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.


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