Recruiting

Cystic FibrosisTesting Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials

Sponsor:

Children's Hospital Medical Center, Cincinnati

Code:

NCT04580368

Conditions

Cystic Fibrosis

Eligibility Criteria

Sex: All

Age: 6+

Healthy Volunteers: Not accepted

Interventions

CFTR Modulators

Study Details

Brief summary:

The purpose of this study is to validate and utilize a personalized medicine approach to identify potential treatments with current FDA approved CFTR modifiers for non-approved CF gene mutations. The study will perform ex vivo testing of CFTR function and current marketed CFTR modulating drugs on expanded nasal cells at Cincinnati Children's Human Nasal Epithelium (HNE) Core Laboratory. The results will be confirmed and translated into bedside care through an N of 1 trial to determine effectiveness of treatment.

Conditions

Cystic Fibrosis

Study ID

NCT04580368

Start date

May 1, 2021

Status verified date

Jan, 2026

Completion date

Jan 31, 2030

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 6+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Signed informed consent (and assent when applicable)
Willing and able to adhere to the study visit schedule and protocol requirements
Male or Female ≥6 years old and within the FDA-approved range for the proposed modulator drug

Ivacaftor: ≥4 months old
Lumacaftor/Ivacaftor: 2 years old
Tezacaftor/Ivacaftor: 12 years old
Elexacaftor/Tezacaftor/Ivacaftor: ≥12 years old
At least one rare CFTR variant (incidence of <5% of the CF population)
Documentation of a CF diagnosis as evidenced by one or more clinical features of CF plus at least one of the following:

Sweat Chloride ≥60mmol/L by quantitative pilocarpine iontophoresis
Two mutations in the CFTR gene
Abnormal nasal potential difference (NPD) testing supportive of a CF diagnosis
FEV1 > 50% predicted for age
Stable chronic CF therapies with no changes in >28 days (except for chronic cycled inhaled antibiotics such as tobramycin)
Prescribed CFTR modulator by a licensed physician
No contraindication to treatment with the selected drug at the time of treatment initiation

Exclusion Criteria:

Presence of any condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient and/or quality of the data
For women of child bearing potential:

Positive pregnancy test or known pregnancy at Visit 1
Lactating
Unwilling to practice a medically acceptable form of contraception (acceptable forms include abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal during the study
BMI < 10th percentile for age (if <18 years old) or < 20kg/m2 (if ≥18 years old)
FEV1 ≤ 50% predicted for age
Growth of CF pathogens from sputum cultures that are associated with unstable disease (e.g., nontuberculous mycobacteria, Burkholderia spp) within six months of enrollment
Concomitant use of CYP3A inducers or inhibitors (e.g., voriconazole, fluconazole, rifampin) or prednisone (>20mg daily)
Concomitant conditions:

Poorly controlled diabetes mellitus (HbA1c >8.5 or glucosuria as noted below)
Advanced CF liver disease (cirrhosis with portal hypertension, ascites, or abnormal liver laboratory testing as noted below)
End stage renal disease
History of organ transplantation
Additional medical conditions that in the opinion of the Investigator place the patient at risk of participation or may impact the patient's ability to complete the trial (e.g., uncontrolled depression, anxiety disorder, poor adherence to CF therapies, active ABPA)
Any of the following abnormal laboratory values at the Screening Visit:

CBC
WBC >15,000 K/mcL or ANC <1,500 K/mcL
Hemoglobin <10 gm/dL
Platelets <50,000 K/mcL
Chemistries
>2+ Glucosuria
Clinically significant abnormalities as assessed by the Investigator
Glomerular filtration rate ≤50 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation)
Hepatic Function Testing / Coagulation Testing
≥3 × upper limit of normal (ULN) aspartate aminotransferase (AST)
≥3 × ULN alanine aminotransferase (ALT)
≥3 × ULN gamma-glutamyl transpeptidase
Total or direct bilirubin >2 × ULN
INR > 1.5 x ULN
Positive pregnancy test

Study Design

Enrollment

50 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: CFTR modulator or other therapies

CFTR modulator or active therapy

Interventions

CFTR Modulators

Participants with rare mutations will receive active therapy in N-of-1 design with participants serving as their own control

Primary outcome measure

ppFEV1 [ Time Frame: 16 weeks ]

Central Contacts and Locations

Central contacts

John Brewington, MD

513-736-0614 John.Brewington@cchmc.org

Rory OShaughnessy, MPH

513-803-0024 Rory.OShaughnessy@cchmc.org

Locations

CCHMC

Recruiting

Cincinnati, Ohio, United States, 45203

Contacts

John Brewington

5138031548 John.Brewington@cchmc.org

More Information

Sponsor

Children's Hospital Medical Center, Cincinnati

Last update posted

Jan 7, 2026

Last verified

Jan, 2026

Keywords

CFTR modulators
cystic fibrosis
HNE
human nasal epithelial cells
NPD
nasal potential difference
air-liquid interface
N-of-1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Children's Hospital Medical Center, Cincinnati on 2026-01-07.