Protocol for the FibroCAN study: a randomised controlled trial of finerenone treatment for early-stage cardiovascular autonomic neuropathy in type 2 diabetes.

Abstract

Introduction: Cardiovascular autonomic neuropathy (CAN) is a serious, untreatable complication of diabetes that contributes to excess cardiovascular mortality and morbidity. CAN is associated with increased fibrosis and inflammation, possibly driven by increased sympathetic activity and overactive mineralocorticoid receptors (MRs). These may represent a potential therapeutic target. MR antagonists (MRAs) improve autonomic function in non-diabetic diseases, and finerenone, a non-steroidal MRA, has demonstrated promising results in managing diabetic kidney disease and cardiovascular complications, suggesting its potential as a novel therapy for early-stage CAN. This trial aims to evaluate whether daily administration of finerenone can modify the disease progression of early-stage CAN.

Methods and analysis: This trial is a two-centre, double-blind, parallel-group, 1:1 randomised, placebo-controlled study evaluating the effect of 78 weeks of intervention with finerenone or placebo on early-stage CAN in 100 individuals with type 2 diabetes in Denmark. The primary endpoint is the between-group difference in the expiration:inspiration ratio of the cardiovascular autonomic reflex tests (CARTs). Secondary endpoints are the between-group differences in the remaining CARTs, heart rate variability measures and fibrosis markers. Treatment effects on other forms of neuropathy and related pathological mechanisms will be explored.

Ethics and dissemination: The study complies with the Declaration of Helsinki and the International Counsil for Harmonisation good clinical practice guidelines, with ethics approval obtained from the Danish Medical Research Ethics Committee. All participants will provide written informed consent. Due to the risk of hyperkalaemia associated with finerenone, safety will be closely monitored throughout the study. Findings will be disseminated through peer-reviewed publications, conference presentations and clinical trial registries. A lay summary will be provided to participants on study completion.

Trial registration number: ClinicalTrials.gov: NCT06906081; registration date: 25 March 2025. Clinical Trials Information System: EUCT no. 2024-516597-30-00; registration date: 3 September 2024.