RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-05-01

Study Completion:2027-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04580368

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:6 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

John Brewington, MD

CONTACT

513-736-0614

John.Brewington@cchmc.org

Rory OShaughnessy, MPH

CONTACT

513-803-0024

Rory.OShaughnessy@cchmc.org

Study Locations (Sites)

CCHMC

Cincinnati, Ohio, 45203

United States

Collaborators and Investigators

Sponsor: Children's Hospital Medical Center, Cincinnati

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-01

Study Completion Date2027-01-31

Study Record Updates

Study Start Date2021-05-01

Study Completion Date2027-01-31

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Cystic Fibrosis