Mechanism of SGLT2 Inhibition in the Kidney
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-80
SponsorUniversity of Michigan
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
SGLT2 inhibitor
DrugAll participants will be receive 100 mg/daily doses of Canagliflozin (INVOKANA) for 6 months. Canagliflozin is a Sodium-glucose cotransporter 2 (SGLT2) inhibitor
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: SGLT2i ArmOther 1 intervention
Trial outcomes
Primary outcomes
1
Glomerular basement membrane (GBM) width and mesangial expansion
Measured by morphometric examination of kidney tissue
Time frame
Baseline and 6 monthsSecondary outcomes
1
Kidney Transcript Changes
Molecular changes measured by change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens
Time frame
6 month follow-upSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Michigan
Lead sponsor
University of Colorado, Denver
Collaborator
Source ClinicalTrials.gov