Clinical trial NCT06906081: Finerenone Treatment for Diabetic Cardiovascular Autonomic Neuropathy: the FibroCAN Study
Official title: Finerenone Treatment for Diabetic Cardiovascular Autonomic Neuropathy: the FibroCAN Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cardiovascular Autonomic Neuropathy
Type 2 Diabetes
Diabetic Neuropathies
Keywords: Mineralocorticoid receptor antagonist (MRA)
Cardiovascular autonomic neuropathy
Type 2 Diabetes
Diabetic Neuropathy
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Steno Diabetes Center Nordjylland
name: Aarhus University Hospital
First posted: 2025-04-02
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Between-group (finerenone vs. placebo) difference in changes on the CART E/I ratio
timeFrame: 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 outcomes:
measure: Between-group (finerenone vs. placebo) difference in changes on the CART R/S ratio
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes on the CART Valsalva manoeuvre.
timeFrame: 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
measure: Between-group (finerenone vs. placebo) differences in changes on heart rate variability (HRV) by SDNN and RMSSD
timeFrame: 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
measure: Between-group (finerenone vs. placebo) differences in changes on heart rate variability (HRV) by high and low frequency power.
timeFrame: 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
measure: Between-group (finerenone vs. placebo) differences in changes on fibrosis markers in serum
timeFrame: 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.
measure: Between-group (finerenone vs. placebo) differences in changes on fibrosis markers in skin biopsies by PRO-C6
timeFrame: From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78
measure: Between-group (finerenone vs. placebo) differences in changes on fibrosis markers in skin biopsies by C3M
timeFrame: From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78
Other outcomes:
measure: Between-group (finerenone vs. placebo) differences in changes on inflammation markers
timeFrame: 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
measure: Between-group (finerenone vs. placebo) differences in changes on markers of retinopathy
timeFrame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
measure: Between-group (finerenone vs. placebo) differences in changes on markers of corneal neuropathy by CNFD
timeFrame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
measure: Between-group (finerenone vs. placebo) differences in changes on markers of corneal by neuropathy by CNBD
timeFrame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
measure: Between-group (finerenone vs. placebo) differences in changes on markers of corneal neuropathy by DCF, DCP, NCF and NCP
timeFrame: From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78.
measure: Between-group (finerenone vs. placebo) difference on Cardiac vagal tone
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes on questionnaires for painful and painless neuropathy DN4
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes on questionnaires for painful and painless neuropathy MNSI
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes on orthostatic blood pressure testing
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes on Sudomotor function of the skin in hands and feet (Sudoscan)
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of questionnaires for autonomic neuropathy Compass-31
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of questionnaires for autonomic neuropathy GCSI
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of sural nerve conduction and amplitude (DPNCheck)
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of vibration sensation threshold (Biothesiometry)
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of pain sensation
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of light touch sensation
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of cold and warm sensation of foot and lower leg
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of ancle and patella reflexes (Reflex hammer)
timeFrame: 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
measure: Between-group (finerenone vs. placebo) difference in changes of intraepidermal nerve fiber density (IENFD)
timeFrame: From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 36 and week 78
measure: The association between serum fibrosis markers and level of peripheral neuropathy in type 2 diabetes
timeFrame: Data analysis after baseline sampling
measure: The association between serum fibrosis markers and level of autonomic neuropathy in type 2 diabetes
timeFrame: Data analysis after baseline sampling
Locations:
city: Gistrup
country: Denmark
facility: Steno Diabetes Center Northern Denmark
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Peter Rossing, Professor, MD
role: PRINCIPAL_INVESTIGATOR
References: