Type 2 DiabetesPhase 2NCT05507892
Renal Mechanism of SGLT2 Inhibition
A Phase 2 study testing canagliflozin and Aminohippurate Sodium Inj 20% in people with Type 2 Diabetes and Diabetic Kidney Disease, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
Canagliflozin is an oral drug which is currently approved for use in patients with type 2 diabetes by the US Food and Drug Administration (FDA). Canagliflozin acts by increasing salt and sugar loss in the urine, and has shown to protect heart, kidney, and blood vessel function in patients with 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?
- canagliflozin and Aminohippurate Sodium Inj 20%
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Oct 2022to 15 Dec 2026
- Phase
- Phase 2
- 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.
- 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.
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 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.
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- 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.
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Molecular Mechanisms of SGLT2 Inhibition in Diabetic Kidney Disease
Canagliflozin is an oral drug which is currently approved for use in patients with type 2 diabetes by the US Food and Drug Administration (FDA). Canagliflozin acts by increasing salt and sugar loss in the urine, and has shown to protect heart, kidney, and blood vessel function in patients with type 2 diabetes. However, it is unknown how canagliflozin protects the kidneys from disease. Therefore, this study plans to learn more about how canagliflozin works to protect against diabetic kidney disease in adults with type 2 diabetes. This study will use state-of-the-art kidney imaging, kidney biopsies and detailed testing of kidney function to determine the mechanisms of protection afforded by canagliflozin.
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.
Of note, participants will be offered the option of staying on the SGLT2 inhibitor free of charge until 18 months after the last study biopsy or 24 months after enrollment to obtain the long-term impact of SGLT2 on GFR and proteinuria.
- Conditions
- Type 2 Diabetes, Diabetic Kidney Disease
- Being tested
- canagliflozin, Aminohippurate Sodium Inj 20%
- 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.
canagliflozinDrug
Also called Invokana
Canagliflozin is in a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It is a used to treat type 2 diabetes. Canagliflozin lowers blood sugars by causing the kidneys to excrete more glucose in the urine.
Aminohippurate Sodium Inj 20%Drug
Also called -Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL -Para-aminohippurate
Diagnostic aid/agent used to measure renal plasma flow (RPF) PAH (Basic Pharma, Geleen, Netherlands) has been used to measure RPF in human research for 7 decades, and is very well tolerated and generally recognized as safe with low toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants who will receive 100 mg of canagliflozin daily for six (6) months in addition to standard of care. Receives: Drug: canagliflozin; Drug: Aminohippurate Sodium Inj 20% |
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: 6 months
Kidney Transcript Changes
Molecular changes measured by change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens
Measured: 6 months
Secondary outcomes (5)
Cortical R2
Measured by Blood Oxygen Level Dependent (BOLD) MRI; Participants will be scanned in a supine position with a 3T MRI scanner. Spine array and body array receiver coils will be used to maximize image uniformity. Following initial localizer scans, coronal Sec T2-weighted MR images will be obtained to delineate cortical kidney regions. The image acquisition will be respiratory-gated to ensure accurate image co-registration with the respiratory-gated diffusion acquisitions.
Measured: 6 months
Medullary R2
Measured by Blood Oxygen Level Dependent (BOLD) MRI; Participants will be scanned in a supine position with a 3T MRI scanner. Spine array and body array receiver coils will be used to maximize image uniformity. Following initial localizer scans, coronal Sec T2-weighted MR images will be obtained to delineate medullary kidney regions. The image acquisition will be respiratory-gated to ensure accurate image co-registration with the respiratory-gated diffusion acquisitions.
Measured: 6 months
Renal Perfusion
Measured by Arterial Spin Labeling (ASL)
Measured: 6 months
Glomerular Filtration Rate (GFR)
Measured by iohexol clearance; An intravenous (IV) line will be placed, and participants will be asked to empty their bladders. Spot plasma and urine samples will be collected prior to iohexol infusion. Iohexol will be administered through bolus IV injection (36 mg/kg/dose), followed by infusion (15mg/min over 180 min.) An equilibration period of 120 min was used and blood collections for iohexol plasma disappearance were drawn at +120, +150, +180 min.
