Investigation of Biomarker Response to SGLT2 Inhibition in Heart Failure

NCT06140251 | Unknown FDA Drug

• 1 other identifier: 22063CW-UC
• Study Type: observational
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure

Keywords

Heart failure; Cardiac imaging; SGLT2; Biomarkers

Outcome Measures

Primary Outcomes (1)

• To evaluate whether SGLT2 inhibition in heart failure produces changes in novel cardiac biomarkers.

  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.

  26 weeks

Secondary Outcomes (9)

• To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography.

  26 weeks

• To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography.

  26 weeks

• To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by diastolic parameters on echocardiography.

  26 weeks

• To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.

  26 weeks

• To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.

  26 weeks

Other Outcomes (4)

• Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling.

  26 weeks.

• Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling.

  26 weeks.

• Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with qualitive markers of heart failure outcomes.

  26 weeks.

Interventions

Sodium-glucose cotransporter 2 inhibitor DRUG

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.

Also known as: SGLT2 inhibitors

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Provision of signed informed consent prior to any study specific procedures.
• Male or female, between 40 and 90 years of age.
• LVEF \<50% on echocardiography or if \>50%, co-existing structural markers of diastolic dysfunction must be present;
• 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.
• Left ventricular hypertrophy.
• Markers of diastolic dysfunction as assessed by pulsed wave doppler echocardiography.
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) of at least 125pg per millilitre (or ≥365pg per millilitre if co-existing atrial fibrillation).
• New York Heart Association (NYHA) class II, III, or IV symptoms.
• On optimal tolerated evidence-based HF medications.
• Patients may be ambulatory or recently hospitalized; however, must be \>6 weeks post-discharge on stable diuretic therapy.

You may not qualify if:

• Receiving therapy with an SGLT2 inhibitor \> 6 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor.
• Severe (eGFR \<20 mL/min/1.73m2), unstable or rapidly progressing renal disease at the time of recruitment.
• Type 1 diabetes mellitus
• Recent hospitalisation \< 1 month.
• Symptomatic hypotension or systolic BP \<95 mmHg at 2 out of 3 measurements
• Symptomatic bradycardia or second or third-degree heart block without a pacemaker.
• Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after recruitment.
• Cardiomyopathy secondary to uncorrected primary valvular disease, infiltrative, arrhythmogenic or right ventricular dysplasia.
• Significant comorbidity including; pulmonary lung disease requiring home oxygen or non-invasive ventilation, CTEPH or primary pulmonary hypertension.

Sponsors & Collaborators

• Queen's University, Belfast: lead
• Belfast Health and Social Care Trust: collaborator

Study Sites (1)

Belfast Health and Social Care Trust

Belfast, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Heart Failure

Interventions

Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Chris Watson, PHD

  Queens University Belfast

  STUDY CHAIR

• Lana Dixon, MD

  Belfast Health and Social Care Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Savage, MB BChBAO Bsc

CONTACT

02890856665; patrick.savage@belfasttrust.hscni.net

Chris Watson, PhD

CONTACT

chris.watson@qub.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: November 5, 2023
• First Posted: November 18, 2023
• Study Start: August 21, 2023
• Primary Completion: September 1, 2024
• Study Completion: May 1, 2025
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

GB (1)