Impact of Highly Effective Modulator Therapy on the Cystic Fibrosis Microbiome

NCT05982795 | Recruiting

• 1 other identifier: STUDY02001953
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• Difference in nasal bacterial community composition between CFTR-MT cohort and Non-CFTR-MT cohort

  Difference in microbial communities in mucus swabs between cystic fibrosis patients on CFTR-MT and cystic fibrosis patients not on CFTR-MT.

  Baseline, 6 months, 12 months, 18 months, 24 months

• Difference in inflammatory profiles between CFTR-MT cohort and Non-CFTR-MT cohort

  Difference in microbiome swab cytokine assay results between cystic fibrosis patients on CFTR-MT and cystic fibrosis patients not of CFTR-MT.

  Baseline, 6 months, 12 months, 18 months, 24 months

Secondary Outcomes (6)

• Difference in Sniffin' Sticks test scores between the CFTR-MT cohort and Non-CFTR-MT cohort

  Baseline, 6 months, 12 months, 18 months, 24 months

• Difference in the University of Pennsylvania Smell Identification Test scores between the CFTR-MT cohort and Non-CFTR-MT cohort

  Baseline, 6 months, 12 months, 18 months, 24 months

• Difference in Cystic Fibrosis Questionnaire-Revised survey responses between CFTR-MT cohort and Non-CFTR-MT cohort

  Baseline, 6 months, 12 months, 18 months, 24 months

• Difference in Sino-nasal Outcome Test-22 (SNOT-22) survey scores between CFTR-MT cohort and Non-CFTR-MT cohort

  Baseline, 6 months, 12 months, 18 months, 24 months

• Difference in Sinus Control Test survey scores between CFTR-MT cohort and Non-CFTR-MT cohort

  Baseline, 6 months, 12 months, 18 months, 24 months

Study Arms (2)

CFTR-MT Group

The cohort of adult cystic fibrosis patients that are currently on Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy (CFTR-MT) will be asked to complete the following research activities at baseline and every six months following for a two-year period. 1. Nasal endoscopy with microbiome swab and mucus collection through filter paper and sponge 2. The Sniffin' Sticks extended test kit and/or the University of Pennsylvania Smell Identification Test (UPSIT) 3. 4 validated quality of life questionnaires: 1. Cystic Fibrosis Questionnaire Revised (CFQ-R) 2. Sino-Nasal Outcome Test-22 (SNOT-22) 3. Sinus Control Test (SCT) 4. Questionnaire of Olfactory Disorders

Other: Nasal endoscopy with microbiome swab and mucus collection through filter paper and sponge; Other: Olfactory Function Testing; Other: Survey Completion

Non-CFTR-MT Group

The cohort of adult cystic fibrosis patients that are not currently on Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy (CFTR-MT) will be asked to complete the following research activities at baseline and every six months following for a two-year period. 1. Nasal endoscopy with microbiome swab and mucus collection through filter paper and sponge 2. The Sniffin' Sticks extended test kit and/or the University of Pennsylvania Smell Identification Test (UPSIT) 3. 4 validated quality of life questionnaires: 1. Cystic Fibrosis Questionnaire Revised (CFQ-R) 2. Sino-Nasal Outcome Test-22 (SNOT-22) 3. Sinus Control Test (SCT) 4. Questionnaire of Olfactory Disorders

Other: Nasal endoscopy with microbiome swab and mucus collection through filter paper and sponge; Other: Olfactory Function Testing; Other: Survey Completion

Interventions

Survey Completion OTHER

Participants will be asked to complete the validated Cystic Fibrosis Questionnaire-Revised (CFQ-R) survey. This survey evaluates Cystic Fibrosis-specific and general quality of life metrics. Participants will also be asked to complete the validated Sino-nasal Outcome Test-22 (SNOT-22) which is the most commonly used survey for evaluating outcomes in patients with chronic rhinosinusitis. Participants will also be asked to complete the validated Sinus Control Test (SCT) - a 4-question questionnaire that assesses disease control in chronic rhinosinusitis. Participants will be asked to complete the questionnaire of olfactory disorders (QOD). This is a 25-question validated survey used to assess the impact of olfactory dysfunction on patients with sinonasal disease.

CFTR-MT Group; Non-CFTR-MT Group

Nasal endoscopy with microbiome swab and mucus collection through filter paper and sponge OTHER

A CultureSwab MaxV(+) (BD, Franklin Lakes, NJ) will be placed under endoscopic visualization to the middle meatus through a sterile sheath (red rubber urinary catheter) and gently rotated 5 full turns or until the tip is saturated with mucus (no more than 20 seconds). Under direct visualization, a sterile Leukosorb sponge (Leukosorb; Pall Scientific, Port Washington, NY) will be placed in the middle meatus. A piece of Leukosorb filter paper will additionally be placed in the olfactory cleft. The sponge and paper will be left for 5 minutes and will then be removed under direct visualization and collected for analysis.

CFTR-MT Group; Non-CFTR-MT Group

Olfactory Function Testing OTHER

Olfactory function will be tested using the Sniffin' Sticks extended test kit (MediSense, NL) using the established threshold, discrimination, and identification (TDI) scoring system. Odors will be delivered using felt-tip pens (Sniffin' Sticks, MediSense, NL). The pen cap will be removed from the pen for approximately 3 seconds, and the pen's tip will be brought in front of the subject's nose and carefully moved from left to right nostril. Threshold testing will be obtained by asking the subject to identify the pen containing the odor from two pens containing only solvent. This will be conducted starting with the lowest concentration of odor and moving stepwise until patient is no longer able to identify the odor from the solvent. Subjects may also be asked to complete the University of Pennsylvania Smell Identification Test (UPSIT). The UPSIT can be self-administered and uses microencapsulated odorants which are released by scratching standardized odor-impregnated test booklets.

CFTR-MT Group; Non-CFTR-MT Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

The biospecimens collected during this study will be endoscopically directed nasal samples from the middle meatus and olfactory cleft.

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

• Ryan E Little, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan E Little, MD

CONTACT

(603) 650 8123; Ryan.E.Little@hitchcock.org

Michaela M Geffert, BS

CONTACT

michaela.m.geffert@hitchcock.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery, Geisel School of Medicine

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 9, 2023
• Study Start: November 8, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

US (1)