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Recruiting Phase 4

Mechanism of SGLT2 Inhibition in the Kidney

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About this study

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.

Condition
Type 2 Diabetes, Diabetic Kidney Disease
Tested
SGLT2 inhibitor
Sponsor
University of Michigan

Who can join

Age
18 to 80 years
Sex
All sexes
Healthy volunteers
Not accepted

Inclusion 12

  • Minimum age: 18 years
  • Maximum age: 80 years
  • Study condition: Type 2 Diabetes, Diabetic Kidney Disease
  • 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 31

  • 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
  • Inclusion possible after this has been obtained within range

Where

1 site, 1 recruiting

University of Michigan

Ann Arbor, Michigan, United States

Recruiting

Contact

Potential match only. Final eligibility is determined by the study team.