Focal Segmental GlomerulosclerosisPhase 1/2AMP-FSGSNCT06090227
AMPK-activation by Metformin in FSGS: AMP-FSGS
A Phase 1/2 study of Focal Segmental Glomerulosclerosis, run by Yale University at 2 sites in United States.
Trial summary
The primary objective of this study is to determine whether extended-release MF (in addition to standard of care (S-o-C)) is superior to placebo in reducing podocyte injury and promoting podocyte survival by 6-months in Focal Segmental Glomerulosclerosis (FSGS). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Focal Segmental Glomerulosclerosis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Dec 2023to Nov 2027
- Phase
- Phase 1/2
- 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
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged greater than or equal to 18 years, but </= 80 years age at the time of signing the informed consent
- Biopsy-confirmed primary FSGS as defined by expert renal pathology at either institutions. For homogeneity of diagnoses, demonstrable segmental or global sclerosis lesions (>/=1 glomerulus) with diffuse podocyte foot process effacement by electron microscopy (>/+ 50% of examined glomerular tufts), or show evidence of mesangial expansion or mesangial sclerosis, also confirmed by electron microscopy.
- Therapeutic plan by treating physician for immunomodulatory treatment using Glucocorticoids.
- Ability to take oral medication and be willing to adhere to the MF or Placebo regimen
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of VPA administration. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
Who cannot join
- Liver disease: confirmed cirrhosis liver (any stage), acute hepatitis (> 2 fold increase in liver enzymes, any coagulopathy, hyperbilirubinemia, ascites or encephalopathy)
- estimated GFR < 32 ml/min
- Diabetes Mellitus diagnosis at the time of biopsy or need for oral hypoglycemic agents/Insulin, or taking Metformin for other indications
- Treatment with another investigational drug or other intervention within 3 months
- Current pregnancy or desire to become pregnant during the study period
- Unwilling to use two forms of birth control (for women of childbearing age)
Show all 18Show fewer
- Under hospice care
- Confirmed Dementia diagnoses in EMR problem list
- Incarceration
- Homelessness
- Inability to consent
- Currently enrolled in (or completed within the past 30 days) a study of an investigational drug or device.
- Life expectancy of less than 6 months as determined by the clinical judgement of the patient's primary physician
- Allergy or sensitivity to Metformin
- Platelet count < 100,000/µL; INR > 1.5; Bleeding diathesis or blood thinner use contraindicating biopsy.
- Bleeding diathesis or blood thinner use contraindicating biopsy will be excluded entirely from participation in research biopsy portion of study only, even if anticoagulation/blood thinners can be held temporarily.
- Simultaneous use of Carbonic anhydrase inhibitor agents
- Use of systemic immunosuppressive medication for non-renal indications
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06510
Madhav Menon, madhav.menon@yale.edu
Francis P Wilson, MD
- Recruiting
Mount Sinai Hospital
New York, New York, 10029
Cijiang He, cijiang.he@mssm.edu
Joji Tokita
About this study
The primary objective of this study is to determine whether extended-release MF (in addition to standard of care (S-o-C)) is superior to placebo in reducing podocyte injury and promoting podocyte survival by 6-months in Focal Segmental Glomerulosclerosis (FSGS).
Read the detailed description
Focal Segmental glomerulosclerosis (FSGS) is currently the most common primary glomerular disease that progresses to ESKD in the US. FSGS is typified by significant proteinuria, and by disorganization of the actin cytoskeleton of highly specialized epithelial cells which support the glomerular capillary loop called podocytes. Podocytes are characterized by foot processes, whose disorganization with injury is visualized on electron microscopy as foot process effacement (FPE). Podocytes are also incapable of self-renewal, and podocyte loss over ~40% per glomerulus leads to proteinuria, the nephrotic syndrome (NS) and FSGS. Such critical podocyte loss alone is sufficient for progressive CKD and ESKD. Currently, the reported rate of complete and/or partial response is 40-70% in various series with a rate of progression to ESKD 30-53% in 5-10 years.
Distinct from FSGS, Minimal Change Disease (MCD), which despite showing similar diffuse FPE and NS, has preserved podocyte numbers and rare progression to ESKD (5-20% in 20 years). MCD can be morphologically indistinguishable from early FSGS, and some MCD cases reportedly transition to FSGS. Hence, identifying and targeting mechanisms in MCD that specifically promote survival of injured podocytes with FPE, could help switch an FSGS phenotype to an "MCD-like" phenotype, and prevent or retard progression of FSGS. Currently, therapeutics in FSGS focus on immune modulation, or on hemodynamic interventions used in generically all cases of NS. Specific strategies to directly promote podocyte survival and limit podocytopenia to within the critical threshold during injury, have not been pursued clinically. Hence, many FSGS cases will progress to ESKD or encounter dose limiting side-effects of immune therapies (corticosteroids, or other agents), representing a significant therapeutic gap in the field.
