Mechanism of SGLT2 Inhibition in the Kidney

NCT06291155 | Recruiting Phase 4 FDA Drug

• 1 other identifier: HUM00222335
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open-label, non-randomized clinical trial is to determine what effects, if any, an FDA-approved drug class known as SGLT2 inhibitors (Canagliflozin or INVOKANA) has any protective effects on kidney function in Type 2 diabetes. We are looking for participants 18-80 years of age, who have had a clinical diagnosis of Type 2 diabetes for ≥ 3 years. Participants will be asked to sign a consent and complete a screening visit prior to study entry including the following procedures for this study: Consent and Screening:

• Laboratory tests to determine baseline health
• Ultrasound to measure kidney size and ensure presence of 2 functioning kidneys Month 0:
• Study entry kidney MRI (day 0)
• Study entry kidney biopsy (within 30 days of MRI)
• Study entry visit for dispensing 100 mg/daily Canagliflozin medication 3 month supply Month 3:
• Study visit to dispense remaining 3 months of 100 mg/daily Canagliflozin medication
• Review of systems Month 6:
• Follow-up kidney MRI
• Follow-up kidney biopsy Study participants will also be requested to provide blood and urine samples for biobanking purposes. They will also be provided the opportunity to provide a stool sample at two time points, as well as the option to participate in a related study collecting samples to create induced Pluripotent Stem Cells (iPSCs). Participants will be compensated for their time and loss of work time, additionally, a nominal additional compensation for optional stool and iPSC samples.

Conditions

Type 2 Diabetes; Diabetic Kidney Disease

Keywords

Kidney biopsy; Kidney MRI; SGLT2 inhibitor; SGLT2i; FDA-approved; Renal biopsy; Renal MRI; Type 2 diabetes; Canagliflozin; INVOKANA

Outcome Measures

Primary Outcomes (1)

• Glomerular basement membrane (GBM) width and mesangial expansion

  Measured by morphometric examination of kidney tissue

  Baseline and 6 months

Secondary Outcomes (1)

• Kidney Transcript Changes

  6 month follow-up

Study Arms (1)

SGLT2i Arm

OTHER

Drug: SGLT2 inhibitor

Interventions

SGLT2 inhibitor DRUG

All participants will be receive 100 mg/daily doses of Canagliflozin (INVOKANA) for 6 months. Canagliflozin is a Sodium-glucose cotransporter 2 (SGLT2) inhibitor

Also known as: Canagliflozin, Invokana

SGLT2i Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-80 years.
• The lower age limit was set so renal function test results would not reflect changes associated with growth.
• Diagnosis of type 2 diabetes for ≥ 3 years.
• Estimated GFR \>45 and \< 90 ml/min/1.73m2 as determined from the CKD-EPI equation using serum creatinine (Levey et al., 2009)
• A screening urinary albumin-to-creatinine ratio \<3000 mg/g.
• Willingness to participate after receiving a thorough explanation of the study.
• Participants receiving a RAAS inhibitor must have been receiving the drug at maximum tolerable dose for at least 3 months prior to the study baseline examination.
• Participants receiving a GLP-1 receptor agonist must have been receiving the drug for at least 3 months prior to the study baseline examination.
• Participants must meet the current clinical guidelines for prescribing SGLT2 inhibitors, to maintain FDA-approved standards

You may not qualify if:

• Clinically significant disorders of the liver \[cirrhosis, portal hypertension, hepatitis, increased bilirubin (≥1.5 mg/dl), active or uncontrolled cardiovascular disease, symptomatic peripheral vascular disease, (i.e. intermittent claudication), pulmonary diseases (including uncontrolled asthma and restrictive or obstructive lung disease requiring therapy), renal-urinary disorders (calculi, urinary tract obstruction, glomerulonephritis, chronic infection), gastrointestinal disorders (nausea, vomiting, diarrhea or anorexia sufficient to cause weight loss or wasting), or hematocrit levels ≤30 percent in women or ≤35 percent in men.
• Prior and ongoing treatment with SGLT2 inhibitors
• Renovascular or malignant hypertension; uncontrolled hypertension (systolic blood pressure ≥150 or diastolic ≥90 mm Hg)
• Hematuria of unknown etiology.
• Prior to entry into the study, any participant with hematuria should be evaluated, the etiology established and documented, and treatment rendered as appropriate.
• Chronic debilitating disorders with or without treatment (e.g., systemic lupus erythematosus \[SLE\], cancer, amyloidosis, and chronic infection) that would interfere with the assessment of kidney function or that might reduce the chances of survival for a sufficient length of time to evaluate the efficacy of treatment.
• Currently receiving a drug regimen that includes steroids, immunosuppressants, or investigational new drugs not associated with this trial.
• Pregnancy.
• SGLT2 inhibitors are not recommended during the second or third trimester of pregnancy. Moreover, we do not wish to expose pregnant women to conscious sedation that is used during the kidney biopsies.. Women of childbearing potential must have a negative pregnancy test prior to entry and every 2 months during the study and agree to using an effective form of contraception throughout the study, such as the oral contraceptive pill or an intrauterine device. Women who are planning a pregnancy in the next three years will be excluded.
• Known hypersensitivity to canagliflozin or iodine.
• Bleeding disorders or requirements for anticoagulation or platelet inhibitors which cannot be safely interrupted since kidney biopsies cannot be performed safely in these individuals.
• Massive obesity with body mass index ≥45 kg/m².
• Kidney biopsies are more technically difficult with massive obesity.
• Allergy to iodine-containing contrast material or shellfish.
• Non-diabetic kidney disease - based on clinical history or kidney biopsy examination.

Sponsors & Collaborators

• University of Michigan: lead
• University of Colorado, Denver: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies

Interventions

Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Markus Bitzer, MD

  Professor of Internal Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chrysta C Lienczewski, BS

CONTACT

734-615-5021; boridley@umich.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine

Model Details: This is an open-label, non-randomized mechanistic trial of an FDA-approved drug

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 4, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)