CANDY-CANE: Continuous Glucose Monitoring to Assess Glycemia in Chronic Kidney Disease - Changing Glucose Management

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT02608177
• Collaborator: American Diabetes Association (Other), Medtronic (Industry), Abbott (Industry)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The goal of this study is to test whether a dipeptidyl peptidase-4 inhibitor, compared with a sulfonylurea, improves time in normal blood glucose range and reduces blood glucose variability. Blood glucose is measured using a continuous glucose monitoring device.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases; Type 2 Diabetes	Drug: Linagliptin; Drug: Glipizide	N/A

Detailed Description

This is a proof-of-concept clinical trial testing the effects of linagliptin versus glipizide on glucose variability among people with type 2 diabetes and stage 3-4 CKD. In a cross-over design, each enrolled participant will receive 28 days of each study medication. Study medications will be provided in a randomly assigned order without blinding. The primary study outcome is glucose time in range, measured by blinded continuous glucose monitoring for the last 6 days of each 28-day treatment period. Secondary outcomes include indices of glycemic variability, hypoglycemia, and biomarkers of systemic inflammation, oxidative stress, and albuminuria. The overall goal of this research is to identify safe and effective treatments to control glycemia among patients with diabetes and CKD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Continuous Glucose Monitoring to Assess Glycemia in Chronic Kidney Disease - Changing Glucose Management
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Linagliptin/Glipizide Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide	Drug: Linagliptin; Receives 4 weeks of study drug linagliptin; Drug: Glipizide; Receives 4 weeks of study drug glipizide
Experimental: Glipizide/Linagliptin Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin	Drug: Linagliptin; Receives 4 weeks of study drug linagliptin; Drug: Glipizide; Receives 4 weeks of study drug glipizide

Outcome Measures

Primary Outcome Measures

1. Glucose Time in Range [last 6 days of each 28-day treatment period]

   Time with glucose 70-140 mg/dL

Secondary Outcome Measures

1. Glycemic Variability [last 6 days of each 28-day treatment period]

   SD of glucose readings

2. Hypoglycemia [last 6 days of each 28-day treatment period]

   Glucose <70 mg/dL for at least 10 minutes

3. Biomarkers of Systemic Inflammation [last 6 days of each 28-day treatment period]

   Measured by plasma C-reactive protein (CRP)

4. Biomarkers of Systemic Inflammation [last 6 days of each 28-day treatment period]

   Measured by plasma interleukin-6

5. Biomarkers of Oxidative Stress [last 6 days of each 28-day treatment period]

   Measured by plasma F2-isoprostanes

6. Biomarkers of Oxidative Stress [last 6 days of each 28-day treatment period]

   Measured by urine F2-isoprostanes

7. Biomarkers of Albuminuria [last 6 days of each 28-day treatment period]

   Measured by albumin-creatinine ratio

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes

• eGFR 15-59 mL/min/1.73 m2

• Hemoglobin A1c < 8%

• Age ≥ 18 years

• Current use of sulfonylurea

Exclusion Criteria:

• BMI > 40 kg/m2

• Actively using CGM for clinical care

• End stage renal disease needing dialysis

• Kidney transplant

• Pregnant or nursing

• Unable to provide informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Washington	Seattle	Washington	United States

Sponsors and Collaborators

• University of Washington
• American Diabetes Association
• Medtronic
• Abbott

Investigators

• Principal Investigator: Ian de Boer, MD, University of Washington

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 28, 2015

More Information

Publications

None provided.

• Responsible Party: Ian deBoer, Associate Professor, Medicine/Nephrology, University of Washington
• ClinicalTrials.gov Identifier: NCT02608177
• Other Study ID Numbers: 50084
• First Posted: Nov 18, 2015
• Last Update Posted: Oct 12, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Linagliptin; Glipizide

Study Results

Participant Flow

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin	Total
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Total of all reporting groups
Overall Participants	2	1	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.3 (9.9)	70.4 (NA)	68.3 (7.2)
Sex: Female, Male (Count of Participants)
Female	1 50%	0 0%	1 33.3%
Male	1 50%	1 100%	2 66.7%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic white race/ethnicity	2 100%	1 100%	3 100%
Region of Enrollment (Count of Participants)
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Glucose Time in Range
Description	Time with glucose 70-140 mg/dL
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glipizide	Linagliptin
Arm/Group Description	Outcome assessed among all participants in both treatment groups at the end of treatment with Glipizide for 4 weeks.	Outcome assessed among all participants in both treatment groups at the end of treatment with Linagliptin for 4 weeks.
Measure Participants	3	3
Mean (Standard Deviation) [minutes per day]	495.2 (671.9)	573.3 (669.1)

2. Secondary Outcome

Title	Glycemic Variability
Description	SD of glucose readings
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glipizide	Linagliptin
Arm/Group Description	Outcome assessed among all participants in both treatment groups at the end of treatment with Glipizide for 4 weeks.	Outcome assessed among all participants in both treatment groups at the end of treatment with Linagliptin for 4 weeks.
Measure Participants	3	3
Mean (Standard Deviation) [mg/dL]	40.9 (16.1)	41.5 (22.7)

3. Secondary Outcome

Title	Hypoglycemia
Description	Glucose <70 mg/dL for at least 10 minutes
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glipizide	Linagliptin
Arm/Group Description	Outcome assessed among all participants in both treatment groups at the end of treatment with Glipizide for 4 weeks.	Outcome assessed among all participants in both treatment groups at the end of treatment with Linagliptin for 4 weeks.
Measure Participants	3	3
Number [events]	4	2

4. Secondary Outcome

Title	Biomarkers of Systemic Inflammation
Description	Measured by plasma C-reactive protein (CRP)
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

Labs not run due to small sample size.

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
Measure Participants	0	0

5. Secondary Outcome

Title	Biomarkers of Systemic Inflammation
Description	Measured by plasma interleukin-6
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

Labs not run due to small sample size.

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
Measure Participants	0	0

6. Secondary Outcome

Title	Biomarkers of Oxidative Stress
Description	Measured by plasma F2-isoprostanes
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

Labs not run due to small sample size.

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
Measure Participants	0	0

7. Secondary Outcome

Title	Biomarkers of Oxidative Stress
Description	Measured by urine F2-isoprostanes
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

Labs not run due to small sample size.

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
Measure Participants	0	0

8. Secondary Outcome

Title	Biomarkers of Albuminuria
Description	Measured by albumin-creatinine ratio
Time Frame	last 6 days of each 28-day treatment period

Outcome Measure Data

Analysis Population Description

Labs not run due to small sample size.

Arm/Group Title	Linagliptin/Glipizide	Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide	Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
Measure Participants	0	0

Adverse Events

Time Frame	AE information collected over 8 weeks of the study
Arm/Group Title	Linagliptin/Glipizide		Glipizide/Linagliptin
Arm/Group Description	Arm receives 4 weeks of study drug linagliptin followed by 4 weeks of glipizide Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide		Arm receives 4 weeks of study drug glipizide followed by 4 weeks linagliptin Linagliptin: Receives 4 weeks of study drug linagliptin Glipizide: Receives 4 weeks of study drug glipizide
All Cause Mortality
	Linagliptin/Glipizide		Glipizide/Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	Linagliptin/Glipizide		Glipizide/Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Linagliptin/Glipizide		Glipizide/Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.