In this context, MF is an Ampk-activator that is widely used, demonstrably safe, and inexpensive with reported renal benefit in diabetic and non-diabetic CKD. Its specific utility to promote cell survival of injured podocytes in FSGS has never been tested. Our preclinical data shows that an "MCD-like" pathology with podocyte injury/FPE transitioned to podocytopenia and FSGS by AMPK inhibition, while AMPK activation with MF mitigated podocytopenia in FSGS models.
The purpose of this study is to test whether Metformin use in individuals with FSGS as an adjunct to standard -of-care (corticosteroids, anti RAAS measures, BP control) is safe and will activate kidney cell AMPK and reduce podocyte injury. The primary objective is to determine whether extended-release MF (in addition to standard of care (S-o-C)) is superior to placebo in reducing podocyte injury and promoting podocyte survival by 6-months in Focal Segmental Glomerulosclerosis (FSGS). Specifically, for this purpose, this study will primarily evaluate sequential urinary podocyte mRNA excretion to identify individual urinary mRNA trajectories representing podocyte injury/depletion and potential prognostic signals in the MF study limb vs control.
A secondary objective of this study is to use multiple blood, urine and biopsy assays to test whether the addition of Metformin ( to S-o-C) mitigates kidney disease progression parameters superior to placebo. These assays will include large scale urine and serum protein profiling, protein and RNA tests performed in kidney biopsies.
Another secondary objective of this study is to test whether the addition of Metformin ( to S-o-C) is safe in patients with proteinuria and FSGS. This will be accomplished by specific questionnaires and blood tests geared towards MF-associated adverse effects.
Results of this study will inform a larger, phase 2/3 randomized trial which will evaluate the efficacy of MF treatment versus placebo in attenuating proteinuria and kidney function decline in FSGS.
- Conditions
- Focal Segmental Glomerulosclerosis
- Being tested
- Metformin + Standard of Care, Placebo + Standard of Care
- Medical subject headings
- Glomerulosclerosis, Focal Segmental
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin + Standard of CareDrug
Administration of daily oral extended-release Metformin 500 mg tablets with standard of care for 6 months.
Placebo + Standard of CareOther
Administration of daily placebo tablets with standard of care for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Metformin + Standard of Care | Experimental | Administration of daily oral extended-release Metformin 500 mg tablets with standard of care for 6 months. Receives: Drug: Metformin + Standard of Care |
| Placebo + Standard of Care | Placebo comparator | Administration of daily placebo tablets with standard of care for 6 months. Receives: Other: Placebo + Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Slope of urinary NPHS2:Creatinine ratio
Measure of podocinuria via evaluation of urine podocin mRNA(nphs2) (measured as number of molecules detected by qPCR in the collected urine pellet) over the creatinine concentration. Intended for evaluation of efficacy of metformin versus placebo.
Measured: 6 months following randomization
Secondary outcomes (28)
estimated Glomerular Filtration Rate (eGFR)
Calculated from serum creatinine (mg/dl) using the CKD-EPI formula. Intended for evaluation of efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Slope of eGFR
Change in eGFR from randomization to 6 months by incorporating eGFR at all timepoints in study between baseline and 6 months post-randomization. eGFR calculated from serum creatinine (mg/dl) using the CKD-EPI formula. Intended for evaluation of efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Urine protein:creatinine ratio
Calculated ratio of urine protein and creatinine, each collected from the electronic medical record. Intended for evaluation of clinical efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Slope of urine protein:creatinine ratio
Change in urine protein:creatinine ratio from randomization to 6 months by incorporating urine protein:creatinine ratio at all timepoints in study between baseline and 6 months post-randomization. Intended for evaluation of clinical efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Complete remission
Calculated as the number of patients in complete remission, defined as <0.5 gm urine protein excretion over 24 hours, or urine protein creatinine ratio < 0.5 at 6 months post-randomization. Intended for evaluation of clinical efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Complete or partial remission
Calculated as the number of patients with complete remission (defined as <0.5 gm urine protein excretion over 24 hours, or urine protein creatinine ratio < 0.5) or partial remission (>50% reduction in proteinuria from pre-randomization). Intended for evaluation of clinical efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Discontinuation of study drug
Number of patients who discontinued study drug for any reason within 6 months of randomization. Intended for evaluation of patient compliance of metformin use.
