Ignite Creation Date:
2025-12-24 @ 11:39 PM
Ignite Modification Date:
2025-12-25 @ 9:30 PM
Study NCT ID:
NCT06140251
Status:
UNKNOWN
Last Update Posted:
2023-11-18
First Post:
2023-11-05
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Investigation of Biomarker Response to SGLT2 Inhibition in Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077203', 'term': 'Sodium-Glucose Transporter 2 Inhibitors'}], 'ancestors': [{'id': 'D045504', 'term': 'Molecular Mechanisms of Pharmacological Action'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}, {'id': 'D007004', 'term': 'Hypoglycemic Agents'}, {'id': 'D045505', 'term': 'Physiological Effects of Drugs'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Saliva samples will be collected at both time points using a commercially available kit (SalivaBio Oral Swab Device, Salimetrics LLC, Carlsbad, CA, USA). Blood samples for novel biomarkers will be undergo centrifugation at 2500 g for 10 min with subsequent aliquoting and storage of plasma at -80 ∘C until required. Enzyme-linked immunosorbent assay (ELISA) based assays will be used to quantify levels of novel proteins as detailed below.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 68}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-08-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2025-05-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-11-15', 'studyFirstSubmitDate': '2023-11-05', 'studyFirstSubmitQcDate': '2023-11-15', 'lastUpdatePostDateStruct': {'date': '2023-11-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-11-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-09-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling.', 'timeFrame': '26 weeks.', 'description': 'Correlation of log transformed delta change in novel cardiac biomarkers with global longitudinal strain \\[GLS (%)\\] and left ventricular ejection fraction \\[LVEF (%)\\].'}, {'measure': 'Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling.', 'timeFrame': '26 weeks.', 'description': 'Correlation of log transformed delta change in novel cardiac biomarkers with change in left ventricular end systolic volume index \\[LVESVi (mls/m2)\\], left ventricular end diastolic volume \\[LVEDVi (mls/m2)\\] and left atrial volume \\[LAVi (mls/m2)\\].'}, {'measure': 'Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with qualitive markers of heart failure outcomes.', 'timeFrame': '26 weeks.', 'description': 'Correlation of log transformed delta change in novel cardiac biomarkers with change in Kansas-City Cardiomyopathy Questionnaire (KCCQ).'}, {'measure': 'Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with qualitive markers of heart failure outcomes.', 'timeFrame': '26 weeks.', 'description': 'Correlation of log transformed delta change in novel cardiac biomarkers with change in Change in New York Heart Association (NYHA) score.'}], 'primaryOutcomes': [{'measure': 'To evaluate whether SGLT2 inhibition in heart failure produces changes in novel cardiac biomarkers.', 'timeFrame': '26 weeks', 'description': 'Assessment of changes in levels of novel biomarkers associated with heart failure, cardiac remodeling, or response to SGLT2i, including; KIM-1, IGFBP7, TNFR, IL-6, collagen IV, MMP7, FN1, sST2, LRG1, Tetranectin, collagen XIV (Olink and ELISA based analysis). Additional novel biomarkers may be added to this investigatory panel as the trial continues.'}], 'secondaryOutcomes': [{'measure': 'To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography.', 'timeFrame': '26 weeks', 'description': 'Changes in global longitudinal strain (GLS) (%) and left ventricular systolic function \\[LVEF (%)\\] as assessed on strain echocardiography.'}, {'measure': 'To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography.', 'timeFrame': '26 weeks', 'description': 'Change in left ventricular end systolic volume index \\[LVESVi (mls/m2)\\], left ventricular end diastolic volume \\[LVEDVi (mls/m2)\\] and left atrial volume \\[LAVi (mls/m2)\\].'}, {'measure': 'To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by diastolic parameters on echocardiography.', 'timeFrame': '26 weeks', 'description': "Change in left ventricular lateral e' (cm/s), septal e' (cm/s) and E/e' ratio obtained from echocardiography."}, {'measure': 'To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.', 'timeFrame': '26 weeks', 'description': 'Changes in standard care cardiac biomarkers following SGLT2 inhibition including, N-terminal prohormone of brain natriuretic peptide \\[NT-proBNP (ng/L)\\] and high sensitivity troponin \\[hs-TnT (ng/L)\\].'}, {'measure': 'To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.', 'timeFrame': '26 weeks', 'description': 'Changes in standard care biomarker of inflammation following SGLT2 inhibition by measurement of serum C-reactive protein \\[CRP (mg/dL).'}, {'measure': 'To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.', 'timeFrame': '26 weeks', 'description': 'Changes in standard care cardiac of diabetic biomarkers following SGLT2 inhibition using measurement of glycosylated haemoglobin \\[HbA1c (mmol/mol)\\].'}, {'measure': 'To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.', 'timeFrame': '26 weeks', 'description': 'Changes in standard care biomarkers of cardiovascular risk following SGLT2 inhibition including lipid profile as assessed by serum cholesterol (mmol/L) and serum low density lipoprotein \\[LDL (mmol/L)\\].'}, {'measure': 'To evaluate changes in qualitative markers of heart failure outcomes.', 'timeFrame': '26 weeks.', 'description': 'Change in New York Heart Association (NYHA) score, classified on a scale I to IV, with a higher number indicating a worse outcome.'