Monitoring Response to Orkambi in Cystic Fibrosis Lung Disease by Inhaled Xenon MRI

NCT02848560 | Active Not Recruiting DMC

• 2 other identifiers: CINOO1-CF Orkambi and Xe MRI1R01HL131012-01A1
• Study Type: observational
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is an observational study for children with Cystic Fibrosis (CF) who are eligible based on their CF gene type. One group will be called the treatment group because they have the gene type (homozygous F508del) that makes them clinically eligible through their CF care provider to begin treatment with the new FDA approved CF drug called orkambi. For the control group, children will be enrolled who have a similar CF gene type (heterozygous F508del) but are not eligible to be prescribed orkambi. The two groups will be followed for four visits over about 3 to 4 years to observe changes in the lungs. Methods to measure the changes in lung disease will include: MRI with non-FDA approved inhaled xenon gas to take detailed images of the lungs, Pulmonary Function Tests (PFT), Lung Clearance Index (LCI), Baseline CT image of the lungs if not ordered as part of usual clinical care. The first two visits will be done before starting clinical treatment with orkambi and will be a minimum of 28 days apart and up to 18 months. The third visit will be scheduled about 3 months after starting orkambi and the fourth visit about 18 months later. For the control group, the timing of visits will be similar to treatment group and visits may be scheduled around annual CF care visits.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; orkambi; 129Xe MRI; hyperpolarized xenon; LCI; CFTR modulator therapy

Outcome Measures

Primary Outcomes (1)

• Hyperpolarized 129Xe MRI Image Analysis

  Lung defect calculations (total and lobar defect percentages) will be performed by evaluating the percentage of voxels with signals below a threshold value of 60% of the total lung mean signal.

  Visit 4 (year 3)

Study Arms (2)

Treatment

Observation of lung changes over time by hyperpolarized xenon MRI on CF patients homozygous for F508del CFTR mutation as they age into the FDA approved treatment window for the CFTR modulator orkambi. Subjects will be observed at 2 time points before starting clinically prescribed treatment (orkambi) and 2 time points while on orkambi.

Drug: Hyperpolarized Xenon

Control

Observation of lung changes over time by hyperpolarized xenon MRI on CF patients heterozygous for F508del CFTR mutation at similar timepoints to treatment group. Control subjects are not be eligible to be clinically prescribed orkambi based on FDA approval.

Drug: Hyperpolarized Xenon

Interventions

Hyperpolarized Xenon DRUG

Inhaled contrast for MRI occurring at each of 4 visits.

Also known as: 129Xe

Control; Treatment

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Cystic Fibrosis patients naïve to orkambi and with either homozygous F508del CFTR mutation or heterozygous F508del CFTR mutation and pancreatic insufficient.

You may qualify if:

• Treatment group:
• male or female between the ages of 6 through 12 years at enrollment
• two copies of the F508del CFTR mutation
• anticipated to be a candidate for treatment with orkambi
• Control group:
• male or female between the ages of 6 through 12 years at enrollment
• two non-functional CFTR mutations with one of them being F508del CFTR mutation
• not eligible for CFTR modulation therapy

You may not qualify if:

• FEV1 percent predicted of \<60%
• pregnancy

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

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

Study Officials

• Jason Woods, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: July 28, 2016
• Study Start: March 1, 2016
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)