PERL Continuous Glucose Monitoring (CGM) Study

PERL (Preventing Early Renal Loss in Diabetes) Continuous Glucose Monitoring (CGM) Study

Seven-point capillary profiles have shown that mean glucose correlates with both diabetic retinopathy and nephropathy risk. However, there remains great controversy as to whether the degree of variability around mean glucose may also contribute to these microvascular complications. The PERL trial (NCT02017171), testing whether treatment with allopurinol can slow down kidney function loss in type 1 diabetes, provides a unique opportunity to assess the role of glycemic variability in the progression of diabetic kidney disease in individuals who already have mild to moderate kidney disease. By applying Continuous Glucose Monitoring (CGM) in the PERL Study population, the investigators will be able to better understand how metrics of glycemia (mean, time above and below range, and various measures of variability) are associated with renal outcomes in the PERL population as a whole, but also in important subgroups (e.g., albuminuric vs. normoalbuminuric subjects with ongoing GFR decline, allopurinol vs. placebo arms). The nvestigators also aim to obtain precise information on the range of blood glucose corresponding to any given HbA1c value in this population since previous studies generally excluded patients with renal disease.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathies
• Intervention / Treatment: Other: Mean blood glucose; Other: Blood glucose CV; Other: % time 70-180 mg/dL; Other: % time below 54 mg/dL; Other: % time above 180 mg/dL; Other: % time above 250 mg/dL; Other: MAGE (Mean amplitude of glucose excursions); Other: LBGI (Low Blood Glucose Index); Other: HBGI (High Blood Glucose Index); Drug: Allopurinol; Drug: Placebo

Detailed Description

Participants who consent to the study will have an Abbott Freestyle Libre Pro sensor placed on the back of their upper arm at their first PERL visit after this ancillary study has begun and at all subsequent PERL Visits. The sensor will be continuously worn by participants for 14 days. At the end of the 14 days, the sensor will be removed and mailed by the participant to the Coordinating center. Since subjects are at various stages of the PERL protocol, the number of remaining visits at which the CGM will be applied will vary among subjects.

STUDY AIMS

1. To assess the effect of glycemic variability, as measured by the coefficient of variation of CGM glucose (CV, the ratio of standard deviation and the mean of CGM glucose values), on the PERL renal functional endpoint (iohexol GFR at the end of study).
2. To assess the effect of other glycemic parameters measured by CGM (mean glucose, % time 70-180 mg/dL, % time below 54 mg/dL, % time below 70 mg/dL, % time above 180 mg/dL, % time above 250 mg/dL, mean amplitude of glucose excursions [MAGE], low blood glucose index [LBGI], high blood glucose index [HBGI]) on the PERL renal functional endpoint.
3. To assess the relationship between CGM-measured glycemic parameters and HbA1c at various levels of renal function.
4. To compare the effects of CGM metrics on the PERL renal endpoint and the corresponding effect of HbA1c.
5. To assess the effect of allopurinol treatment on all of the different glycemic metrics including HbA1c, CV, etc. and on their association with the PERL renal endpoint.

• Study Type: Observational
• Enrollment (Actual): 175

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Unversity of Calgary
    • Edmonton, Alberta, Canada, T6G2E1
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • BC Diabetes
  • Ontario
    • Toronto, Ontario, Canada, M5T-3L9
      • University of Toronto
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center / University of Colorado Denver
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University - Grady Memorial Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Brehm Center for Diabetes Research / University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine / Montefiore Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Dallas
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98105
      • University of Washington
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants of the PERL Clinical Trial

Description

Inclusion Criteria:

• Being an active participant in the PERL clinical trial

Exclusion Criteria:

• Having completed PERL Visit 16
• Pregnancy
• History of skin reactions in relation to the application of Abbott Freestyle Libre Pro

