Finerenone Treatment for Diabetic Cardiovascular Autonomic Neuropathy: the FibroCAN Study (FibroCAN)

May 23, 2025 updated by: Peter Rossing

Diabetic neuropathy is a serious and common complication of diabetes that currently has no cure. One form of this condition is cardiovascular autonomic neuropathy (CAN), which affects about 20% of people with diabetes-an estimated 100 million people worldwide. CAN is a significant risk factor for death and health problems like heart disease and kidney damage, and may contribute to the high rates of cardiovascular-related deaths in people with diabetes.

This study is a double-blind, randomized, placebo-controlled, two-center trial. The study aims to test whether finerenone can treat cardiovascular autonomic neuropathy in patients with type 2 diabetes. The trial will evaluate the effects of 78 weeks of treatment with finerenone or a placebo, assigned randomly in a 1:1 ratio, on early-stage cardiovascular autonomic neuropathy. The trial will include 100 participants with type 2 diabetes. Additionally, the study will investigate how the treatment impacts other types of neuropathy and related pathological mechanisms.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Gistrup, Denmark, 9260
        • Recruiting
        • Steno Diabetes Center Northern Denmark
        • Contact:
          • Asbjørn Mohr Drewes, MD, professor
          • Phone Number: +45 99321111
          • Email: amd@rn.dk
        • Contact:
        • Principal Investigator:
          • Asbjørn Mohr Drewes, MD, professor
      • Herlev, Denmark, 2730
        • Not yet recruiting
        • Steno Diabetes Center Copenhagen
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Christian Stevns Hansen, PhD, MD
        • Principal Investigator:
          • Peter Rossing, MD, professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

To be included in this study the participants must fulfill the following inclusion criteria.

  • Given informed consent
  • Type 2 diabetes defined by WHO criteria
  • Aged 40 ≥ at inclusion
  • Pathological E/I ratio (Mean value of three measures)

Exclusion criteria Participants will be excluded in one or more of the following criteria are met.

  • No CAN (no abnormal CARTs)
  • Definite CAN (more than one abnormal CART)
  • HbA1C >100 mmol/L
  • Treatment with potassium-sparing diuretics (amiloride) or MRAs e.g., spironolactone or eplerenone which cannot be discontinued 4 weeks prior to screening visit. The patient's primary physician, who is not involved in this study, will determine if discontinuation is possible.
  • Atrial fibrillation/flutter
  • Congestive heart failure (NYHA class 3-4)
  • History of cardiac arrhythmia
  • Severe forms of respiratory disease including asthma and COPD
  • Any nondiabetic cause of neuropathy
  • All female subjects of childbearing potential (WOCBP) must have a negative result of a highly sensitive urine HCG (pregnancy test) performed at screening. Subjects of childbearing potential must agree to use a highly effective form of contraception throughout the duration of the study (list of definition on WOCBP and accepted contraception in appendix A).
  • Severe hepatic impairment
  • Lactose intolerance
  • Breastfeeding
  • Nephropathy requiring dialysis
  • Beta-blocker-use
  • Hyperkalemia at screening visit (plasma potassium >4.8 mmol/l)
  • eGFR < 25 ml/min/1.73m2
  • Potassium plasma > 4.8 mmol/l (at randomization)
  • Treatment with strong CYP3A4-inhibitors (e.g. Itraconazol, ketoconazol, ritonavir, cobicistat, clarithromycin) which cannot be discontinued 4 weeks prior to screening visit
  • Treament with moderate to strong CYP3A4-induceres (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort or efavirenz) which cannot be discontinued 4 weeks prior to screening visit
  • Have received chemotherapeutic treatment within last 12 months
  • Grapefruit consumption that cannot be discontinued during the study period
  • Inability to complete study protocol, assessed to investigator
  • Not able to read, write and/or understand Danish

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo tablets matching BAY94-8862 are administered orally.
Experimental: Finerenone (active)
Drug: Kerendia (Finerenone, BAY94-8862)

Titration of finerenone will be based on baseline eGFR. Participants with eGFR > 60 mL/min/1.73m² will start on a 20mg dosage. Medication dosage will be increased to 40 mg after one month if serum potassium < 4.8 mmol/l. If side effects occur at any dosage, the dosage will be reduced to the previous level.

