Type 2 DiabetesPhase 4NCT06291155
Mechanism of SGLT2 Inhibition in the Kidney
A Phase 4 study testing SGLT2 inhibitor in people with Type 2 Diabetes and Diabetic Kidney Disease, run by University of Michigan at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Type 2 Diabetes, Diabetic Kidney Disease
- What is being tested?
- SGLT2 inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2024to 28 Feb 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Chrysta C Lienczewski, BS, 734-615-5021, boridley@umich.edu
Markus Bitzer, MD
About this study
Official title: Molecular Mechanisms of SGLT2 Inhibition in Diabetic Kidney Disease
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:
Read more
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.
Read the detailed description
The purpose of this protocol is to examine the effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin on intrarenal transcripts of energy metabolism in adults with type 2 diabetes and early diabetic kidney disease (DKD) via 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. The primary objective of this study is to determine whether canagliflozin affects intrarenal transcripts of energy metabolism in adults with type 2 diabetes and early DKD.
The primary outcomes measure will be change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens obtained at study entry and after 6 months of study drug. Secondary outcomes include assessing the effects of canagliflozin on structural progression of DKD assessed by morphometric examination of kidney tissue specimens from the paired research biopsies. Additional secondary outcomes include measures of glomerular filtration rate (GFR) and renal plasma flow (RPF) as well as multiparametric kidney MRI. Magnetic resonance imaging of the kidneys will be performed prior to each biopsy to correlate the molecular and structural damage seen at kidney biopsy with the level of perfusion, oxygen availability and fibrosis detected by imaging. Imaging of the kidneys will be done as near to the time of each kidney biopsy as possible. Participants will be followed annually after completion of the mechanistic clinical trial until death or development of end-stage kidney disease.
Participants will be followed for potential adverse events for an additional two months post six-month biopsy.
- Conditions
- Type 2 Diabetes, Diabetic Kidney Disease
- Being tested
- SGLT2 inhibitor
- Keywords
- Kidney biopsy, Kidney MRI, SGLT2 inhibitor, SGLT2i, FDA-approved, Renal biopsy, Renal MRI, Type 2 diabetes, Canagliflozin, INVOKANA
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGLT2 inhibitorDrug
Also called Canagliflozin, Invokana
All participants will be receive 100 mg/daily doses of Canagliflozin (INVOKANA) for 6 months. Canagliflozin is a Sodium-glucose cotransporter 2 (SGLT2) inhibitor
| Study group | Role | What they receive |
|---|---|---|
| SGLT2i Arm | Other | Not described Receives: Drug: SGLT2 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular basement membrane (GBM) width and mesangial expansion
Measured by morphometric examination of kidney tissue
Measured: Baseline and 6 months
Secondary outcomes (1)
Kidney Transcript Changes
Molecular changes measured by change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens
Measured: 6 month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2024
- Study start1 Jan 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open-label, non-randomized mechanistic trial of an FDA-approved drug
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Denver
- Responsible party
- Principal investigator, Markus Bitzer, University of Michigan
- Investigators
- Markus Bitzer, MD, Principal investigator, Professor of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06291155
- Sponsor's protocol ID
- HUM00222335
- Status last verified
- Jun 2026
- First submitted
- 26 Feb 2024
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Mechanisms of SGLT2 Inhibition in Diabetic Kidney Disease
- ClinicalTrials.gov ID
- NCT06291155
- Acronym / sponsor ID
- HUM00222335
- Conditions
- Type 2 Diabetes, Diabetic Kidney Disease
- Keywords
- Kidney biopsy, Kidney MRI, SGLT2 inhibitor, SGLT2i, FDA-approved, Renal biopsy, Renal MRI, Type 2 diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- University of Colorado, Denver
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 4 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The purpose of this protocol is to examine the effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin on intrarenal transcripts of energy metabolism in adults with type 2 diabetes and early diabetic kidney disease (DKD) via 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. The primary objective of this study is to determine whether canagliflozin affects intrarenal transcripts of energy metabolism in adults with type 2 diabetes and early DKD.
The primary outcomes measure will be change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens obtained at study entry and after 6 months of study drug. Secondary outcomes include assessing the effects of canagliflozin on structural progression of DKD assessed by morphometric examination of kidney tissue specimens from the paired research biopsies. Additional secondary outcomes include measures of glomerular filtration rate (GFR) and renal plasma flow (RPF) as well as multiparametric kidney MRI. Magnetic resonance imaging of the kidneys will be performed prior to each biopsy to correlate the molecular and structural damage seen at kidney biopsy with the level of perfusion, oxygen availability and fibrosis detected by imaging. Imaging of the kidneys will be done as near to the time of each kidney biopsy as possible. Participants will be followed annually after completion of the mechanistic clinical trial until death or development of end-stage kidney disease.
Participants will be followed for potential adverse events for an additional two months post six-month biopsy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open-label, non-randomized mechanistic trial of an FDA-approved drug
| Arm | Type | Receives |
|---|---|---|
| SGLT2i Arm | Other | Drug: SGLT2 inhibitor |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 18-80 years.
- 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.
Key exclusion criteria (28 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SGLT2 inhibitorAlso: Canagliflozin, InvokanaAll participants will be receive 100 mg/daily doses of Canagliflozin (INVOKANA) for 6 months. Canagliflozin is a Sodium-glucose cotransporter 2 (SGLT2) inhibitor | Drug | SGLT2i Arm |
Primary outcome
Glomerular basement membrane (GBM) width and mesangial expansion
Time frame: Baseline and 6 months
Measured by morphometric examination of kidney tissue
1 secondary outcome
Kidney Transcript Changes
Time frame: 6 month follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Markus Bitzer, MD principal investigator
Professor of Internal Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing SGLT2 inhibitor in people with Type 2 Diabetes and Diabetic Kidney Disease, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chrysta C Lienczewski, BS (734-615-5021, boridley@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glomerular basement membrane (GBM) width and mesangial expansion (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.