Evidence map›Paper›PMID 38707807›Full record

ArticleKidney international reports2024

Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Gabriel C Barsotti, Randy Luciano, Ashwani Kumar, Kristin Meliambro, Vijayakumar Kakade, Joji Tokita, Abhijit Naik, Jia Fu, Elizabeth Peck, John Pell and 12 more

Abstract read
In one paragraph

Article in Kidney international reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Gabriel C BarsottiSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Randy LucianoSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Ashwani KumarSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Kristin MeliambroDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Vijayakumar KakadeSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Joji TokitaDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abhijit NaikDivision of Nephrology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Jia FuDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Elizabeth PeckClinical Research Coordinator, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
John PellSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Anand ReghuvaranSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
E M TanvirSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Prashant PatelInvestigational Drug Service, Department of Pharmacy Services, Yale New Haven Hospital, Connecticut, USA.
Weijia ZhangDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Fan LiDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
Gilbert MoeckelDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
Sudhir PerincheriDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
Lloyd CantleySection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Dennis G MoledinaSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
F Perry WilsonSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
John C HeDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Madhav C MenonSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Biomarkers for acute interstitial nephritis in humansR01DK128087 · NIDDK · YALE UNIVERSITY · PI MOLEDINA, DENNIS G. · 2021 to 2025
$2.9M
Dichotomous roles of Shroom3 in Tubular cells and Podocytes in native and allograft kidneysR01DK122164 · NIDDK · YALE UNIVERSITY · PI Madhav C Menon · 2019 to 2026
$2.7M
Role of AMP-kinase pathway in the regulation of Minimal change disease-to-FSGS transitionR01DK132274 · NIDDK · YALE UNIVERSITY · PI Madhav C Menon · 2023 to 2026
$2.1M
Identification of Non-Invasive Biomarkers and Indices for Diagnosis of Drug-Induced Acute Interstitial NephritisK23DK117065 · NIDDK · YALE UNIVERSITY · PI MOLEDINA, DENNIS G. · 2018 to 2022
$920k
Modelling mechanisms of progressive chronic kidney disease in APOL1 high-risk live-donors using BAC-Transgenic miceR21AI178705 · NIAID · YALE UNIVERSITY · PI ISHIBE, SHUTA, MENON, MADHAV C · 2023 to 2024
$461k
NCATS NIH HHS UL1 TR001863NIAID NIH HHS R21 AI178705NIDDK NIH HHS K23 DK117065NIDDK NIH HHS R01 DK122164NIDDK NIH HHS R01 DK128087NIDDK NIH HHS R01 DK132274
6 · The paper itself

Abstract

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes. Conversely, in FSGS, AMPK-activation using metformin (MF) mitigated podocytopenia and azotemia. Observational studies also support beneficial effects of MF on proteinuria and chronic kidney disease (CKD) outcomes in diabetes. A randomized controlled trial (RCT) to test MF in podocyte injury with FSGS has not yet been conducted. Methods: We report the rationale and design of phase 2, double-blind, placebo-controlled RCT evaluating the efficacy and safety of MF as adjunctive therapy in FSGS. By randomizing 30 patients with biopsy-confirmed FSGS to MF or placebo (along with standard immunosuppression), we will study mechanistic biomarkers that correlate with podocyte injury or depletion and evaluate outcomes after 6 months. We specifically integrate novel urine, blood, and tissue markers as surrogates for FSGS progression along with unbiased profiling strategies. Results and Conclusion: Our phase 2 trial will provide insight into the potential efficacy and safety of MF as adjunctive therapy in FSGS-a crucial step to developing a larger phase 3 study. The mechanistic assays here will guide the design of other FSGS trials and contribute to understanding AMPK activation as a potential therapeutic target in FSGS. By repurposing an inexpensive agent, our results will have implications for FSGS treatment in resource-poor settings.

Indexed as

adjunctive therapyAMP-activated protein kinasefocal segmental glomerulosclerosismetforminphase 2randomized trial

Identifiers

PMID38707807
PMCPMC11068976

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.