Participants with eGFR < 60 and >25 Participants with eGFR < 60 mL/min/1.73m² (and eGFR < 25 mL/min/1.73m²) will start on a 10mg dosage. Medication dosage will be increased to 20 mg after one month if serum potassium < 4.8 mmol/l. Subsequently, Medication dosage will be increased to 40 mg after an additional one month if serum potassium < 4.8 mmol/l. If side effects occur at any dosage, the dosage will be reduced to the previous level.

Finerenone is administered orally as immediate release tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Between-group (finerenone vs. placebo) difference in changes on the CART E/I ratio
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured by vagus device
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Between-group (finerenone vs. placebo) difference in changes on the CART R/S ratio
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
R/S ratio (CART). Measured by Vagus device.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes on the CART Valsalva manoeuvre.
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Valsalva manoeuvre (CART). Measured by Vagus device.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) differences in changes on heart rate variability (HRV) by SDNN and RMSSD
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured by vagus device as SDNN (Standard Deviation of Normal-to-Normal interbeat) intervals and RMSSD (Root Mean Square of Successive Differences between normal heartbeats). SDNN and RMSSD is measured in milliseconds.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) differences in changes on heart rate variability (HRV) by high and low frequency power.
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured by vagus device as low and high frequency power in the unit milliseconds squared.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) differences in changes on fibrosis markers in serum
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78. Skin biopsies on week 0, week 36 and week 78.
Serum PRO-C6 and PRO-C3 assessed by ELISA.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78. Skin biopsies on week 0, week 36 and week 78.
Between-group (finerenone vs. placebo) differences in changes on fibrosis markers in skin biopsies by PRO-C6
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78
Pro-C6 by immunostaining
From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78
Between-group (finerenone vs. placebo) differences in changes on fibrosis markers in skin biopsies by C3M
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78
C3M by immunostaining
From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Between-group (finerenone vs. placebo) differences in changes on inflammation markers
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Olink inflammation markers will be measured with PCR.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) differences in changes on markers of retinopathy
Time Frame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Markers of retinopathy (nonproliferativ/proliferative retinopathy and retinal nerve fibre layer thickness by optical coherence tomography)
From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Between-group (finerenone vs. placebo) differences in changes on markers of corneal neuropathy by CNFD
Time Frame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Overall to quantify the severity of small nerve fibre damage by confocal corneal microscopy. Quantified by corneal nerve fiber density (CNFD) measured in fibers per mm2.
From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Between-group (finerenone vs. placebo) differences in changes on markers of corneal by neuropathy by CNBD
Time Frame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.

Overall to quantify the severity of small nerve fibre damage by confocal corneal microscopy.

Quantified including corneal nerve branch density (CNBD) measured in branches per mm2.
From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Between-group (finerenone vs. placebo) differences in changes on markers of corneal neuropathy by DCF, DCP, NCF and NCP
Time Frame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Overall to quantify the severity of small nerve fibre damage by confocal corneal microscopy. Quantified including corneal nerve fiber length (CNFL), dendritic cells with contact to nerve fiber (DCF), dendritic cells without contact to nerve fiber (DCP), non-dendritic cells with contact to nerve fiber (NCF) and non-dendritic cells without contact to nerve fiber (NCP). All measured in cells per mm2.
From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
Between-group (finerenone vs. placebo) difference on Cardiac vagal tone
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured with eMotion Faros
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes on questionnaires for painful and painless neuropathy DN4
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78

The following neuropathy questionnaires will be used to assess peripheral neuropathy:

- The Douleur Neuropathique 4 (DN4) to assess painful peripheral neuropathy with a cut-off ≥ 4.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes on questionnaires for painful and painless neuropathy MNSI
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78

