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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-516597-30-00 | EU Trial (CTIS) Number |
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| Name | Class |
|---|---|
| Steno Diabetes Center Nordjylland | OTHER |
| Aarhus University Hospital | OTHER |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Finerenone (active) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Between-group (finerenone vs. placebo) difference in changes on the CART E/I ratio | Measured by vagus device | 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 | Description | Time Frame |
|---|---|---|
| Between-group (finerenone vs. placebo) difference in changes on the CART R/S ratio | R/S ratio (CART). Measured by Vagus device. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Between-group (finerenone vs. placebo) differences in changes on inflammation markers | Olink inflammation markers will be measured with PCR. | 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 markers of retinopathy |
To be included in this study the participants must fulfill the following inclusion criteria.
Exclusion criteria Participants will be excluded in one or more of the following criteria are met.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Peter Rossing, Professor, MD | Contact | +4530913383 | peter.rossing@regionh.dk | |
| Christian Stevns Hansen, Ph.D, MD | Contact | +4561671618 | christian.stevns.hansen@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Peter Rossing, Professor, MD | Steno Diabetes Center Copenhagen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Steno Diabetes Center Northern Denmark | Recruiting | Gistrup | 9260 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41130701 | Derived | 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. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 31, 2024 | Dec 19, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003929 | Diabetic Neuropathies |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C576501 | finerenone |
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| Placebo | Drug | Placebo tablets matching BAY94-8862 are administered orally. |
|
Valsalva manoeuvre (CART). Measured by Vagus device. |
| 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 | 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. | 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. | Measured by vagus device as low and high frequency power in the unit milliseconds squared. | 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 | Serum PRO-C6 and PRO-C3 assessed by ELISA. | 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 | Pro-C6 by immunostaining | 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 | C3M by immunostaining | From baseline to the end of treatment at 78 weeks. Tested at week 0, 36 and 78 |
Markers of retinopathy (nonproliferativ/proliferative retinopathy and retinal nerve fibre layer thickness by optical coherence tomography) |
| From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78. |
| Between-group (finerenone vs. placebo) differences in changes on markers of corneal neuropathy by CNFD | 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. | From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78. |
| Between-group (finerenone vs. placebo) differences in changes on markers of corneal by neuropathy by CNBD | 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. | From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78. |
| Between-group (finerenone vs. placebo) differences in changes on markers of corneal neuropathy by DCF, DCP, NCF and NCP | 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. | From enrollement to the end of treatment at 78 weeks. Tested at week 0, week 36 and week 78. |
| Between-group (finerenone vs. placebo) difference on Cardiac vagal tone | Measured with eMotion Faros | 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 questionnaires for painful and painless neuropathy DN4 | 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. | 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 questionnaires for painful and painless neuropathy MNSI | The following neuropathy questionnaires will be used to assess peripheral neuropathy: Michigan Neuropathy Screening Instrument (MNSI) with ≥ 4 a cut-off. | 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 orthostatic blood pressure testing | 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. | 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 Sudomotor function of the skin in hands and feet (Sudoscan) | Measured with: (Sudoscan) | 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 of questionnaires for autonomic neuropathy Compass-31 | Measured with compass-31. | 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 of questionnaires for autonomic neuropathy GCSI | Measured with GCSI. | 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 of sural nerve conduction and amplitude (DPNCheck) | 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. | 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 of vibration sensation threshold (Biothesiometry) | 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. | 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 of pain sensation | 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. | 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 of light touch sensation | 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. | 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 of cold and warm sensation of foot and lower leg | 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. | 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 of ancle and patella reflexes (Reflex hammer) | Ancle and patella reflexes will be perform using a reflex hammer on both sides. | 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 of intraepidermal nerve fiber density (IENFD) | Intraepidermal nerve fiber density (IENFD quantified following international guidelines | From baseline to the end of treatment at 78 weeks. Tested at screening, week 0, week 36 and week 78 |
| The association between serum fibrosis markers and level of peripheral neuropathy in type 2 diabetes | Measurement of baseline fibrosis markers in serum and in skin samples and compare to level of peripheal neuropathy measured at baseline | Data analysis after baseline sampling |
| The association between serum fibrosis markers and level of autonomic neuropathy in type 2 diabetes | Measurement of baseline fibrosis markers in serum and compare to level of autonomic neuropathy measured at baseline | Data analysis after baseline sampling |
| Steno Diabetes Center Copenhagen | Not yet recruiting | Herlev | 2730 | Denmark |
|
| D004700 | Endocrine System Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |