Renal Mechanism of SGLT2 Inhibition

Launched by UNIVERSITY OF COLORADO, DENVER · Aug 17, 2022

Keywords

ClinConnect Summary

This clinical trial is studying how a medication called canagliflozin helps protect the kidneys in adults with type 2 diabetes. Canagliflozin is already used to help manage blood sugar levels and has been shown to benefit the heart, kidneys, and blood vessels. However, scientists want to better understand exactly how this drug works to prevent kidney damage in people with diabetes. To do this, the study will use advanced kidney imaging, small kidney tissue samples (biopsies), and detailed kidney function tests.

Adults aged 18 to 80 with type 2 diabetes for at least three years and mild to moderate kidney problems may be eligible to join. Participants need to have certain levels of kidney function and protein in their urine, and must be willing to take part after learning about the study. Those already taking certain other diabetes medications may also join if they’ve been on stable doses. During the study, participants will undergo kidney scans, biopsies, and special tests to measure how their kidneys work. Women who are pregnant or planning pregnancy won’t be eligible, and people with certain health conditions or allergies may not qualify. This trial aims to help doctors better understand how canagliflozin protects the kidneys, potentially improving care for people with diabetes in the future.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• Exclusion Criteria:
• • 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
• • Kidney cortex \<1 cm (both kidneys)
• • Kidney length \<8 cm (both kidneys)