The following neuropathy questionnaires will be used to assess peripheral neuropathy:

Michigan Neuropathy Screening Instrument (MNSI) with ≥ 4 a cut-off.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes on orthostatic blood pressure testing
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Orthostatic hypotension will be defined as decline in systolic blood pressure ≥ 20 mmHg or diastolic blood pressure ≥ 10 mmHg or a decrease in systolic blood pressure to < 90. From position change from lying to standing.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes on Sudomotor function of the skin in hands and feet (Sudoscan)
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured with: (Sudoscan)
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of questionnaires for autonomic neuropathy Compass-31
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured with compass-31.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of questionnaires for autonomic neuropathy GCSI
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Measured with GCSI.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of sural nerve conduction and amplitude (DPNCheck)
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Nerve conduction velocity and amplitude of the sural nerve will be assessed the average of three measures on both the left and right leg by use of the NC-StatR DPNCheck (NeuroMetrix, Inc., Waltham, USA). Age- and height-stratified perception thresholds will be applied.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of vibration sensation threshold (Biothesiometry)
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Vibration perception threshold (VPT) will be measured by using biothesiometry (Bio-medical instruments, Ohio, USA) applied to the distal tip of the first toe on both feet. Cut-off above 25 V and age-sex-height specific cut-offs was applied (38, 39). Biothesiometry measurements will be repeated three times and averaged of the measures will be used.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of pain sensation
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Pain sensation will be assessed by pinprick (Neuropen, Owen Mumford Ltd, Oxford, UK). Pinpricks will be applied proximal to the nail on the first dorsal, third and fifth toes on each foot. DPN will be defined as no pain at any tested location.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of light touch sensation
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Ten-gram monofilament (Neuropen, Owen Mumford Ltd, Oxford, UK) will be applied three times at four points on the plantar aspect of the foot (first toe, proximal to the first toe, third toe and fifth toe) in addition to the proximal to the nail on the first dorsal, third and fifth toes on each foot. All measures will be obtained on both feet. DPN will be defined as absence of sensation at all locations.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of cold and warm sensation of foot and lower leg
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Thermal sensation (25°C and 40°C) will be assessed by applying metal rolls bilaterally on the dorsal side of the first toe, dorsum of the foot and the anterior part of the low leg from 10 centimeter above the lateral malleolus and 10 centimeter proximately by Rolltemp-II (Somedic SenseLab AB). All measures will be obtained on both legs. Abnormal sensation will be defined as bilateral abnormalities at the toes, either with or without an abnormal sensation of the foot and leg.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of ancle and patella reflexes (Reflex hammer)
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Ancle and patella reflexes will be perform using a reflex hammer on both sides.
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 12, week 24, week 36, week 52 and week 78
Between-group (finerenone vs. placebo) difference in changes of intraepidermal nerve fiber density (IENFD)
Time Frame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 36 and week 78
Intraepidermal nerve fiber density (IENFD quantified following international guidelines
From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 36 and week 78
The association between serum fibrosis markers and level of peripheral neuropathy in type 2 diabetes
Time Frame: Data analysis after baseline sampling
Measurement of baseline fibrosis markers in serum and in skin samples and compare to level of peripheal neuropathy measured at baseline
Data analysis after baseline sampling
The association between serum fibrosis markers and level of autonomic neuropathy in type 2 diabetes
Time Frame: Data analysis after baseline sampling
Measurement of baseline fibrosis markers in serum and compare to level of autonomic neuropathy measured at baseline
Data analysis after baseline sampling

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peter Rossing

Collaborators

Aarhus University Hospital
Steno Diabetes Center Nordjylland

Investigators

  • Principal Investigator: Peter Rossing, Professor, MD, Steno Diabetes Center Copenhagen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2025

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

February 3, 2025

First Submitted That Met QC Criteria

March 25, 2025

First Posted (Actual)

April 2, 2025

Study Record Updates

Last Update Posted (Actual)

May 25, 2025

Last Update Submitted That Met QC Criteria

May 23, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-516597-30-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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