Monocytes in Subjects With Type 1 Diabetes and Chronic Kidney Disease

This is a cross-sectional study in patients with Type 1 diabetes (TID) and chronic kidney disease (CKD) to test if time in range (TIR) affects the degree of hyperglycemia required for monocyte activation, podocyte injury, and assess if monocyte activation is attenuated by glucagon-like peptide (GLP-1) agonist treatment ex vivo.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes (T1D); Chronic Kidney Disease(CKD)

Detailed Description

The monocyte response from patients with T1D CKD will be compared to monocytes from T1D subjects without CKD as a control. Potential subjects will be recruited from existing Cleveland Clinic patients or the community. The study will entail an initial phone screen followed by a formal screening visit to determine eligibility. Eligible subjects will return for a study visit within 4 weeks for a blood draw. There is no intervention. This will complete the study for subjects unless the investigators do not obtain enough monocytes from the initial blood draw to complete the requisite lab studies. If this occurs, the investigators will ask the patient to return for a repeat study visit. All endpoints evaluating monocyte and podocyte injury will be conducted in the lab ex vivo.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Andrea Debs; Phone Number: 216-445-8354; Email: debsa@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Andrea Debs; Phone Number: 216-445-8354; Email: debsa@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Type 1 Diabetes with or without chronic kidney disease.

Description

Inclusion Criteria:

1. T1D CKD subjects:

   1. Adults, males or females diagnosed with T1D
   2. Age 18-65 years
   3. Diagnosed with CKD (eGFR 60-90 ml/min/1.73 m2)
   4. Diagnosed with albuminuria (UACR 30-500 mg/g)
   5. On insulin injections or pump
   6. On CGM

   Based on baseline CGM metrics, the investigators will stratify subjects to 2 groups Group A (Lower TIR group): TIR<60%, A1c 7.5-9.5 Group B (Higher TIR group): TIR>70% A1c 5.0-7.0

2. Controls: T1D subjects without CKD

   1. Adults, males or females diagnosed with T1D
   2. Age 18-65 years
   3. No CKD (eGFR >90 ml/min/1.73 m2)
   4. No albuminuria (UACR <30 mg/g)
   5. On insulin injections or pump
   6. On CGM

Based on baseline CGM metrics, the investigators will stratify subjects to 2 groups Group A (Lower TIR group): TIR<60%, A1c 7.5-9.5 Group B (Higher TIR group): TIR>70% A1c 5.0-7.0

Exclusion Criteria:

1. Hemoglobin <9
2. On GLP-1 agonist or DPP4 inhibitor or sodium-glucose co-transporter-2 inhibitors use within 30 days
3. pregnancy or plans to become pregnant
4. On steroids
5. Diagnosed with cancer, immunosuppression/autoimmune conditions
6. Reported heavy alcohol use or recreational drug use
7. Any condition which jeopardizes patient safety or affects monocytes at physician's discretion

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with Type 1 Diabetes; Patients with Type 1 Diabetes with or without chronic kidney disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with proinflammatory monocytes by flow cytometry, higher ER stress, and cytokine levels after monocyte exposure to hyperglycemia compared to euglycemia for 6 hours.	Number of subjects with proinflammatory monocytes by flow cytometry, higher ER stress, and cytokine levels after monocyte exposure to hyperglycemia compared to euglycemia for 6 hours	monocyte response to varying glycemic exposure after 6 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with monocytes which induces higher podocyte injury after monocyte exposure to hyperglycemia compared to euglycemia for 6 hours.	Number of subjects with monocytes which induces higher podocyte injury after monocyte exposure to hyperglycemia compared to euglycemia for 6	monocyte response to varying glycemic exposure after 6 hrs

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Stanford University
• Investigators: Principal Investigator: Rong M Zhang, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 1; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 24-1015; K12DK133995 (U.S. NIH Grant/Contract)

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