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Allopurinol-treated; Participants in the PERL Clinical Trial (NCT02017171) randomized to allopurinol	Other: Mean blood glucose; Mean of blood glucose values measures by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: Blood glucose CV; Coefficient of variation of blood glucose values measures by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time 70-180 mg/dL; Percent of time with blood glucose in the 70-180 mg/dL range as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time below 54 mg/dL; Percent of time with blood glucose below 54 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time above 180 mg/dL; Percent of time with blood glucose above 180 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time above 250 mg/dL; Percent of time with blood glucose above 250 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: MAGE (Mean amplitude of glucose excursions); Mean amplitude of glucose excursions as measured by continuous glucose monitoring as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: LBGI (Low Blood Glucose Index); Low blood glucose index as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: HBGI (High Blood Glucose Index); High blood glucose index as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Drug: Allopurinol; Oral allopurinol tablets administered in the PERL Clinical Trial
Placebo-treated; Participants in the PERL Clinical Trial (NCT02017171) randomized to placebo	Other: Mean blood glucose; Mean of blood glucose values measures by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: Blood glucose CV; Coefficient of variation of blood glucose values measures by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time 70-180 mg/dL; Percent of time with blood glucose in the 70-180 mg/dL range as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time below 54 mg/dL; Percent of time with blood glucose below 54 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time above 180 mg/dL; Percent of time with blood glucose above 180 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: % time above 250 mg/dL; Percent of time with blood glucose above 250 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: MAGE (Mean amplitude of glucose excursions); Mean amplitude of glucose excursions as measured by continuous glucose monitoring as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: LBGI (Low Blood Glucose Index); Low blood glucose index as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Other: HBGI (High Blood Glucose Index); High blood glucose index as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Drug: Placebo; Oral placebo tablets administered in the PERL Clinical Trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iGFR at the end of the PERL trial	Glomerular filtration rate (GFR) at the end of the PERL trial, measured by the plasma clearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.	Week 164 of the PERL trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c at week 80 of the PERL trial	Hba1c value at week 80 of the PERL trial	Week 80 of the PERL Trial
HbA1c at week 96 of the PERL trial	Hba1c value at week 96 of the PERL trial	Week 96 of the PERL Trial
HbA1c at week 112 of the PERL trial	Hba1c value at week 112 of the PERL trial	Week 112 of the PERL Trial
HbA1c at week 128 of the PERL trial	Hba1c value at week 128 of the PERL trial	Week 128 of the PERL Trial
HbA1c at week 142 of the PERL trial	Hba1c value at week 142 of the PERL trial	Week 142 of the PERL Trial
HbA1c at week 156 of the PERL trial	Hba1c value at week 156 of the PERL trial	Week 156 of the PERL Trial
HbA1c at week 164 of the PERL trial	Hba1c value at week 164 of the PERL trial	Week 164 of the PERL Trial
Mean blood glucose	Mean of blood glucose values measured by continuous glucose monitoring	From week 80 to week 164 of the PERL trial
CV (coefficient of variation) of blood glucose	Coefficient of variation of blood glucose values measured by continuous glucose monitoring	From week 80 to week 164 of the PERL trial
% time 70-180 mg/dL	Percentage of time with blood glucose in the 70-180 mg/dL range (as measured by continuous glucose monitoring)	From week 80 to week 164 of the PERL trial
% time below 54 mg/dL	Percentage of time with blood glucose below 54 mg/dL (as measured by continuous glucose monitoring)	From week 80 to week 164 of the PERL trial
% time above 180 mg/dL	Percentage of time with blood glucose above 180 mg/dL (as measured by continuous glucose monitoring)	From week 80 to week 164 of the PERL trial
% time above 250 mg/dL	Percentage of time with blood glucose above 250 mg/dL (as measured by continuous glucose monitoring)	From week 80 to week 164 of the PERL trial
MAGE (Mean amplitude of glucose excursions)	Mean amplitude of glucose excursions as measured by continuous glucose monitoring	From week 80 to week 164 of the PERL trial
LBGI (Low blood glucose index)	Low blood glucose index based on blood glucose values measured by continuous glucose monitoring	From week 80 to week 164 of the PERL trial
HBGI (High blood glucose index)	High blood glucose index based on blood glucose values measured by continuous glucose monitoring	From week 80 to week 164 of the PERL trial

Collaborators and Investigators

• Sponsor: Joslin Diabetes Center
• Collaborators: University of Colorado, Denver; Washington University School of Medicine; Albert Einstein College of Medicine; University of Michigan; University of Washington; University of Minnesota; Northwestern University Feinberg School of Medicine; The Leona M. and Harry B. Helmsley Charitable Trust; Providence Medical Research Center
• Investigators: Principal Investigator: Alessandro Doria, MD PhD MPH, Joslin Diabetes Center; Principal Investigator: Irl Hirsch, MD, University of Washington; Principal Investigator: Janet McGill, MD, Washington University, St. Louis, MO

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): August 31, 2019
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: 2018PG-T1D014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No