Finerenone Treatment for Diabetic Cardiovascular Autonomic Neuropathy: the FibroCAN Study

Обзор

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.

Вмешательства

• Препарат 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 aft
• Препарат Placebo
  Placebo tablets matching BAY94-8862 are administered orally.

Первичные конечные точки

• Between-group (finerenone vs. placebo) difference in changes on the CART E/I ratio [Срок оценки: 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]

Вторичные конечные точки (7)

• Between-group (finerenone vs. placebo) difference in changes on the CART R/S ratio [Срок оценки: 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. [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Дания · 2 центра

• Steno Diabetes Center Northern Denmark — Gistrup
• Steno Diabetes Center Copenhagen — Herlev

Публикации

• Bitsch Poulsen M, Okdahl T, Buciek JH, Drewes AM, Karlsson P, Ahluwalia TS, Brock B, Brock C, Rossing P, Hansen CS. Protocol for the FibroCAN study: a randomised controlled trial of finerenone treatment for early-stage cardiovascular autonomic neuropathy in type 2 diabetes. BMJ Open. 2025 Oct 23;15(10):e101074. doi: 10.1136/bmjopen-2025-101074. PMID 41130701

Идентификаторы

NCT: NCT06906081 · 2024-516597-30-00 · 2024-516597-30-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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