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NCT Number: NCT06906081

Finerenone Treatment for Diabetic Cardiovascular Autonomic Neuropathy: the FibroCAN Study

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.

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Key information

Conditions

Cardiovascular Autonomic Neuropathy Diabetes Complications Diabetes Mellitus Diabetes Mellitus, Type 2 Diabetic Neuropathies Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nervous System Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Peripheral Nervous System Diseases Type 2 Diabetes

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Steno Diabetes Center Northern Denmark, Gistrup, Denmark

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Kerendia (Finerenone, BAY94-8862)

Drug

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.

Placebo

Drug

Placebo tablets matching BAY94-8862 are administered orally.

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

Other outcomes

  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  21. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Christian Stevns Hansen, Ph.D, MD

CONTACT

[email protected]

+4561671618

Peter Rossing, Professor, MD

CONTACT

[email protected]

+4530913383

Sponsors and collaborators

Lead sponsor

Peter Rossing

Other

Collaborators

  • Aarhus University Hospital
  • Steno Diabetes Center Nordjylland

Registry information

Acronym: FibroCAN

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Apr 2, 2025
Registry last updated
May 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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