Clinical trial NCT03334318: PERL Continuous Glucose Monitoring (CGM) Study
Official title: PERL (Preventing Early Renal Loss in Diabetes) Continuous Glucose Monitoring (CGM) Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetic Nephropathies
Lead sponsor: Joslin Diabetes Center
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
name: University of Minnesota
name: University of Colorado, Denver
name: University of Michigan
name: Northwestern University Feinberg School of Medicine
name: Albert Einstein College of Medicine
name: Washington University School of Medicine
name: University of Washington
name: Providence Medical Research Center
First posted: 2017-11-07
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants of the PERL Clinical Trial

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: iGFR at the end of the PERL trial
timeFrame: Week 164 of the PERL trial
Secondary outcomes:
measure: HbA1c at week 80 of the PERL trial
timeFrame: Week 80 of the PERL Trial
measure: HbA1c at week 96 of the PERL trial
timeFrame: Week 96 of the PERL Trial
measure: HbA1c at week 112 of the PERL trial
timeFrame: Week 112 of the PERL Trial
measure: HbA1c at week 128 of the PERL trial
timeFrame: Week 128 of the PERL Trial
measure: HbA1c at week 142 of the PERL trial
timeFrame: Week 142 of the PERL Trial
measure: HbA1c at week 156 of the PERL trial
timeFrame: Week 156 of the PERL Trial
measure: HbA1c at week 164 of the PERL trial
timeFrame: Week 164 of the PERL Trial
measure: Mean blood glucose
timeFrame: From week 80 to week 164 of the PERL trial
measure: CV (coefficient of variation) of blood glucose
timeFrame: From week 80 to week 164 of the PERL trial
measure: % time 70-180 mg/dL
timeFrame: From week 80 to week 164 of the PERL trial
measure: % time below 54 mg/dL
timeFrame: From week 80 to week 164 of the PERL trial
measure: % time above 180 mg/dL
timeFrame: From week 80 to week 164 of the PERL trial
measure: % time above 250 mg/dL
timeFrame: From week 80 to week 164 of the PERL trial
measure: MAGE (Mean amplitude of glucose excursions)
timeFrame: From week 80 to week 164 of the PERL trial
measure: LBGI (Low blood glucose index)
timeFrame: From week 80 to week 164 of the PERL trial
measure: HBGI (High blood glucose index)
timeFrame: From week 80 to week 164 of the PERL trial
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center / University of Colorado Denver
state: Colorado
city: Atlanta
country: United States
facility: Emory University - Grady Memorial Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Brehm Center for Diabetes Research / University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein College of Medicine / Montefiore Medical Center
state: New York
city: New York
country: United States
facility: ICAHN School of Medicine at Mount Sinai
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Dallas
country: United States
facility: UT Southwestern Dallas
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Calgary
country: Canada
facility: Unversity of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: Joslin Diabetes Center
name: Alessandro Doria, MD PhD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Irl Hirsch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University, St. Louis, MO
name: Janet McGill, MD
role: PRINCIPAL_INVESTIGATOR
References: