Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-03-31 @ 3:19 PM
Study NCT ID:
NCT07471802
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-24
First Post:
2026-03-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Monitoring of the Sympathetic/Vagal Balance Through Multiparametric Analysis of Heart Rate Variability (HRV)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}, {'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}, {'id': 'D059347', 'term': 'Cardio-Renal Syndrome'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015716', 'term': 'Electrocardiography, Ambulatory'}], 'ancestors': [{'id': 'D004562', 'term': 'Electrocardiography'}, {'id': 'D006334', 'term': 'Heart Function Tests'}, {'id': 'D003935', 'term': 'Diagnostic Techniques, Cardiovascular'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D004568', 'term': 'Electrodiagnosis'}, {'id': 'D018670', 'term': 'Monitoring, Ambulatory'}, {'id': 'D008991', 'term': 'Monitoring, Physiologic'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 150}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-03-25', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2031-09-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-20', 'studyFirstSubmitDate': '2026-03-10', 'studyFirstSubmitQcDate': '2026-03-10', 'lastUpdatePostDateStruct': {'date': '2026-03-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2031-03-25', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Assessment of the sympathetic/vagal balance at baseline', 'timeFrame': '24 hours', 'description': "All outcomes (primary and secondary) will be evaluated at rest, during daily activity and NREM sleep, with short-term (2- and 5-minute) Heart Rate Variability (HRV) analysis from 24-hour Holter recordings, with Kubios Scientific, a gold-standard HRV software tool for research, providing automatic calculation of multiple parameters in the time domain (TD), frequency domain (FD), with non-linear (NL) methods, and automatic time-varying computation of the parasympathetic (PNSi), sympathetic (SNSi), and Baevsky stress (BSTRi) indices, for faster and more comprehensive assessment of cardiac autonomic modulation (the PNS index ranges between -1 and 1 for 68% of the adult population at rest, and similarly scaled SNS index values outside the -1 to 1 range indicate higher or lower than average sympathetic activity) \\[1\\]. Tables reporting the laboratory's average age-related normal values for all parameters measured in daily activity and NREM sleep are available \\[2\\]. (Ref. moved to Citations)"}, {'measure': 'Changes the sympathetic/vagal balance during pharmacological treatment with SGLT2 inhibitors', 'timeFrame': '24 months', 'description': 'Outcome 2 will be assessed with Kubios, measuring the same HRV parameters and indices from the 24-hour follow-up Holter recordings. Changes of the sympathetic/vagal balance will be individually evaluated in each condition (rest, daily activity, and NREM sleep) and compared with the baseline values.\n\nNo score on a scale will be used.'}], 'secondaryOutcomes': [{'measure': 'Evaluation of diabetic cardiovascular autonomic neuropathy', 'timeFrame': '24 months', 'description': 'As for the primary outcome measures, outcome 3 will be assessed with Kubios, measuring the same HRV parameters and indices from the 24-hour baseline and follow-up Holter recordings. The sympathetic/vagal balance will be individually evaluated in each condition (rest, daily activity, and NREM sleep) and compared with the baseline values at each control to identify which HRV parameters/indices can be more sensitive markers for early identification of the onset (or worsening) of diabetic cardiovascular autonomic neuropathy.'}, {'measure': 'Correlation between improvement of heart failure or cardiorenal disease', 'timeFrame': '24 months', 'description': 'Assessment of the possible correlation between improvement of heart failure or cardiorenal disease'}, {'measure': 'Detection of improvement or normalization of cardiac autonomic balance', 'timeFrame': '24 months', 'description': 'Outcome 5 will be assessed with Kubios, measuring the same HRV parameters and indices from the 24-hour baseline and follow-up Holter recordings. The comprehensive assessment of cardiac autonomic modulation will be individually performed in each condition (rest, daily activity, and NREM sleep) by comparing the sensitivity of TD, FD, and NL methods, with that provided by the automatic time-varying computation of the PNSi, SNSi, and BSTRi indices. Any change of the cardiac autonomic modulation toward a prevalence of the parasympathetic tone (either for an increase of vagal modulation, or a decrease of sympathetic modulation, or both), will be considered a positive outcome on cardiac autonomic function \\[3-5\\].'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Diabete Type 2', 'Heart Failure', 'Kidney Disease, Chronic', 'Cardiorenal Syndrome']}, 'referencesModule': {'references': [{'pmid': '24054542', 'type': 'BACKGROUND', 'citation': 'Tarvainen MP, Niskanen JP, Lipponen JA, Ranta-Aho PO, Karjalainen PA. Kubios HRV--heart rate variability analysis software. Comput Methods Programs Biomed. 2014;113(1):210-20. doi: 10.1016/j.cmpb.2013.07.024. Epub 2013 Aug 6.'}, {'type': 'BACKGROUND', 'citation': 'Brisinda D, Picerni M, Fenici P, and Fenici R, "Rapid assessment of cardiac autonomic modulation and adaptive stress responses: Automatic calculation of time-varying parasympathetic, sympathetic, and Baevsky stress indexes," Brain & Heart., vol. 2, no. 4, p. 3503, 2024, doi: 10.36922/bh.3503.'}, {'pmid': '35949125', 'type': 'BACKGROUND', 'citation': 'Balcioglu AS, Celik E, Sahin M, Gocer K, Aksu E, Aykan AC. Dapagliflozin Improves Cardiac Autonomic Function Measures in Type 2 Diabetic Patients with Cardiac Autonomic Neuropathy. Anatol J Cardiol. 2022 Nov;26(11):832-840. doi: 10.5152/AnatolJCardiol.2022.1934.'}, {'pmid': '39834729', 'type': 'BACKGROUND', 'citation': 'Zhou L, Niu M, Chen W, Hu Q, Chen Y, Geng X, Gu J. Effects of dapagliflozin on heart rate variability, cardiac function, and short-term prognosis in early-onset post-myocardial infarction heart failure. Front Cardiovasc Med. 2025 Jan 6;11:1490316. doi: 10.3389/fcvm.2024.1490316. eCollection 2024.'}, {'pmid': '39436317', 'type': 'BACKGROUND', 'citation': 'Dimitriadis K, Pitsiori D, Alexiou P, Pyrpyris N, Sakalidis A, Beneki E, Iliakis P, Tatakis F, Theofilis P, Tsioufis P, Konstantinidis D, Aggeli K, Tsioufis K. Modulating Sympathetic Nervous System With the Use of SGLT2 Inhibitors: Where There Is Smoke, There Is Fire? J Cardiovasc Pharmacol. 2025 Jan 1;85(1):12-20. doi: 10.1097/FJC.0000000000001644.'}]}, 'descriptionModule': {'briefSummary': 'The autonomic nervous system (ANS) plays a crucial role in cardiovascular regulation by modulating heart rate in response to endogenous and environmental stimuli. Heart rate variability (HRV) analysis has been widely used as a non-invasive tool to assess autonomic function and the balance between sympathetic and parasympathetic activity. Although the physiological interpretation of some HRV parameters remains debated-particularly the low-frequency (LF) spectral component as an index of sympathetic activation-HRV remains an important method for evaluating autonomic cardiovascular control.\n\nReduced HRV has been associated with adverse outcomes in several pathological conditions and physiologically declines with aging, mainly due to progressive neuronal loss at central and spinal levels. Among conditions characterized by autonomic dysfunction, cardiovascular autonomic neuropathy (CAN) represents a common complication of diabetes mellitus (DM) and metabolic syndrome. CAN, defined as impairment of autonomic control of the cardiovascular system, develops early in the disease course and is associated with increased mortality and a higher risk of cardiovascular and renal complications.\n\nSodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed as glucose-lowering agents, have demonstrated significant cardiovascular and renal protective effects beyond glycemic control. Growing evidence suggests that these drugs exert sympathoinhibitory effects that may be beneficial not only in diabetic patients but also in conditions characterized by sympathetic overactivity. Preclinical and clinical studies have shown that SGLT2i influence autonomic regulation, including sympathetic control of renal function, with reported improvements in 24-hour blood pressure regulation and HRV parameters.\n\nLarge randomized trials have further confirmed the cardioprotective effects of SGLT2i therapy. Studies such as EMBODY, EMPEROR-Reduced, and EMPEROR-Preserved have demonstrated improvements in HRV indices and significant reductions in cardiovascular death and hospitalization for heart failure, irrespective of diabetic status.\n\nDespite these findings, the mechanisms underlying these benefits remain incompletely understood. While reduced sympathetic activity has been proposed as a key mechanism, emerging evidence suggests that SGLT2i may also enhance vagal modulation. Therefore, the present study aims to investigate, in a larger population, the effects of SGLT2i therapy on sympathovagal balance using both spectral HRV parameters and additional indices, including the parasympathetic nervous system index (PNSi), sympathetic nervous system index (SNSi), and the Baevsky Stress Index.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Outpatient patients with:\n\n* Type 2 DM, with or without heart failure and/or chronic kidney disease, with a clinical indication to undergo HOLTER ECG monitoring to exclude or quantify concomitant autonomic dysfunction.\n* Patients with Cardiomyopathy, with heart failure or cardiorenal syndrome, with a cardiological indication to undergo HOLTER ECG monitoring to exclude or quantify signs attributable to ischemic heart disease and/or cardiac arrhythmias.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age over 18 years;\n* Signed informed consent;\n* in Sinus rhythm;\n* Patients for whom HOLTER ECG monitoring is clinically indicated, to early identify the possible onset or progression of diabetic autonomic neuropathy, or ischemic changes, or potentially arrhythmogenic electrophysiological alterations;\n* On optimized pharmacological treatment according to clinical practice, naïve to SGLT2 inhibitor therapy, prescribed according to the (1A) recommendations of the ESC 2023 guidelines.\n\nExclusion Criteria:\n\n* Patients with atrial fibrillation or other arrhythmic burden incompatible with accurate HRV analysis;\n* Pacemaker or ICD carriers;\n* Immunodeficient patients or patients at risk of developing infections.'}, 'identificationModule': {'nctId': 'NCT07471802', 'acronym': 'GLIFO-HRV', 'briefTitle': 'Monitoring of the Sympathetic/Vagal Balance Through Multiparametric Analysis of Heart Rate Variability (HRV)', 'organization': {'class': 'OTHER', 'fullName': 'Fondazione Policlinico Universitario Agostino Gemelli IRCCS'}, 'officialTitle': 'Monitoring of the Sympathetic/Vagal Balance Through Multiparametric Analysis of Heart Rate Variability (HRV) in Patients With Type 2 Diabetes Mellitus (Type 2 DM), With or Without Heart Failure and/or Chronic Kidney Disease, or Cardiomyopathy, With Heart Failure and/or Cardio-renal Syndrome, All Receiving Optimized Pharmacological Treatment, Including a Sodium-Glucose Co-transporter 2 Inhibitor (SGLT2i).', 'orgStudyIdInfo': {'id': '27089'}}, 'armsInterventionsModule': {'interventions': [{'name': 'HOLTER ECG monitoring', 'type': 'DIAGNOSTIC_TEST', 'description': 'Monitoring of the sympathetic/vagal balance through multiparametric analysis of heart rate variability (HRV) using 24 hours ECG HOLTER'}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Donatella Brisinda, MD', 'role': 'CONTACT', 'email': 'donatella.brisinda@policlinicogemelli.it', 'phone': '+390630158195'}], 'overallOfficials': [{'name': 'Donatella Brisinda, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Fondazione Policlinico Universitario Agostino Gemelli IRCCS'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fondazione Policlinico Universitario Agostino Gemelli IRCCS', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}