PERL Continuous Glucose Monitoring (CGM) Study

• Sponsor: Joslin Diabetes Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03334318
• Collaborator: The Leona M. and Harry B. Helmsley Charitable Trust (Other), University of Minnesota (Other), University of Colorado, Denver (Other), University of Michigan (Other), Feinberg School of Medicine, Northwestern University (Other), Albert Einstein College of Medicine (Other), Washington University School of Medicine (Other), University of Washington (Other), Providence Medical Research Center (Other)
• Enrollment: 175
• Locations: 19
• Actual Duration (Months): 51
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Nephropathies	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 Design

• Study Type: Observational
• Actual Enrollment: 175 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: PERL (Preventing Early Renal Loss in Diabetes) Continuous Glucose Monitoring (CGM) Study
• Actual Study Start Date: Oct 1, 2017
• Actual Primary Completion Date: Aug 31, 2019
• Actual Study Completion Date: Dec 31, 2021

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. iGFR at the end of the PERL trial [Week 164 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.

Secondary Outcome Measures

1. HbA1c at week 80 of the PERL trial [Week 80 of the PERL Trial]

   Hba1c value at week 80 of the PERL trial

2. HbA1c at week 96 of the PERL trial [Week 96 of the PERL Trial]

   Hba1c value at week 96 of the PERL trial

3. HbA1c at week 112 of the PERL trial [Week 112 of the PERL Trial]

   Hba1c value at week 112 of the PERL trial

4. HbA1c at week 128 of the PERL trial [Week 128 of the PERL Trial]

   Hba1c value at week 128 of the PERL trial

5. HbA1c at week 142 of the PERL trial [Week 142 of the PERL Trial]

   Hba1c value at week 142 of the PERL trial

6. HbA1c at week 156 of the PERL trial [Week 156 of the PERL Trial]

   Hba1c value at week 156 of the PERL trial

7. HbA1c at week 164 of the PERL trial [Week 164 of the PERL Trial]

   Hba1c value at week 164 of the PERL trial

8. Mean blood glucose [From week 80 to week 164 of the PERL trial]

   Mean of blood glucose values measured by continuous glucose monitoring

9. CV (coefficient of variation) of blood glucose [From week 80 to week 164 of the PERL trial]

   Coefficient of variation of blood glucose values measured by continuous glucose monitoring

10. % time 70-180 mg/dL [From week 80 to week 164 of the PERL trial]

    Percentage of time with blood glucose in the 70-180 mg/dL range (as measured by continuous glucose monitoring)

11. % time below 54 mg/dL [From week 80 to week 164 of the PERL trial]

    Percentage of time with blood glucose below 54 mg/dL (as measured by continuous glucose monitoring)

12. % time above 180 mg/dL [From week 80 to week 164 of the PERL trial]

    Percentage of time with blood glucose above 180 mg/dL (as measured by continuous glucose monitoring)

13. % time above 250 mg/dL [From week 80 to week 164 of the PERL trial]

    Percentage of time with blood glucose above 250 mg/dL (as measured by continuous glucose monitoring)

14. MAGE (Mean amplitude of glucose excursions) [From week 80 to week 164 of the PERL trial]

    Mean amplitude of glucose excursions as measured by continuous glucose monitoring

15. LBGI (Low blood glucose index) [From week 80 to week 164 of the PERL trial]

    Low blood glucose index based on blood glucose values measured by continuous glucose monitoring

16. HBGI (High blood glucose index) [From week 80 to week 164 of the PERL trial]

    High blood glucose index based on blood glucose values measured by continuous glucose monitoring

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Davis Center / University of Colorado Denver	Aurora	Colorado	United States	80045
2	Emory University - Grady Memorial Hospital	Atlanta	Georgia	United States	30303
3	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
4	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
5	Brehm Center for Diabetes Research / University of Michigan	Ann Arbor	Michigan	United States	48105
6	Henry Ford Health System	Detroit	Michigan	United States	48202
7	University of Minnesota	Minneapolis	Minnesota	United States	55455
8	Washington University	Saint Louis	Missouri	United States	63110
9	Albert Einstein College of Medicine / Montefiore Medical Center	Bronx	New York	United States	10461
10	ICAHN School of Medicine at Mount Sinai	New York	New York	United States	10029
11	SUNY Upstate Medical University	Syracuse	New York	United States	13210
12	UT Southwestern Dallas	Dallas	Texas	United States	75390
13	Virginia Mason Medical Center	Seattle	Washington	United States	98101
14	University of Washington	Seattle	Washington	United States	98105
15	Providence Sacred Heart Medical Center	Spokane	Washington	United States	99204
16	Unversity of Calgary	Calgary	Alberta	Canada	T2T 5C7
17	University of Alberta	Edmonton	Alberta	Canada	T6G2E1
18	BC Diabetes	Vancouver	British Columbia	Canada	V5Y 3W2
19	University of Toronto	Toronto	Ontario	Canada	M5T-3L9

Sponsors and Collaborators

• Joslin Diabetes Center
• The Leona M. and Harry B. Helmsley Charitable Trust
• University of Minnesota
• University of Colorado, Denver
• University of Michigan
• Feinberg School of Medicine, Northwestern University
• Albert Einstein College of Medicine
• Washington University School of Medicine
• University of Washington
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alessandro Doria, Senior Investigator, Joslin Diabetes Center
• ClinicalTrials.gov Identifier: NCT03334318
• Other Study ID Numbers: 2018PG-T1D014
• First Posted: Nov 7, 2017
• Last Update Posted: Mar 29, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetic Nephropathies; Allopurinol

Study Results

No Results Posted as of Mar 29, 2022