Measured: Within 6 months post-randomization
Modified Kidney Disease Quality of Life (KDQOL) score
Calculated as the mean (standard deviation) of all total scores. Total scores are calculated by combining scores of 8 subsections of the KDQOL, and range from 0 - 163, with higher scores representing better quality of life. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: 1 month post-randomization
Modified Kidney Disease Quality of Life (KDQOL) score
Calculated as the mean (standard deviation) of all total scores. Total scores are calculated by combining scores of 8 subsections of the KDQOL, and range from 0 - 163, with higher scores representing better quality of life. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: 6 months post-randomization
Hypoglycemia symptom scores
Calculated as the mean (standard deviation) of all total scores. Total scores are calculated by combining scores of 6 subsections of the questionnaire, and range from 0 - 18, with higher scores representing greater symptoms. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: 6 months post-randomization
Gastrointenstinal symptom scores
Calculated as the mean (standard deviation) of all total scores. Total scores are calculated by combining scores of 15 subsections of the questionnaire, and range from 0 - 105, with higher scores representing greater symptoms. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: 1 month post-randomization
Gastrointenstinal symptom scores
Calculated as the mean (standard deviation) of all total scores. Total scores are calculated by combining scores of 15 subsections of the questionnaire, and range from 0 - 105, with higher scores representing greater symptoms. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: 6 months post-randomization
Kidney biopsy fibrosis scores
Evaluation of kidney fibrosis as measured by quantification of Masson's Trichrome staining under microscopy of biopsy at 6 months post-randomization. Scores will be grouped by the following: <10%, 10-25%, 25-50%, > 50%. Intended for evaluation of clinical efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Number of patients with Lactate levels>2.5
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Lactate levels>5
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Vitamin B12 levels <lower limit of Normal
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with serum glutamic-oxaloacetic transaminase (SGOT) >2 fold increase
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Serum Glutamic Pyruvic Transaminase (SGPT) >2 fold increase
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Serum amyloid P component (SAP) >2 fold increase
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Bililirubin-Total >2
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Bilirubin indirect >1
As determined from the electronic medical record. Intended for evaluation of adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with hemoglobin (Hb) <9
As determined from the electronic medical record. Intended for evaluation of disease progression and adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with hematocrit (Hct) <27
As determined from the electronic medical record. Intended for evaluation of disease progression and adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with mean corpuscular volume (MCV) >100
As determined from the electronic medical record. Intended for evaluation of disease progression and adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Number of patients with Total White Blood Cells (WBC) <1500
As determined from the electronic medical record. Intended for evaluation of disease progression and adverse effects of metformin versus placebo.
Measured: Within 6 months post-randomization
Slope of Urine Nphs2
Change in urine podocin mRNA(Nphs2), measured as number of molecules detected by qPCR in the collected urine pellet over the creatinine concentration. Slope measured by incorporating nphs2 measurements at all timepoints in study between baseline and 6 months post-randomization. Intended for evaluation of efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Slope of Urine Aqp2
Change in urine Aquaporin-2 mRNA(Aqp2), measured as number of molecules detected by qPCR in the collected urine pellet over the creatinine concentration. Slope measured by incorporating Aqp2 measurements at all timepoints in study between baseline and 6 months post-randomization. Intended for evaluation of efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Slope of Urine Tgfb1
Change in urine transforming growth factor-beta1 mRNA (Tgfb1), measured as number of molecules detected by qPCR in the collected urine pellet over the creatinine concentration. Slope measured by incorporating Tgfb1 measurements at all timepoints in study between baseline and 6 months post-randomization. Intended for evaluation of efficacy of metformin versus placebo.
Measured: 6 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2023
- Study start14 Dec 2023
- Primary completionNov 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal Segmental GlomerulosclerosisStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Madhav Menon, MD, Principal investigator, Yale UniversityCijiang He, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06090227
- Sponsor's protocol ID
- 2000035723
- Other IDs
- HT9425-23-1-0454
- Acronym
- AMP-FSGS
- Status last verified
- Jan 2026
- First submitted
- 13 Oct 2023
- Last updated
- 3 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 3 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AMPK-activation by Metformin in FSGS: AMP-FSGS
- ClinicalTrials.gov ID
- NCT06090227
- Acronym / sponsor ID
- AMP-FSGS / 2000035723
- Conditions
- Focal Segmental Glomerulosclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 14 Dec 2023 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 19 Oct 2023 (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 primary objective of this study is to determine whether extended-release MF (in addition to standard of care (S-o-C)) is superior to placebo in reducing podocyte injury and promoting podocyte survival by 6-months in Focal Segmental Glomerulosclerosis (FSGS).
