Selecting Insulin Analogs for Closed-Loop Control Using Multiplex Pharmacokinetic Profiling

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Steven J. Russell, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01684943
First received: August 21, 2012
Last updated: May 11, 2016
Last verified: May 2016
  Purpose

The investigators are doing this research study to compare the pharmacokinetics (rate of absorption) of insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine (Apidra) within individual subjects.

Additionally, the investigators will perform a preliminary feasibility evaluation of a minimally invasive continuous insulin monitoring (CIM) device and its use to derive PK parameters in human subjects.


Condition Intervention Phase
Type 1 Diabetes
Other: Multiplex pharmacokinetic profiling
Other: Continuous insulin monitoring
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Selecting Insulin Analogs for Closed-Loop Control Using Multiplex Pharmacokinetic Profiling

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • For Multiplex PK profiling: Aggregate mean difference in tmax between the analog with greatest and the analog with the least value of tmax for individuals [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • For Continuous Insulin Monitoring: Agreement between plots of insulin concentration in the blood and plots of insulin concentration in the microdialysate vs. time by both the CIM lab-on-a-chip and by immunoassays performed on fractions of microdialysate [ Time Frame: 1 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Multiplex PK: Correlation between HbA1c at study entry and use of insulin analog with most favorable PK as an outpatient for subjects with a difference in tmax between analogs. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Subjects with a difference in tmax between analogs will be catagorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. Whether there is a difference between the median A1c between these three groups will be tested with the Kruskal-Wallis one-way analysis of variance test. In addition whether there is a difference in the fraction of subjects in these groups meeting their A1c goal of less than or equal to 7% (i.e. whether the analog choice and meeting the A1c target are independent) will be determined with the chi-square test.

  • Multiplex PK: Fraction of subjects with difference in tmax between the analog with greatest and the analog with the least value of tmax that is > 25% [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Multiplex PK: Correlation between HbA1c at study entry and use of insulin analog with tmax < 60 minutes as an outpatient vs. use of an insulin analog with tmax > 60 minutes as an outpatient. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Subjects with a difference in tmax between analogs will be catagorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax > 60 minutes. Whether there is a difference between the median A1c between these two groups will be tested with the heteroskedastic Student's t test.

  • Multiplex PK: Correlation between number of monthly self-reported or meter recorded incidents of hypoglycemia at study entry and use of insulin analog with best PK kinetics. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Subjects with a difference in tmax between analogs will be catagorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. Whether there is a difference between the number of hypoglycemic episodes per month between these three groups will be tested with the Kruskal-Wallis one-way analysis of variance test. In addition whether there is a difference in the fraction of subjects in these groups with less than or equal to two episodes of hypoglycemia a week (i.e. whether the analog choice and the frequency of hypoglycemia are independent) will be determined with the chi-square test.


Estimated Enrollment: 40
Study Start Date: July 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Multiplex pharmacokinetic profiling
Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin
Other: Multiplex pharmacokinetic profiling
Experimental: Continuous insulin monitoring
Continuous insulin monitoring of insulin lispro
Other: Continuous insulin monitoring

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 12 years or older with clinical type 1 diabetes for at least five years
  • Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins including insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra).
  • Ability to consume a sufficient amount of carbohydrates over 2-3 hours to cover 9 units of rapid acting insulin

Exclusion Criteria:

  • Unable to provide informed consent
  • Unable to comply with study procedures
  • Inadequate venous access as determined by study nurse or physician at time of screening.
  • Pregnancy
  • History of gastric banding, gastric bypass, or other gastrointestinal condition that may prevent a subject from consuming a normal sized meal
  • Hemoglobin <13.5 for men, < 12 for women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684943

Contacts
Contact: Courtney Balliro, RN, CDE (617)726-1242 CBALLIRO@PARTNERS.ORG
Contact: Debbie Mondesir, BS (617) 643-6702 DMONDESIR1@PARTNERS.ORG

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Courtney Balliro, RN, CDE    617-726-1242    CBALLIRO@PARTNERS.ORG   
Principal Investigator: Steven J Russell, MD, PhD         
Sponsors and Collaborators
Massachusetts General Hospital
  More Information

Responsible Party: Steven J. Russell, MD, PhD, Associate Professor, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01684943     History of Changes
Other Study ID Numbers: 2010P001005 
Study First Received: August 21, 2012
Last Updated: May 11, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Pharmacokinetics

Additional relevant MeSH terms:
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016