Effects of SGLT2 inhibitors on kidney function in Type 2 diabetes
Molecular Mechanisms of SGLT2 Inhibition in Diabetic Kidney Disease
This study is testing if the diabetes medication Canagliflozin can help protect kidney function in adults with Type 2 diabetes and early signs of kidney disease.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | University of Michigan Academic / other |
| Locations | 1 site (Ann Arbor, Michigan) |
| Trial ID | NCT06291155 on ClinicalTrials.gov |
What this trial studies
This open-label, non-randomized clinical trial aims to investigate the protective effects of the SGLT2 inhibitor Canagliflozin on kidney function in adults with Type 2 diabetes and early diabetic kidney disease. Participants aged 18-80 will receive 100 mg of Canagliflozin daily for six months, alongside standard care. The study will assess changes in kidney function through kidney biopsies and MRIs, focusing on energy metabolism and structural progression of kidney disease. Primary outcomes include changes in intrarenal transcripts and secondary outcomes involve glomerular filtration rate and renal plasma flow measurements.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-80 with a clinical diagnosis of Type 2 diabetes for at least three years and specific kidney function criteria.
Not a fit: Patients with significant liver disorders or those not meeting the eligibility criteria for SGLT2 inhibitors may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide insights into how SGLT2 inhibitors can protect kidney function in patients with Type 2 diabetes.
How similar studies have performed: Other studies have shown promising results with SGLT2 inhibitors in improving kidney outcomes, suggesting this approach is supported by existing evidence.
Eligibility criteria
Show full inclusion / exclusion 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. * Participants must meet the current clinical guidelines for prescribing SGLT2 inhibitors, to maintain FDA-approved standards 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 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. * History of osteoporotic fracture. * History of lower-limb amputation irrespective of etiology * Conditions likely to interfere with informed consent or compliance with the protocol. * Known solitary kidney * Size of one or both kidneys on ultrasound \< 9 cm (small kidney size is concerning for renal atrophy due to underlying kidney disease) or \> 2 cm discrepancy between left and right kidney sizes based on largest longitudinal diameter * Current use of UGT enzyme inducters, lithium, and digoxin * Blood urea nitrogen (BUN) \> 80 gm/dL * INR \> 1.4 (a) * PTT \> 35 seconds (a) * Platelet count \< 100,000 uL (a) * Hemoglobin (Hgb) \< 10 mg/dL (a) * Hydronephrosis or other important renal ultrasound findings such as significant stone disease 1. Inclusion possible after this has been obtained within range
Where this trial is running
Ann Arbor, Michigan
- University of Michigan — Ann Arbor, Michigan, United States (Recruiting)
Study contacts
- Principal investigator: Markus Bitzer, MD — Professor of Internal Medicine
- Study coordinator: Chrysta C Lienczewski, BS
- Email: boridley@umich.edu
- Phone: 734-615-5021
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.