Detailed description
Focal Segmental glomerulosclerosis (FSGS) is currently the most common primary glomerular disease that progresses to ESKD in the US. FSGS is typified by significant proteinuria, and by disorganization of the actin cytoskeleton of highly specialized epithelial cells which support the glomerular capillary loop called podocytes. Podocytes are characterized by foot processes, whose disorganization with injury is visualized on electron microscopy as foot process effacement (FPE). Podocytes are also incapable of self-renewal, and podocyte loss over ~40% per glomerulus leads to proteinuria, the nephrotic syndrome (NS) and FSGS. Such critical podocyte loss alone is sufficient for progressive CKD and ESKD. Currently, the reported rate of complete and/or partial response is 40-70% in various series with a rate of progression to ESKD 30-53% in 5-10 years.
Distinct from FSGS, Minimal Change Disease (MCD), which despite showing similar diffuse FPE and NS, has preserved podocyte numbers and rare progression to ESKD (5-20% in 20 years). MCD can be morphologically indistinguishable from early FSGS, and some MCD cases reportedly transition to FSGS. Hence, identifying and targeting mechanisms in MCD that specifically promote survival of injured podocytes with FPE, could help switch an FSGS phenotype to an "MCD-like" phenotype, and prevent or retard progression of FSGS. Currently, therapeutics in FSGS focus on immune modulation, or on hemodynamic interventions used in generically all cases of NS. Specific strategies to directly promote podocyte survival and limit podocytopenia to within the critical threshold during injury, have not been pursued clinically. Hence, many FSGS cases will progress to ESKD or encounter dose limiting side-effects of immune therapies (corticosteroids, or other agents), representing a significant therapeutic gap in the field.
In this context, MF is an Ampk-activator that is widely used, demonstrably safe, and inexpensive with reported renal benefit in diabetic and non-diabetic CKD. Its specific utility to promote cell survival of injured podocytes in FSGS has never been tested. Our preclinical data shows that an "MCD-like" pathology with podocyte injury/FPE transitioned to podocytopenia and FSGS by AMPK inhibition, while AMPK activation with MF mitigated podocytopenia in FSGS models.
The purpose of this study is to test whether Metformin use in individuals with FSGS as an adjunct to standard -of-care (corticosteroids, anti RAAS measures, BP control) is safe and will activate kidney cell AMPK and reduce podocyte injury. The primary objective is to determine whether extended-release MF (in addition to standard of care (S-o-C)) is superior to placebo in reducing podocyte injury and promoting podocyte survival by 6-months in Focal Segmental Glomerulosclerosis (FSGS). Specifically, for this purpose, this study will primarily evaluate sequential urinary podocyte mRNA excretion to identify individual urinary mRNA trajectories representing podocyte injury/depletion and potential prognostic signals in the MF study limb vs control.
A secondary objective of this study is to use multiple blood, urine and biopsy assays to test whether the addition of Metformin ( to S-o-C) mitigates kidney disease progression parameters superior to placebo. These assays will include large scale urine and serum protein profiling, protein and RNA tests performed in kidney biopsies.
Another secondary objective of this study is to test whether the addition of Metformin ( to S-o-C) is safe in patients with proteinuria and FSGS. This will be accomplished by specific questionnaires and blood tests geared towards MF-associated adverse effects.
Results of this study will inform a larger, phase 2/3 randomized trial which will evaluate the efficacy of MF treatment versus placebo in attenuating proteinuria and kidney function decline in FSGS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin + Standard of Care | Experimental | Drug: Metformin + Standard of CareAdministration of daily oral extended-release Metformin 500 mg tablets with standard of care for 6 months. |
| Placebo + Standard of Care | Placebo comparator | Other: Placebo + Standard of CareAdministration of daily placebo tablets with standard of care for 6 months. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged greater than or equal to 18 years, but </= 80 years age at the time of signing the informed consent
- Biopsy-confirmed primary FSGS as defined by expert renal pathology at either institutions. For homogeneity of diagnoses, demonstrable segmental or global sclerosis lesions (>/=1 glomerulus) with diffuse podocyte foot process effacement by electron microscopy (>/+ 50% of examined glomerular tufts), or show evidence of mesangial expansion or mesangial sclerosis, also confirmed by electron microscopy.
