Fibroblast Growth Factor 23 and Risk of Cardiac Arrhythmias in Hemodialysis Patients (FibCA-HD)

July 31, 2025 updated by: Antonio Bellasi

Fibroblast Growth Factor 23 and Risk of Cardiac Arrhythmias in Hemodialysis Patients: a Proof-of-concept Study (FibCa-HD)

Despite recent progress in the field of hemodialysis (HD), mortality remains unacceptably high, particularly due to cardiac arrhythmias. Recent evidence suggests that fibroblast growth factor 23 (FGF23) is implicated in the pathogenesis of cardiac arrhythmias and sudden death. However, several aspects of both the pathogenetic mechanism(s) as well as the actual association in individuals with Chronic Kidney Disease (CKD) and the effect of dialysis clearance of FGF23 need to be elucidated.

The investigators aim at testing the independent association of FGF23 changes due to dialysis removal and electrocardiographic (ECG) abnormalities (namely QTc prolongation) in a well characterized sample of patients undergoing maintenance HD. The study will be developed in the Division of Nephrology, Ente Ospedaliero Cantonale.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This is an exploratory, observational, prospective, mono-center study that aims to elucidate the pathogenesis of cardiac repolarization and arrhythmias in subjects with CKD receiving maintenance dialysis.

This exploratory research project aims to confirm the link between FGF23 and ECG abnormalities (QTc as a proxy for cardiac arrhythmias) in a well-characterized sample of HD patients and expand our understanding of the molecular mechanisms by which FGF23 may trigger arrhythmias.

Previous works suggest that FGF23 cardiac toxicity may be mediated by the activation of FGFR4 and that modulation of FGF23-FGFR4 signaling through monoclonal antibodies can attenuate the toxic effects of FGF23 on the CM. Although these preliminary data warrant clinical and molecular confirmation, they also suggest FGF23-FGFR4 modulation as a novel potential therapeutic target in CKD to improve morbidity and mortality.

During a standard dialysis session, FGF23 is acutely removed while Ca2+ is provided to the patients. However, shortly after the HD session completion, it was documented that FGF23 serum levels rebound. The investigators hypothesize that acute reduction and subsequent rebound of circulatory levels of FGF23 coupled with calcium loading induced by HD may favour a Ca 2+ influx in the CM and trigger cardiac arrhythmias.

This exploratory study aims to determine the independent association between variations in serum levels of FGF23 and QTc (msec) during and after dialysis. In particular, the primary endpoint of the study is defined as the association between QTc variations (msec) defined as the difference between QTc pre-dialysis and QTc 1 hour after dialysis session completion and variations of serum levels of FGF23 defined as the difference between serum levels of FGF23 at dialysis session completion and after 1-hour form dialysis session completion. The investigators hypothesize that these time points should maximize the chance of detecting a significant association between the exposure variable (FGF23) and the outcome of interest (QTc).

All study procedures are non-invasive, and they will be carried out between the beginning of the last HD of the week and the beginning of the first HD of the following week (long interdialytic interval) to allow for the maximum variation of serum levels of FGF23 between dialysis sessions.

All study-related procedures are performed on top of standard clinical practice, and guidelines are performed non-invasively. Study participants will undergo the following procedures:

  • ECG: A standard 12-leads ECG will be recorded at the beginning, at the end as well as 60 minutes after the end of the last HD session of the week and at the beginning of the first HD session of the following week. All readings will be performed will be centralized and read by a single investigator blinded to clinical information at EOC.
  • Laboratory assessment: a blood sample will be taken at the beginning, at the end, and 60 minutes after the end of the last HD session of the week and at the beginning of the first HD session of the following week. Laboratory investigations will check the serum values of cardiovascular biomarkers (including FGF23) associated with QTc and volume expansion (OH: overhydration). Venous blood samples for measurement of cardiovascular biomarkers will be drawn at each time point and stored in the biobank at Ente Ospedaliero Cantonale (EOC) according to the standard procedures. These aliquotes will be used to assess FGF23 and for subsequent in-vitro evaluation of the cardiac arrhythmogenicity of patients' sera in relation to the homeostasis variation induced by HD.
  • Volume assessment: total body weight will be measured at dialysis session, to calculate the net body weight increase during the long interval. Overhydration (OH) will be quantitatively assessed with a portable whole-body bioimpedance spectroscopy device (Fresenius Medical Care GmbH, Bad Homburg, Germany). The total body water (TBW), the extracellular water (ECW), the intracellular water (ICW), and the OH are calculated as previously defined
  • Applanation tonometry: Central blood pressure (BP) values and aortic pressure waveforms will be obtained non-invasively directly from the common carotid artery using a validated high fidelity PulsePen tonometer (DiaTecne, San Donato Milanese, Italy). In particular, the subendocardial viability ratio (SEVR) will be calculated during the first HD session of the week according to the central BP wave form as previously reported
  • Echocardiogram: If no echocardiogram exam within 12 months from study inception is available in the patient's chart, a two-dimensional echocardiographic study will be performed before the first HD session of the week utilizing a standard equipment as per standard clinical practice. Digital images will be acquired in the long axis and short axis parasternal views and the apical four and two chamber views and three-cycle clips will be stored on magnetic optical disks for future review. The presence of valvular calcification (aortic and mitral valve) as well as systolic and diastolic function assessment will be performed.

