PERL Continuous Glucose Monitoring (CGM) Study

Purpose

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.

Condition

  • Diabetic Nephropathies

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

NCT ID
NCT03334318
Status
Active, not recruiting
Sponsor
Joslin Diabetes Center

Study Contact

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.