• Subject has any other condition that in the investigator's opinion warrants exclusion from the study or precludes him/her from completing the protocol.
• Subjects using dietary supplements within 14 days of study enrollment
• Subject is currently enrolled in another study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 30 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00831389
• Other Study ID Numbers: ePID-03
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Medtronic Diabetes
• Study Sponsor: Medtronic Diabetes
• Collaborators: Juvenile Diabetes Research Foundation

Investigators

• Principal Investigator: Stuart Weinzimer, MD; Yale University

• PRS Account: Medtronic Diabetes
• Verification Date: November 2017