}, {'measure': 'To evaluate changes in qualitative markers of heart failure outcomes.', 'timeFrame': '26 weeks.', 'description': 'Change in Kansas-City Cardiomyopathy Questionnaire (KCCQ) score following initiation of SGLT2 inhibition in heart failure. It contains four subdomains: Physical Limitation, Symptom Frequency, Quality of Life, and Social Limitations. Each subdomain provides an individual score from 0 to 100, with 0 denoting the worst and 100 the best possible health status. A change of 5 points on the scale scores, either as a group mean difference or an intra-individual change is defined as clinically significant.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Heart failure', 'Cardiac imaging', 'SGLT2', 'Biomarkers'], 'conditions': ['Heart Failure']}, 'descriptionModule': {'briefSummary': 'This is a 26-week, open label, single-arm prospective evaluation of the effects of sodium glucose cotransporter 2 (SGLT2) inhibition on cardiac biomarkers, myocardial remodeling and patient reported outcomes in heart failure with both impaired and preserved left ventricular fraction.', 'detailedDescription': 'The primary aims of this study are to evaluate whether SGLT2 inhibition in patients with heart failure effects changes in novel cardiac biomarkers. This is an exploratory evaluation of novel cardiac pathways which may serve to establish, as of yet unknown, therapeutic mechanisms of action of SGLT2 inhibition in heart failure. Secondary aims include evaluation of changes in standard of care biomarkers following SGLT2 inhibition and changes in markers of cardiac remodeling as identified on echocardiography. Further exploratory analysis will seek to correlate changes in quantitative and qualitative heart failure outcomes with changes in both novel and standard of care cardiac biomarkers.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '40 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients identified with heart failure (both reduced ejection fraction and preserved) who are on optimal standard therapy and are candidates for treatment with SGLT2 inhibition will be identified from local heart failure databases, and local heart failure clinics. Following signed, informed consent and screening, patients will be enrolled into the trial.', 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Provision of signed informed consent prior to any study specific procedures.\n2. Male or female, between 40 and 90 years of age.\n3. LVEF \\<50% on echocardiography or if \\>50%, co-existing structural markers of diastolic dysfunction must be present;\n\n * LA width (diameter) ≥3.8 cm or LA length ≥5.0 cm, or LA area ≥20 cm, or LA volume ≥55 mL or LA volume index ≥29 mL/m.\n * Left ventricular hypertrophy.\n * Markers of diastolic dysfunction as assessed by pulsed wave doppler echocardiography.\n * N-terminal pro-B-type natriuretic peptide (NT-proBNP) of at least 125pg per millilitre (or ≥365pg per millilitre if co-existing atrial fibrillation).\n4. New York Heart Association (NYHA) class II, III, or IV symptoms.\n5. On optimal tolerated evidence-based HF medications.\n6. Patients may be ambulatory or recently hospitalized; however, must be \\>6 weeks post-discharge on stable diuretic therapy.\n\nExclusion Criteria:\n\n1. Receiving therapy with an SGLT2 inhibitor \\> 6 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor.\n2. Severe (eGFR \\<20 mL/min/1.73m2), unstable or rapidly progressing renal disease at the time of recruitment.\n3. Type 1 diabetes mellitus\n4. Recent hospitalisation \\< 1 month.\n5. Symptomatic hypotension or systolic BP \\<95 mmHg at 2 out of 3 measurements\n6. Symptomatic bradycardia or second or third-degree heart block without a pacemaker.\n7. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after recruitment.\n8. Cardiomyopathy secondary to uncorrected primary valvular disease, infiltrative, arrhythmogenic or right ventricular dysplasia.\n9. Significant comorbidity including; pulmonary lung disease requiring home oxygen or non-invasive ventilation, CTEPH or primary pulmonary hypertension.'}, 'identificationModule': {'nctId': 'NCT06140251', 'acronym': 'SiN-HF', 'briefTitle': 'Investigation of Biomarker Response to SGLT2 Inhibition in Heart Failure', 'organization': {'class': 'OTHER', 'fullName': "Queen's University, Belfast"}, 'officialTitle': 'Investigation of Biomarker Response to SGLT2 Inhibition Across Various Phenotypes of Heart Failure', 'orgStudyIdInfo': {'id': '22063CW-UC'}}, 'armsInterventionsModule': {'interventions': [{'name': 'Sodium-glucose cotransporter 2 inhibitor', 'type': 'DRUG', 'otherNames': ['SGLT2 inhibitors'], 'description': 'Patients identified with heart failure (both reduced ejection fraction and preserved) who are on optimal standard therapy and are candidates for treatment with SGLT2 inhibition will be identified from local heart failure databases, and local heart failure clinics. Following signed, informed consent and screening, patients will be allocated a first appointment where baseline clinical assessment and biomarker analysis will be obtained along with commencement on a SGLT2 inhibitor. Repeat assessment will be performed following a minimum period of 26 weeks.'}]}, 'contactsLocationsModule': {'locations': [{'city': 'Belfast', 'status': 'RECRUITING', 'country': 'United Kingdom', 'contacts': [{'name': 'Patrick Savage, MB BCH BAO Bsc (Hons)', 'role': 'CONTACT'}], 'facility': 'Belfast Health and Social Care Trust', 'geoPoint': {'lat': 54.59682, 'lon': -5.92541}}], 'centralContacts': [{'name': 'Patrick Savage, MB BChBAO Bsc', 'role': 'CONTACT', 'email': 'patrick.savage@belfasttrust.hscni.net', 'phone': '02890856665'}, {'name': 'Chris Watson, PhD', 'role': 'CONTACT', 'email': 'chris.watson@qub.ac.uk'}], 'overallOfficials': [{'name': 'Chris Watson, PHD', 'role': 'STUDY_CHAIR', 'affiliation': 'Queens University Belfast'}, {'name': 'Lana Dixon, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Belfast Health and Social Care Trust'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Queen's University, Belfast", 'class': 'OTHER'}, 'collaborators': [{'name': 'Belfast Health and Social Care Trust', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Dr', 'investigatorFullName': 'Chris Watson', 'investigatorAffiliation': "Queen's University, Belfast"}}}}