FINERENONE for Diabetic cardiovascular autonomic neuropathy

Inclusion criteria

• {"criterion_text":"- Given informed consent\n- Type 1 diabetes or type 2 diabetes defined by WHO criteria\n- Aged 40 to 79 years at inclusion\n- Pathological E/I ratio (Mean value of three measures) or a pathological E/I ratio and another pathological CART"}

Exclusion criteria

• {"criterion_text":"- No CAN (no abnormal CARTs)\n- Server forms of respiratory disease including asthma and COPD\n- Any nondiabetic cause of neuropathy\n- 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).\n- Not able to read, write and/or understand Danish\n- Breastfeeding\n- Nephropathy requiring dialysis\n- Beta-block treatment not paused ≥24 hours prior to cardiovascular reflex testing, or if pausing treatment was not deemed safe by the investigator\n- Hyperkalemia at sceening visit (plasma potassium >4.8 mmol/l)\n- eGFR < 25 ml/min/1.73m2\n- Plasma potassium > 4.8 mmol/l (at randomization)\n- have received chemotherapeutic treatment within last 12 months\n- Treatment with strong CYP3A4-inhibitors (e.g. Itraconazol, ketoconazol, ritonavir, cobicistat, clarithromycin) which cannot be discontinued 4 weeks prior to screening visit\n- Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption\n- Grapefruit consumption that cannot be discontinued during the study period\n- 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\n- Severe hepatic impairment\n- inability to complete study protocol, assessed to investigator\n- Three pathological CARTs\n- HbA1C >100 mmol/mol\n- 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\n- Atrial fibrillation/flutter\n- Congestive heart failure (NYHA class 3-4)\n- History of cardiac arrhythmia"}

Primary endpoints

• {"endpoint_text":"- The CART E/I ratio (by the Vagustm device)","definition_or_measurement_approach":"Measured as the CART E/I ratio using the Vagustm device."}

Secondary endpoints

• {"endpoint_text":"- Cardiovascular reflex tests: R/S ratio, Valsalva manoeuvre (CARTs)","definition_or_measurement_approach":"Cardiovascular reflex tests (CARTs) including R/S ratio and Valsalva manoeuvre as standard CART measures."}
• {"endpoint_text":"- HRV indices (SDNN, RMSSD, Low and high-frequency power) (by the Vagustm device)","definition_or_measurement_approach":"Heart rate variability indices (SDNN, RMSSD, LF and HF power) measured using the Vagustm device."}
• {"endpoint_text":"- Fibrosis markers (serum PRO-C6 and C3M assessed by ELISA)","definition_or_measurement_approach":"Serum fibrosis markers PRO-C6 and C3M assessed by ELISA."}
• {"endpoint_text":"- Fibrosis markers in skin biopsies (Pro-C6 and C3M by immunostaining (Only week 0, 36, 78)","definition_or_measurement_approach":"Fibrosis markers Pro-C6 and C3M assessed in skin biopsies by immunostaining at weeks 0, 36 and 78."}

Denmark

Earliest CTIS Part Ii Submission Date

08-11-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

403

Number Of Sites

2

Number Of Participants

100

Primary sponsor

Full Name

Steno Diabetes Center Copenhagen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"BioXpedia","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Industry"}
• {"country":"Denmark","full_name":"Danish Pain Research Center","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Educational Institution"}
• {"country":"Denmark","full_name":"GCP-enheden ved Københavns Universitetshospital","duties_or_roles":"sponsorDuties codes: [1]","organisation_type":"Health care"}
• {"country":"Denmark","full_name":"Stenolab","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Health care"}
• {"country":"United States","full_name":"University of Michigan","duties_or_roles":"sponsorDuties codes: [13]","organisation_type":"Educational Institution"}
• {"country":"Denmark","full_name":"University of Copenhagen","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Educational Institution"}
• {"country":"Denmark","full_name":"Department of biochemistry","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Health care"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}