Investigation of Biomarker Response to SGLT2 Inhibition in Heart Failure (SiN-HF)

November 15, 2023 updated by: Chris Watson, Queen's University, Belfast

Investigation of Biomarker Response to SGLT2 Inhibition Across Various Phenotypes of Heart Failure

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • Belfast, United Kingdom
        • Recruiting
        • Belfast Health And Social Care Trust
        • Contact:
          • Patrick Savage, MB BCH BAO Bsc (Hons)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

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.

Description

Inclusion Criteria:

  1. Provision of signed informed consent prior to any study specific procedures.
  2. Male or female, between 40 and 90 years of age.

  3. 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).
  4. New York Heart Association (NYHA) class II, III, or IV symptoms.
  5. On optimal tolerated evidence-based HF medications.
  6. Patients may be ambulatory or recently hospitalized; however, must be >6 weeks post-discharge on stable diuretic therapy.

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To evaluate whether SGLT2 inhibition in heart failure produces changes in novel cardiac biomarkers.
Time Frame: 26 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography.
Time Frame: 26 weeks
Changes in global longitudinal strain (GLS) (%) and left ventricular systolic function [LVEF (%)] as assessed on strain echocardiography.
26 weeks
To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by echocardiography.
Time Frame: 26 weeks
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)].
26 weeks
To evaluate if SGLT2 inhibition produces changes in markers of cardiac remodeling as assessed by diastolic parameters on echocardiography.
Time Frame: 26 weeks
Change in left ventricular lateral e' (cm/s), septal e' (cm/s) and E/e' ratio obtained from echocardiography.
26 weeks
To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.
Time Frame: 26 weeks
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)].
26 weeks
To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.
Time Frame: 26 weeks
Changes in standard care biomarker of inflammation following SGLT2 inhibition by measurement of serum C-reactive protein [CRP (mg/dL).
26 weeks
To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.
Time Frame: 26 weeks
Changes in standard care cardiac of diabetic biomarkers following SGLT2 inhibition using measurement of glycosylated haemoglobin [HbA1c (mmol/mol)].
26 weeks
To evaluate changes in quantitative markers of heart failure outcomes following initiation of SGLT2 inhibition in heart failure.
Time Frame: 26 weeks
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)].
26 weeks
To evaluate changes in qualitative markers of heart failure outcomes.
Time Frame: 26 weeks.
Change in New York Heart Association (NYHA) score, classified on a scale I to IV, with a higher number indicating a worse outcome.
26 weeks.
To evaluate changes in qualitative markers of heart failure outcomes.
Time Frame: 26 weeks.
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.
26 weeks.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling.
Time Frame: 26 weeks.
Correlation of log transformed delta change in novel cardiac biomarkers with global longitudinal strain [GLS (%)] and left ventricular ejection fraction [LVEF (%)].
26 weeks.
Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with markers of cardiac remodeling.
Time Frame: 26 weeks.
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)].
26 weeks.
Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with qualitive markers of heart failure outcomes.
Time Frame: 26 weeks.
Correlation of log transformed delta change in novel cardiac biomarkers with change in Kansas-City Cardiomyopathy Questionnaire (KCCQ).
26 weeks.
Exploratory evaluation of correlation of effect of SGLT2 inhibition on novel cardiac biomarkers with qualitive markers of heart failure outcomes.
Time Frame: 26 weeks.
Correlation of log transformed delta change in novel cardiac biomarkers with change in Change in New York Heart Association (NYHA) score.
26 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Queen's University, Belfast

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Belfast Health and Social Care Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Chris Watson, PHD, Queens University Belfast
  • Principal Investigator: Lana Dixon, MD, Belfast Health And Social Care Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 21, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 18, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 18, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 22063CW-UC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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