Surfactant Derived Protocol in Heart Failure

NCT06896461 | Completed

• 1 other identifier: CCM470
• Study Type: interventional
• Target: 471
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary surfactant is a highly surface-active lipoprotein complex that lines the alveoli and terminal airways, reducing surface tension and preventing alveolar collapse at the end of expiration. It consists of a lipid (90%) and a protein fraction, with surfactant proteins SP-A, SP-B, SP-C, and SP-D playing crucial roles. SP-B is essential for surfactant function, and its absence leads to severe respiratory failure. Recent studies have shown that plasma SP-B levels are elevated in heart failure (HF) patients, likely due to increased pulmonary microvascular pressure and alveolar-capillary barrier dysfunction. SP-B correlates with HF severity and prognosis, outperforming functional parameters as a predictor of hospitalization. This study aims to compare surfactant proteins with other biomarkers, including RAGE, a receptor linked to lung injury. Using advanced multiplex mass spectrometry, the study seeks to validate immature SP-B as a reliable diagnostic and prognostic marker for HF.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Evaluation of lung surfactant protein type B levels in heart failure by multiplexing methodology

  analyses will be carried out using modern multiplexing methodology based on mass spectrometry, that will make it possible to validate the role of the immature SP-B protein as an accurate marker for the diagnosis and prognosis of heart failure

  2 years

Study Arms (1)

Heart failure patients

EXPERIMENTAL

All heart failure patients wll be charachterized according to cardiopulmonary exercise test variables, spirometry and biomarkers collection

Diagnostic Test: Cardiopulmonary exercise test; Diagnostic Test: Lung function; Diagnostic Test: Biomarkers evaluation

Interventions

Cardiopulmonary exercise test DIAGNOSTIC_TEST

The test consists of physical exertion performed on a stationary bike with a progressively increasing workload, continuing until specific electrocardiographic and/or clinical criteria are met or muscle fatigue occurs. The rate of workload increase (ramp) will be personalized and adjusted to ensure the exercise reaches its peak in approximately 10 minutes. Throughout the test, a continuous electrocardiogram (ECG) will be recorded, and various physiological parameters will be measured. These include ventilation, oxygen consumption, carbon dioxide production, and related derived parameters, which will be assessed using a mouthpiece or a face mask through which you will need to breathe for the entire duration of the test. Blood pressure will also be measured at two-minute intervals.

Heart failure patients

Lung function DIAGNOSTIC_TEST

Assessment of both static lung volumes (vital capacity, total lung capacity, functional residual capacity, and residual volume) and dynamic lung volumes (forced vital capacity and forced expiratory volume in one second, or FEV1). Additionally, the flow-volume curve is measured, generated by continuously recording airflow and volume using an electronic spirometer during a foThe diffusion capacity for carbon monoxide (DLCO) can be measured using the single-breath method (DLCOSB). The patient inhales a small, known concentration of carbon monoxide (CO), holds their breath for 10 seconds, and then exhales. A sample of alveolar gas (from the end of expiration) is analyzed to determine the amount of CO absorbed during the breath, expressed in ml/min/mm Hg. By repeating the test with inhalation of gas mixtures containing different oxygen concentrations (approximately 20%, 40%, and 60%), it is possible to assess the diffusion subcomponents: the membrane component and capillary blood volume.

Heart failure patients

Biomarkers evaluation DIAGNOSTIC_TEST

Samples of plasma will be collected for bimarkers quantification in heart failure. Speecifically, plasma levels will be quantitatively assessed using plasma obtained from venous blood. Blood will be collected in tubes containing 0.129 M Na-citrate (9 volumes of blood to 1 volume of Na-citrate), immediately centrifuged at 3000 g for 15 minutes at 4°C. Circulating levels of both immature and mature SP-B will be analyzed via Tricine gel electrophoresis followed by immunoblotting with an anti-SP-B antibody, allowing for the detection of all SP-B isoforms (proprotein 42 kDa, intermediate 23 kDa, and mature 8 kDa). To validate potential heart failure biomarkers, a quantitative, scalable, and cost-effective method-Multiple Reaction Monitoring (MRM)-will be used. MRM, based on triple quadrupole mass spectrometry, enables precise quantification of proteins/peptides and their isoforms in complex biological samples.

Heart failure patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart failure diagnosis
• Left ventricular ejection fraction \<40%
• Stable clinical condition

You may not qualify if:

• Relevant comorbidities
• usual contraindications to cardiopulmonary testing.

Sponsors & Collaborators

• Centro Cardiologico Monzino: lead
• Ospedale San Luca, Istituto Auxologico Italiano, Milano: collaborator

Study Sites (1)

Centro Cardiologico Monzino

Milan, Italy, 20138, Italy

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Exercise Test; Respiration

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 26, 2025
• Study Start: May 6, 2016
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

IT (1)