Renal Mechanism of SGLT2 Inhibition

NCT05507892 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-0668
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Canagliflozin is an oral drug which is currently approved for use in patients with type 2 diabetes by the US Food and Drug Administration (FDA). Canagliflozin acts by increasing salt and sugar loss in the urine, and has shown to protect heart, kidney, and blood vessel function in patients with type 2 diabetes. However, it is unknown how canagliflozin protects the kidneys from disease. Therefore, this study plans to learn more about how canagliflozin works to protect against diabetic kidney disease in adults with type 2 diabetes. This study will use state-of-the-art kidney imaging, kidney biopsies and detailed testing of kidney function to determine the mechanisms of protection afforded by canagliflozin.

Conditions

Type 2 Diabetes; Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• Glomerular basement membrane (GBM) width and mesangial expansion

  measured by morphometric examination of kidney tissue

  6 months

• Kidney Transcript Changes

  Molecular changes measured by change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens

  6 months

Secondary Outcomes (5)

• Cortical R2

  6 months

• Medullary R2

  6 months

• Renal Perfusion

  6 months

• Glomerular Filtration Rate (GFR)

  3 Hours

• Renal Plasma Flow (RPF)

  2.5 Hours

Study Arms (1)

Treatment

EXPERIMENTAL

Participants who will receive 100 mg of canagliflozin daily for six (6) months in addition to standard of care.

Drug: canagliflozin; Drug: Aminohippurate Sodium Inj 20%

Interventions

canagliflozin DRUG

Canagliflozin is in a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It is a used to treat type 2 diabetes. Canagliflozin lowers blood sugars by causing the kidneys to excrete more glucose in the urine.

Also known as: Invokana

Treatment

Aminohippurate Sodium Inj 20% DRUG

Diagnostic aid/agent used to measure renal plasma flow (RPF) PAH (Basic Pharma, Geleen, Netherlands) has been used to measure RPF in human research for 7 decades, and is very well tolerated and generally recognized as safe with low toxicity.

Also known as: -Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL -Para-aminohippurate

Treatment

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.

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 treatment with SGLT2 inhibitors and unable to perform a wash-out.
• 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 or to the intravenous filtration markers iohexol and p-aminohippurate needed for the renal clearance studies. 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.
• History of osteoporotic fracture.
• Conditions likely to interfere with informed consent or compliance with the protocol.
• Single kidney; any condition with a single kidney

Sponsors & Collaborators

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

Study Sites (2)

University of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies

Interventions

Canagliflozin; p-Aminohippuric Acid

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)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Aminohippuric Acids; Hippurates; Benzamides; Amides; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Keto Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Petter Bjornstad, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Kendrick, MD, MPH

CONTACT

303-724-4837; Jessica.Kendrick@CUANSCHUTZ.EDU

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label non-randomized mechanistic trial. This trial will enroll 40 participants who will receive 100 mg of canagliflozin daily for six (6) months in addition to standard of care.

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 19, 2022
• Study Start: October 10, 2022
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)