Clinical trial NCT05982795: Impact of Highly Effective Modulator Therapy on the Cystic Fibrosis Microbiome
Official title: Impact of Highly Effective Modulator Therapy on Sinonasal Microbial Communities, Host Mucosal Inflammatory Environment and Quality of Life in Adults with Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2023-08-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population is adult, English-speaking cystic fibrosis patients being seen at the New Hampshire Cystic Fibrosis Center.

Brief summary: The goal of this observational study is to learn about the effects of a specific cystic fibrosis therapy (Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy) on chronic sinonasal disease. The main questions it aims to answer are:

1. How does this therapy impact bacterial communities in the paranasal sinuses?
2. How does this therapy impact inflammation in the paranasal sinuses and olfactory cleft?
3. How does this therapy impact sense of smell and sinonasal disease burden in individuals with cystic fibrosis?
4. How does this therapy impact disease-specific and general quality of life of individuals with cystic fibrosis?

Participants will be asked to provide samples from their nose, complete testing of their sense of smell, and complete surveys about their quality of life and sense of smell in this study.

Researchers will compare study results between patients who are currently undergoing Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy and patients who are not currently undergoing therapy.

Detailed description: The goal of this study is to characterize the effects of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy on the sinonasal microbial communities and inflammatory profiles in adults with cystic fibrosis. Participants will be asked to complete the below research activities on a 6-month basis over the course of two years to total 5 research visits (0 months, 6 months, 12 months, 18 months, 24 months).

A mucus sample from the middle meatus will be obtained and stored at 4ºC until culture analysis. Semi-quantitative bacterial cultures will be performed. Bacterial community composition will be quantified using 16S rRNA variable region (V4) amplicon sequencing and qPCR. Data preprocessing and taxonomic assignment will be performed using QIIME 2 (v 2023.2) and the SILVA 138.1 rRNA database. Abundance data will be further processed in R (v 4.3.0) using packages decontam, phyloseq, and vegan.

Samples from the middle meatus and olfactory cleft will be analyzed to investigate the inflammatory profiles of patients with cystic fibrosis. Both samples will be centrifuged at 4°C, 10,000 rpm for 10 minutes to extract the entire sample from the material. Samples will be transferred by pipette to cryovials, flash-frozen in liquid nitrogen, and stored in a -80°C environment until time of laboratory assay. The study will assess changes in immune status through cytokine arrays. To assess innate immune responses, a Bioplex Pro Human Inflammation Assay for 37 human cytokines (BD Biosciences) will be employed.

The study will also investigate if alterations in nasal microbiome and inflammatory profile correlate with changes in cystic fibrosis-specific quality of life (QOL) and olfaction outcomes. Participants will be asked to complete olfactory function testing using the Sniffin' Sticks extended test kit (MediSense, NL) and/or the University of Pennsylvania Smell Identification Test (UPSIT). Additionally, participants will be asked to complete the four following surveys to assess their quality of life as it relates to sinus symptom severity, disease control, and sense of smell: Cystic Fibrosis Questionnaire-Revised, Sino-nasal Outcome Test-22, Sinus Control Test, and Questionnaire of Olfactory Disorders.

Eligibility criteria: Inclusion Criteria:

* Subjects between the ages of 18 years old (inclusive) and 99 years old (inclusive)
* English-speaking
* Diagnosed with CF as established by genetic testing combined with clinical assessment and/or sweat chloride
* Patients being seen at the New Hampshire Cystic Fibrosis Center
* Adults able to sign informed consent

Exclusion Criteria:

* Adults unable to consent
* Individuals who are not yet adults
* Prisoners

Primary outcomes:
measure: Difference in nasal bacterial community composition between CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
measure: Difference in inflammatory profiles between CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
Secondary outcomes:
measure: Difference in Sniffin' Sticks test scores between the CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
measure: Difference in the University of Pennsylvania Smell Identification Test scores between the CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
measure: Difference in Cystic Fibrosis Questionnaire-Revised survey responses between CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
measure: Difference in Sino-nasal Outcome Test-22 (SNOT-22) survey scores between CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
measure: Difference in Sinus Control Test survey scores between CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
measure: Difference in Questionnaire of Olfactory Disorder survey scores between CFTR-MT cohort and Non-CFTR-MT cohort
timeFrame: Baseline, 6 months, 12 months, 18 months, 24 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Ryan E Little, MD
role: PRINCIPAL_INVESTIGATOR
References: