Effect of SGLT2i on Cardiovascular Biomarkers in Patients With Type 2 Diabetes and CKD Stage 3b-4

This is a prospective, observational study to assess the effect of SGLT2 inhibitors on surrogate markers of kidney and cardiovascular health in patients with stage 3b and 4 chronic kidney disease (CKD).

This study includes three clinic in person visits and weekly telephone visits for 12 weeks.

1. Recruit 28 patients with CKD stages 3b-4 and follow up for 12 weeks
2. Determine the effect of interventions on the primary outcome variable serum klotho measured by immunoprecipitation-immunoblot

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Kidney Disease, Chronic
• Intervention / Treatment: Drug: SGLT2 inhibitor

• Study Type: Observational
• Enrollment (Estimated): 28
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Robert Toto, MD; Phone Number: 214-645-8267; Email: robert.toto@utsouthwestern.edu
• Study Contact Backup: Name: Nancy Wang, Bachelor; Phone Number: 214-645-8240; Email: zhengnan.wang@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Nancy Wang, Bachelor; Phone Number: 214-645-8240; Email: zhengnan.wang@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient with type 2 diabetes mellitus and stage 3b-4 chronic kidney disease.

Description

Inclusion Criteria:

• 18-80 years of age
• All races and ethnicities
• All genders
• Type 2 diabetes mellitus
• History of hypertension defined as > 130 or > 80 mmHg or normotensive on pharmacologic therapy
• Estimated glomerular filtration rate (GFR) (CKD Epi equation) of 15-44 ml/min/1.73 m2 (Stages 3b-4 CKD)
• Urinary albumin creatinine ratio of > 200 mg/g <5000mg/g
• Ability of study participant or legally authorized representative to provide informed written consent
• Able to maintain stable dose of any vitamin D and any calcium supplements for 180 days post randomization.

Exclusion Criteria:

• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
• History of organ transplantation
• Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes (T1D)
• Active use of SGLT2 inhibitor
• History of persistent hypercalcemia (serum total Calcium > 10.5 mg/dl)
• Body mass index > 45 kg/m2
• Active on kidney transplant list
• Inability to provide informed consent
• Any condition outside the renal and cardiovascular disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement
• Active malignancy requiring treatment at the time of screening (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
• Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
• Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator or women who have a positive pregnancy test at enrolment or randomization or women who are breast-feeding
• Participation in another clinical study with an investigational product (IP) during the last month prior to Enrolment
• Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Patients who cannot complete the patient reported outcome (PRO) assessments can still participate in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Group 1: take prescribed SGLT2i after baseline visit.	Drug: SGLT2 inhibitor; Participants will ingest a standard dose of SGLT2i prescribed by the standard of care physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum klotho levels at 6 weeks	Change in serum klotho levels in participants with advanced Diabetic Kidney Disease (DKD) at 6 weeks are measured by immunoprecipitation-immunoblot.	Baseline, 6 weeks
Change in serum klotho levels at 12 week	Change in Serum klotho levels in participants with advanced Diabetic Kidney Disease (DKD) at 12 weeks are measured by immunoprecipitation-immunoblot.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum magnesium levels at 6 weeks	Mean change from baseline in serum magnesium levels at 6 weeks is measured. Serum magnesium levels are measured by measuring the level of magnesium in the blood.	Baseline, 6 weeks
Change in serum magnesium levels at 12 weeks	Mean change from baseline in serum magnesium levels at 12 weeks is measured. Serum magnesium levels are measured by measuring the level of magnesium in the blood.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Robert Toto, MD, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Kidney Diseases; Renal Insufficiency, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: STU-2021-0492

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