Measured: 3 Hours
Renal Plasma Flow (RPF)
Measured by para-aminohippurate (PAH) clearance; An intravenous (IV) line will be placed, and participants will be asked to empty their bladders. Spot plasma and urine samples will be collected prior to PAH infusion. PAH (2 g/10 mL, prepared by Basic Pharma, with a dose of (16 mg/kg or 12 mg/kg depending on eGFR) will be given slowly over 5 min followed by a continuous infusion of 8 mL of PAH and 42 mL of normal saline at a rate or 7.2 mg/kg/ hr or 5.0 mg/kg/hr for 2 h, depending on eGFR. After an equilibration period, blood will be drawn at 90, 120, and 150 min, and RPF will be calculated as PAH clearance divided by the estimated extraction ratio of PAH, which varies by the level of GFR.
Measured: 2.5 Hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2022
- Study start10 Oct 2022
- Primary completion15 Dec 2026 (estimated)
- Study completion15 Dec 2026 (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 Colorado, DenverThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is 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.
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05507892
- Sponsor's protocol ID
- 22-0668
- Status last verified
- May 2026
- First submitted
- 17 Aug 2022
- Last updated
- 2 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 2 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
- NCT05507892
- Acronym / sponsor ID
- 22-0668
- Conditions
- Type 2 Diabetes, Diabetic Kidney Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Michigan
- Study start
- 10 Oct 2022 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 19 Aug 2022 (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.
Canagliflozin is an oral drug which is currently approved for use in patients with type 2 diabetes by the US Food and Drug Administration (FDA). Canagliflozin acts by increasing salt and sugar loss in the urine, and has shown to protect heart, kidney, and blood vessel function in patients with type 2 diabetes. However, it is unknown how canagliflozin protects the kidneys from disease. Therefore, this study plans to learn more about how canagliflozin works to protect against diabetic kidney disease in adults with type 2 diabetes. This study will use state-of-the-art kidney imaging, kidney biopsies and detailed testing of kidney function to determine the mechanisms of protection afforded by canagliflozin.
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.
Of note, participants will be offered the option of staying on the SGLT2 inhibitor free of charge until 18 months after the last study biopsy or 24 months after enrollment to obtain the long-term impact of SGLT2 on GFR and proteinuria.
Study design
- Primary purpose
- Treatment
- 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. This trial will enroll 40 participants who will receive 100 mg of canagliflozin daily for six (6) months in addition to standard of care.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: canagliflozin, Drug: Aminohippurate Sodium Inj 20%Participants who will receive 100 mg of canagliflozin daily for six (6) months in addition to standard of care. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 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 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.
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 |
|---|---|---|
| canagliflozinAlso: InvokanaCanagliflozin is in a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It is a used to treat type 2 diabetes. Canagliflozin lowers blood sugars by causing the kidneys to excrete more glucose in the urine. | Drug | Treatment |
| Aminohippurate Sodium Inj 20%Also: -Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL -Para-aminohippurateDiagnostic aid/agent used to measure renal plasma flow (RPF) PAH (Basic Pharma, Geleen, Netherlands) has been used to measure RPF in human research for 7 decades, and is very well tolerated and generally recognized as safe with low toxicity. | Drug | Treatment |
Primary outcome
Glomerular basement membrane (GBM) width and mesangial expansion
Time frame: 6 months
measured by morphometric examination of kidney tissue
Kidney Transcript Changes
Time frame: 6 months
Molecular changes measured by change in transcripts as assessed by single-cell RNA sequencing of kidney biopsy specimens
5 secondary outcomes
Cortical R2
Time frame: 6 months
Medullary R2
Time frame: 6 months
Renal Perfusion
Time frame: 6 months
Glomerular Filtration Rate (GFR)
Time frame: 3 Hours
Renal Plasma Flow (RPF)
Time frame: 2.5 Hours
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 2 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing canagliflozin and Aminohippurate Sodium Inj 20% in people with Type 2 Diabetes and Diabetic Kidney Disease, run by University of Colorado, Denver at 2 sites 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 7 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 2 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 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glomerular basement membrane (GBM) width and mesangial expansion (time frame: 6 months). The study lists 2 primary outcomes in all. 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 2 Jun 2026.