Pulmonary Vascular Disease in CF

NCT04549077 | Active Not Recruiting

• 1 other identifier: 2019-1239
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 2

Brief Summary

In this project, the investigators seek to understand the role of endothelial cells in Cystic Fibrosis (CF) lung disease. This objective will be achieved by conducting a cross sectional clinical study to define the morphology of the pulmonary circulation across a range of lung function coupled with a mechanistic study of the effect of dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) in endothelial cells on vasculogenesis, epithelial morphogenesis and epithelial CFTR function. Toward that end, the investigators propose the following hypotheses; (a). Loss of pulmonary small blood vessels begins early in the CF lung and worsens with disease progression, (b).VEGFR2-CFTR interactions happen at the plasma membrane of endothelial cells and is likely to be involved in transendothelial ion transport (c) impaired VEGFR2-CFTR interactions on the endothelial cells will have a profound effect on vasculogenesis, epithelial morphogenesis and ion transport. The first hypotheses will be tested through this clinical study. The following 2 hypotheses will be tested through laboratory studies that do not involve human subjects.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Pulmonary Disease; Pediatric

Outcome Measures

Primary Outcomes (2)

• The ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).

  In Aim 1A, the reconstruction of pulmonary vasculature will be measured by the primary functional outcome variable, the ratio (BV5/TBV) of blood volume in small \< 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).

  At baseline

• The change in the the ratio (BV5/TBV) of blood volume in small < 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).

  In Aim 1A, the change in the reconstruction of pulmonary vasculature between the baseline and 6 month visit imaging will be measured by the primary functional outcome variable, the ratio (BV5/TBV) of blood volume in small \< 5mm2 blood vessels (BV5) to the total pulmonary blood volume (TBV).

  For a subset of 31 patients, the change in ratio will be measured between the baseline visit and 6 months post Trikafta therapy.

Secondary Outcomes (2)

• Forced Expiratory Volume as a percent of the referenced value (FEV1%)

  Baseline

• The change in Forced Expiratory Volume as a percent of the referenced value (FEV1%)

  For a subset of 31 patients, the change from baseline to 6 months post Trikafta therapy.

Study Arms (2)

Cystic Fibrosis Patients

Patients with Cystic Fibrosis.

Historical Controls

Patients diagnosed with solid tumors, who have had a normal chest CT scan during screening for possible metastasis

Eligibility Criteria

• Age: 5 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

93 subjects with cystic fibrosis, 5-21 years of age, equally divided between males and females will be recruited from 2 CF centers; Cincinnati Children's Hospital and Riley Children's Hospital.

You may qualify if:

• years of age
• diagnosis of CF based on a positive sweat test and genetic testing
• Baseline pulmonary condition defined as a) Absence of signs and symptoms of pulmonary exacerbation, b) Baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months, c) Patients should be off acute antibiotics for 2 weeks or longer.
• Subjects should be able to perform an acceptable and reproducible spirometry
• Study population will be equally divided between three groups based on FEV1%, (FEV1% ≥ 90); moderate (60 ≤ FEV1% \< 90)

You may not qualify if:

• Enrollment in clinical trials of CFTR correctors and or potentiator
• Enrollment in gene therapy trial
• Pregnancy.
• Historical Controls
• solid tumor diagnosis
• had chest CT scan to survey possible metastasis or any other lung disease
• age and gender matched to Cystic Fibrosis patients

Sponsors & Collaborators

• Cystic Fibrosis Foundation: collaborator
• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (2)

Riley Hospital for Children

Indianapolis, Indiana, 46204-3509, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3026, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis; Lung Diseases

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2020
• First Posted: September 16, 2020
• Study Start: July 29, 2020
• Primary Completion: November 14, 2024
• Study Completion: January 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)