Adverse event: The occurrence of any adverse events (AE) will be recorded for the occurrence of any event from study inception until the end of the following week This exploratory study will be carried out at the Division of Nephrology, Ente Ospedaliero Cantonale (EOC), Ticino, Switzerland.

Study Type

Observational

Enrollment (Estimated)

30

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 Backup

Study Locations

  • Switzerland
      • Lugano, Switzerland, CH-6903
        • Recruiting
        • Servizio di Nefrologia, Ospedale Regionale di Lugano, Civico
        • Contact:
        • Principal Investigator:
          • antonio bellasi, MD, PhD
        • Sub-Investigator:
          • Davide Salera, MD

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult subjects on maintenance hemodialysis

Description

The study envisages the enrolment of:

  • Adult subjects (>18 years of age) who can sign an informed consent.
  • on maintenance HD (for at least 3 months)

Exclusion Criteria:

  • history of cardiac arrhythmias at study recruitment define as atrial fibrillation or pace-maker assisted cardiac rhythm

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

Cohorts and Interventions

Group / Cohort
Subjects on maintenance hemodialysis

The study envisages the enrolment of:

  • adult subjects (>18 years of age) who are able to sign an informed consent.
  • on maintenance HD (for at least 3 months)
  • without history of cardiac arrhythmias at study recruitment define as atrial fibrillation or pace-maker assisted cardiac rhythm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Associations of QTc and FGF23 changes
Time Frame: the primary endpoint will be assessed one hour after dialysis cessation
The primary endpoint of the study is defined as the association between QTc variations (msec) defined as a continuous variable as the difference between QTc pre-dialysis and QTc 1 hour after dialysis session completion and variations of serum levels of FGF23 defined as a continuous variable as the difference between serum levels of FGF23 at dialysis session completion and after 1-hour form dialysis session completion. We hypothesize that these time points should maximize the chance of detecting a significant association between the exposure variable (FGF23) and the outcome of interest (QTc).
the primary endpoint will be assessed one hour after dialysis cessation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To gauge the dynamic association between FGF23 and QTc we will also explore
Time Frame: these endpoints will be assessed between dialysis session initiation and 1 hour after dialysis session cessation
A. Association of serum levels of FGF23 and QTc (msec) at dialysis session initiation (both utilized as continuous variables) B. Association of serum levels of FGF23 and QTc (msec) at dialysis session completion C. Association of serum levels of FGF23 and QTc (msec) 1 hour after dialysis session completion D. Association of QTc variations (msec - defined as the difference between QTc pre-dialysis and QTc after dialysis session completion) and serum levels of FGF23 variations before and after dialysis session completion (defined as the difference between serum levels of FGF23 at dialysis session initiation and dialysis session completion) E. Association of QTc variations (msec - defined as the difference between QTc at dialysis session completion and QTc 1 hour after dialysis session completion) and serum levels of FGF23 variations before and 1 hour after dialysis session completion (defined as variable as the difference between serum levels of FGF23 at dialysis session completion)
these endpoints will be assessed between dialysis session initiation and 1 hour after dialysis session cessation
To gauge the dynamic association between FGF23 and QTc we will also explore
Time Frame: These endpoints will be assessed bewteen the beginning of the last dialysis of the week and the beginning of the first dialysis of the following week (72 hours)

A. Association of QTc variations (msec - defined as the difference between QTc at dialysis session completion and QTc 72 hours after dialysis session completion) and serum levels of FGF23 variations before and after 72 hours from dialysis session completion (defined as the difference between serum levels of FGF23 at dialysis session completion and 72 hours after dialysis session completion).

B. Association of serum levels of FGF23 and QTc (msec) at the beginning of the first dialysis of the week, after the long interdialytic interval.
These endpoints will be assessed bewteen the beginning of the last dialysis of the week and the beginning of the first dialysis of the following week (72 hours)

Collaborators and Investigators

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

Sponsor

Antonio Bellasi

Investigators

  • Principal Investigator: Antonio Bellasi, MD, PhD, Ente Ospedaliero Cantonale, Bellinzona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

October 12, 2024

Primary Completion (Estimated)

October 31, 2025

Study Completion (Estimated)

December 30, 2025

Study Registration Dates

First Submitted

October 30, 2024

First Submitted That Met QC Criteria

October 30, 2024

First Posted (Actual)

October 31, 2024

Study Record Updates

Last Update Posted (Actual)

August 5, 2025

Last Update Submitted That Met QC Criteria

July 31, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FibCA-HD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

IPD maybe shared upon request and in respect with the regulation on data protection

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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