Impact of Elexacaftor-Tezacaftor-Ivacaftor Treatment on Metabolic, Epigenetic and Fecal Microbiota Profiles in People With Cystic Fibrosis.

NCT07363304 | Recruiting FDA Drug

• 1 other identifier: MEM-ETI
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 6

Brief Summary

Cystic Fibrosis (CF) is a genetic disease that affects multiple organs and systems. In recent years, the marketing of CFTR protein modulator drugs, such as the Elexacaftor-Tezacaftor-Ivacaftor (ETI) combination, has significantly improved patients' quality of life and prognosis. ETI, currently prescribed in Italy for CF patients over six years of age with at least one F508del mutation, has shown improvements in lung function, nutritional status, and a reduction in pulmonary exacerbations. In the coming months, ETI will be prescribable for patients aged $\\ge$ 2 years with at least one F508del mutation; furthermore, the EMA recently approved its use in all patients aged $\\ge$ 2 years, including those with mutations other than F508del (excluding patients with homozygous Class I mutations).Recent studies also highlight an impact on systemic metabolism, with an increase in blood cholesterol levels, blood pressure, and nutritional status, leading to a marked increase in patients with obesity. This could result in an increased long-term cardiovascular risk, especially in children with CF. Additionally, early data show that ETI also induces changes in the gut microbiota and epigenetic modifications by altering DNA methylation, particularly in genes crucial for the onset of CF-related complications, such as diabetes.The gut microbiota of CF patients differs from that of healthy controls, and ETI appears to improve microbial diversity while reducing intestinal inflammation and antibiotic resistance genes. Although ETI-related adverse events are mostly mild and similar to typical respiratory exacerbation symptoms (cough, headache, pharyngodynia, or transient bronchospasm), concerning side effects such as neuropsychiatric effects, intracranial hypertension, or liver failure have also been reported. Currently, it is not possible to predict which patients are at a higher risk of adverse events, but it is known that some of these are related to the blood levels of ETI's individual components. Therefore, monitoring these levels could be useful for dose optimization and reducing the risk of adverse events.Despite the publication of numerous real-world studies on the efficacy and safety of ETI and the sharing of recent standards of care for CF patients on modulator therapy, prospective studies are desirable, especially in the pediatric population. These are needed to monitor metabolic and epigenetic parameters, as well as changes in the fecal microbiota, correlating them with the blood levels of individual ETI components.

Conditions

Cystic Fibrosis (CF)

Outcome Measures

Primary Outcomes (1)

• Difference in DNA methylation level before and after the start of therapy

  baseline, 3, 6, 9, 12, 24 months post-Elexacaftor, Tezacaftor, Ivacaftor

Secondary Outcomes (2)

• Difference in serum levels of fatty acids, amino acids, sugars and cytokines.

  baseline, 3, 6, 9, 12, 24 months post-Elexacaftor, Tezacaftor, Ivacaftor

• Correlation between serum levels of fatty acids, amino acids, sugars and cytokines and plasma levels of individual components of the triple modulator therapy (Elexacaftor, Tezacaftor, Ivacaftor)

  baseline, 3, 6, 9, 12, 24 months post-Elexacaftor, Tezacaftor, Ivacaftor

Interventions

Elexacaftor, Tezacaftor, Ivacaftor DRUG

Patients with CF, of any age, about to start Elexacaftor, Tezacaftor, Ivacaftor therapy

Also known as: Trikafta, Kaftrio

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will enroll patients with CF pre and post ETI therapy, followed up at included Italian CF centers.

You may qualify if:

• Patients with CF, of any age, about to start ETI therapy, in accordance with marketing authorization Italian legislative directives, followed at the participating CF centers.
• Obtaining informed consent.

You may not qualify if:

• CF patients not in ETI therapy and CF patients already in ETI therapy.

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (6)

Centro per la Fibrosi Cistica, Azienda Universitaria Ospedaliera Consorziale Policlinico

Bari, Bari, Italy

NOT YET RECRUITING

Dipartimento di Pediatria, Centro Fibrosi Cistica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Milano, Italy

NOT YET RECRUITING

Unità Pediatrica, Dipartimento di Scienze Mediche Traslazionali, Centro di Riferimento Regionale per la Fibrosi Cistica, Università degli Studi di Napoli Federico II

Naples, Napoli, Italy

NOT YET RECRUITING

Ospedale pediatrico Bambino Gesù, IRCCS, Dipartimento Pediatrico Universitario Ospedaliero, UOC Pneumologia e Fibrosi Cistica

Roma, Roma, Italy

NOT YET RECRUITING

Centro per la Fibrosi Cistica, Ospedale Infantile Regina Margherita

Torino, Torino, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Meyer Istituto di Ricovero e Cura a Carattere Scientifico

Florence, 5016, Italy

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

elexacaftor, ivacaftor, tezacaftor drug combination

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Central Study Contacts

Vito Terlizzi, Medical Doctor

CONTACT

+39 055 566 2474; vito.terlizzi@meyer.it

Cristina Fevola, Ph.D.

CONTACT

+39 055 566 2780; cristina.fevola@meyer.it

Study Design

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

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: January 23, 2026
• Study Start: December 2, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: January 26, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)