- Therapeutic plan by treating physician for immunomodulatory treatment using Glucocorticoids.
Key exclusion criteria (18 listed)
- Liver disease: confirmed cirrhosis liver (any stage), acute hepatitis (> 2 fold increase in liver enzymes, any coagulopathy, hyperbilirubinemia, ascites or encephalopathy)
- estimated GFR < 32 ml/min
- Diabetes Mellitus diagnosis at the time of biopsy or need for oral hypoglycemic agents/Insulin, or taking Metformin for other indications
- Treatment with another investigational drug or other intervention within 3 months
- Current pregnancy or desire to become pregnant during the study period
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 |
|---|---|---|
| Metformin + Standard of CareAdministration of daily oral extended-release Metformin 500 mg tablets with standard of care for 6 months. | Drug | Metformin + Standard of Care |
| Placebo + Standard of CareAdministration of daily placebo tablets with standard of care for 6 months. | Other | Placebo + Standard of Care |
Primary outcome
Slope of urinary NPHS2:Creatinine ratio
Time frame: 6 months following randomization
Measure of podocinuria via evaluation of urine podocin mRNA(nphs2) (measured as number of molecules detected by qPCR in the collected urine pellet) over the creatinine concentration. Intended for evaluation of efficacy of metformin versus placebo.
28 secondary outcomes
estimated Glomerular Filtration Rate (eGFR)
Time frame: 6 months post-randomization
Slope of eGFR
Time frame: 6 months post-randomization
Urine protein:creatinine ratio
Time frame: 6 months post-randomization
Slope of urine protein:creatinine ratio
Time frame: 6 months post-randomization
Complete remission
Time frame: 6 months post-randomization
Complete or partial remission
Time frame: 6 months post-randomization
Discontinuation of study drug
Time frame: Within 6 months post-randomization
Modified Kidney Disease Quality of Life (KDQOL) score
Time frame: 1 month post-randomization
Modified Kidney Disease Quality of Life (KDQOL) score
Time frame: 6 months post-randomization
Hypoglycemia symptom scores
Time frame: 6 months post-randomization
Gastrointenstinal symptom scores
Time frame: 1 month post-randomization
Gastrointenstinal symptom scores
Time frame: 6 months post-randomization
Kidney biopsy fibrosis scores
Time frame: 6 months post-randomization
Number of patients with Lactate levels>2.5
Time frame: Within 6 months post-randomization
Number of patients with Lactate levels>5
Time frame: Within 6 months post-randomization
Number of patients with Vitamin B12 levels <lower limit of Normal
Time frame: Within 6 months post-randomization
Number of patients with serum glutamic-oxaloacetic transaminase (SGOT) >2 fold increase
Time frame: Within 6 months post-randomization
Number of patients with Serum Glutamic Pyruvic Transaminase (SGPT) >2 fold increase
Time frame: Within 6 months post-randomization
Number of patients with Serum amyloid P component (SAP) >2 fold increase
Time frame: Within 6 months post-randomization
Number of patients with Bililirubin-Total >2
Time frame: Within 6 months post-randomization
Number of patients with Bilirubin indirect >1
Time frame: Within 6 months post-randomization
Number of patients with hemoglobin (Hb) <9
Time frame: Within 6 months post-randomization
Number of patients with hematocrit (Hct) <27
Time frame: Within 6 months post-randomization
Number of patients with mean corpuscular volume (MCV) >100
Time frame: Within 6 months post-randomization
Number of patients with Total White Blood Cells (WBC) <1500
Time frame: Within 6 months post-randomization
Slope of Urine Nphs2
Time frame: 6 months post-randomization
Slope of Urine Aqp2
Time frame: 6 months post-randomization
Slope of Urine Tgfb1
Time frame: 6 months post-randomization
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 3 Feb 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.
Madhav Menon, MD principal investigator
Yale University
Cijiang He principal investigator
Icahn School of Medicine at Mount Sinai
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study of Focal Segmental Glomerulosclerosis, run by Yale University 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 18 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 3 Feb 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Madhav C Menon, MD (20373734507, madhav.menon@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Slope of urinary NPHS2:Creatinine ratio (time frame: 6 months following randomization). 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 3 Feb 2026.