Clinical Research Directory

TIDES 2.0: Prevalence and Longitudinal Course of Depression, Anxiety, and Behavior Problems in Children With Cystic Fibrosis Under 12 Years of Age

This is a longitudinal, observational epidemiological study designed to estimate the prevalence of depression, anxiety, and behavior problems in children ages 18 months through 11 years with cystic fibrosis (CF).

Phase 2 Study to Assess the Safety and Efficacy of ANG003

In this study, ANG003, a pancreatic enzyme replacement therapy (PERT; commonly called "enzymes"), is being investigated as a potential treatment for exocrine pancreatic insufficiency (EPI). People with EPI due to Cystic Fibrosis (CF) may be eligible to participate in this study. The primary objective of this study is to evaluate the safety of ANG003 and see if it works as well compared to Creon, an approved PERT.

Diagnostic Value of Oropharyngeal Suction and Effect of Respiratory Physiotherapy on the Detection of Microorganisms in the Pediatric Patient

The goal of this clinical trial is to determine the effectiveness of oropharyngeal suction in detecting microorganisms by comparing it with induced sputum and oropharyngeal swab samples. It also aims to assess the effect of respiratory physiotherapy on improving the results obtained in children aged 5-18 years with chronic lung disease. The main questions it aims to answer are: * What is the diagnostic efficacy of oropharyngeal suction in detecting microorganisms compared with induced sputum? * What is the effect of undergoing a physiotherapy session before sample collection? * How do the results obtained from oropharyngeal suction correlate with those obtained from oropharyngeal swabs? * How does the age of the participants affect the results obtained from each sampling technique and the effect of prior physiotherapy? * Are these techniques safe? Researchers will compare samples collected after a physiotherapy session with those collected without prior physiotherapy to determine whether physiotherapy improves culture results. Participants will be randomized into two groups: one group will undergo a physiotherapy session before sample collection, while the other will not. Three samples will be collected from each participant using oropharyngeal suction, an oropharyngeal swab, and induced sputum. Each participant may take part on multiple occasions, provided that at least one month has elapsed since their previous participation. On each occasion, participants will be randomized again.

PERCE-MUCO: Perceptions and Expectations of People With Cystic Fibrosis Regarding a Change in Treatment

PERCE-MUCO is a prospective, multicentre, mixed-methods observational study investigating the perceptions, expectations and treatment-change intentions of adults with cystic fibrosis who are currently treated with elexacaftor/tezacaftor/ivacaftor (ETI) or whose treatment has been medically discontinued. The study focuses on patients' stated willingness to switch from ETI to vanzacaftor/tezacaftor/deutivacaftor (VTD), and on the factors associated with this intention, including treatment satisfaction, knowledge and expectations regarding VTD, quality of life, treatment adherence, reported adverse effects, access-related concerns and desired support from an advanced practice nurse. The quantitative component uses a study-specific questionnaire and routine-care CFQ-R 14+ and Morisky-8 data. A qualitative component consists of semi-structured interviews at the Roscoff cystic fibrosis centre.

Assessment of Static and Dynamic Inspiratory Muscle Strength and Cardiorespiratory Fitness in Adults With Cystic Fibrosis

This study aims to examine and compare static and dynamic inspiratory muscle strength and cardiorespiratory fitness in adults with cystic fibrosis and their healthy peers.

OnTrackCF: Engagement, Feasibility, and Acceptability Study

This is a multi-site, nonrandomized study using mixed methods approach to evaluate the feasibility, acceptability, and user engagement of OnTrackCF for adults with Cystic Fibrosis (AWCF).

Type 2 Inflammation in Adults With Cystic Fibrosis

The goal of this observational study is to better understand why some adults with cystic fibrosis (CF) continue to have repeated pulmonary exacerbations, or episodes of worsening respiratory symptoms, despite treatment with highly effective CFTR modulator therapy. The study will focus on whether a type of inflammation called type 2 (T2) inflammation may contribute to these pulmonary exacerbations. The main questions this study aims to answer are: Are signs of T2 inflammation more common in adults with CF who have frequent pulmonary exacerbations? Are there differences in inflammation in the nose and airways between people who have frequent pulmonary exacerbations and those who do not? How do immune cells and inflammation change during a pulmonary exacerbation? Participants will: Allow researchers to collect information about their CF and pulmonary exacerbations from their medical records. Complete questionnaires about respiratory and sinus symptoms and quality of life. Provide research blood samples, samples from inside the nose, and exhaled breath condensate. Be followed for up to approximately 3 years, with additional research samples collected during qualifying pulmonary exacerbations when feasible. Participants will continue to receive their usual CF medical care. No experimental medications or treatments will be given as part of this study.

A Precision Medicine Approach to Assess Protein Function Loss and the Potential for CFTR Function Restoration in Cystic Fibrosis and Related Disorders

This multicenter translational research study integrates diagnostic analyses and ex-vivo functional testing to support future clinical trials evaluating the safety and efficacy of CFTR modulator treatments in individuals with cystic fibrosis (CF) carrying rare or orphan mutations that may benefit from these therapies. Patient-derived nasal epithelial cells will be collected through standardized nasal brushing procedures, expanded, and cultured under air-liquid interface conditions to generate differentiated epithelia. Short-circuit current measurements will be used to assess baseline CFTR dysfunction and evaluate functional recovery following treatment with available CFTR modulators. These results will be complemented by DNA sequencing to identify complex alleles, quantitative and qualitative CFTR mRNA analyses to investigate gene expression and splicing defects, and assessments of epithelial transcriptomics, surface liquid viscosity, and mucociliary transport to identify additional mechanisms contributing to CF-like lung disease. The study will not include patient follow-up. The duration of participation will be limited to the time required to perform and analyze the nasal brushing procedure. Baseline CFTR activity will be compared with previously published data from individuals without cystic fibrosis.

Feasibility and Acceptance of SonoHeal for Airway Clearance and Preliminary Comparison With the Standard of Care

The proposed study is to gauge the early feasibility and acceptance of the SonoHeal device. The study will evaluate the usability of the SonoHeal prototype using well-established Human Factors Engineering methods recommended by the FDA. The investigators will also obtain a preliminary comparison with the standard of care ACT device, High Frequency Chest Wall Oscillation (HFCWO).

SPutum Induction and Nebuliser deviCEs for Patients With CF

The goal of the SPICE-CF feasibility trial is to learn whether it is feasible to recruit and retain people with cystic fibrosis (CF) who are unable to produce sputum spontaneously in a study comparing two different nebuliser devices for sputum induction. The study will also assess how acceptable and practical the sputum induction procedures are. The main questions it aims to answer are: * Is it feasible to recruit and retain people with cystic fibrosis in a study comparing two nebuliser devices for sputum induction? * Can sputum be successfully obtained using each nebuliser device? * How acceptable are the two nebuliser devices to participants? * How long does sputum induction take with each device? * What microorganisms are identified in sputum collected using each device? * Can a visual scoring system be used to distinguish sputum from saliva and describe sputum characteristics? Researchers will compare a jet nebuliser with an E-flow Rapid nebuliser. Each participant will undergo sputum induction using both devices, with the order in which the devices are used determined at random. Participants will: * Attend two study visits, separated by at least 2 weeks * Receive a bronchodilator before sputum induction * Inhale hypertonic saline using either the jet nebuliser or E-flow Rapid nebuliser * Perform their usual airway clearance technique with supervision from a physiotherapist * Have their lung function, oxygen levels, heart rate, and chest sounds monitored * Provide sputum produced during the procedure for assessment and routine microbiological testing * Complete a brief questionnaire about their experience and the acceptability of each nebuliser device

Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis

The goal of this clinical trial is to support the development of personalized therapy tailored to each patient's individual characteristics. A better understanding of the pharmacokinetic profiles of elexacaftor, tezacaftor, and ivacaftor is essential to support Therapeutic Drug Monitoring (TDM) and to guide dose adjustments when clinically indicated, without compromising therapeutic efficacy. The study will include male and female patients aged ≥6 years with Cystic Fibrosis (CF) carrying at least one F508del mutation and receiving treatment with the elexacaftor/tezacaftor/ivacaftor combination for a sufficient period to achieve steady state. The main objective of the study is to characterize the steady-state plasma concentration profiles of elexacaftor, tezacaftor, and ivacaftor in patients with Cystic Fibrosis treated with the elexacaftor/tezacaftor/ivacaftor combination. Participants will continue their usual treatment with elexacaftor/tezacaftor/ivacaftor and ivacaftor according to the prescribed dosing schedule. During the study, they will attend regular clinical visits every 3 months for up to 12 months. At these visits, blood samples will be collected as part of routine clinical care and used to measure the plasma concentrations of the study drugs. Additional blood samples may be collected after the morning dose to better characterize drug levels over time. In a subset of participants, additional blood samples may be collected at several time points during the day to further assess the pharmacokinetic profile of the drugs. A single additional blood sample may be collected for pharmacogenetic analyses. Participants may also undergo a nasal brushing, as part of routine procedures, to obtain nasal epithelial cells for further analyses. Clinical information, including routine laboratory tests, vital signs, treatment information and any adverse events, will be collected throughout the study. The results of the pharmacokinetic and other laboratory analyses will not be used to modify the participant's treatment, which will remain under the responsibility of the treating physician.

Bacteriophages for Adults With Cystic Fibrosis and Chronic Achromobacter Lung Infection

The goal of this clinical trial is to learn if a new treatment called AchromoPhage is safe and well tolerated in adults with cystic fibrosis (CF) who have long-term lung infections caused by Achromobacter bacteria. AchromoPhage is a mixture of four naturally occurring viruses, called phages, that are designed to target and kill Achromobacter. This study will include 12 participants. People will be randomly assigned to one of three groups to receive AchromoPhage in different ways: by inhalation only, by intravenous (IV) infusion only, or by inhalation followed by IV infusion. Participants will: * Receive the study drug during clinic visits over a period of three weeks. * Provide blood, sputum, nasal, and oral samples so researchers can measure how the phages move through the body, how long they stay, and whether the body develops a response against them. * Complete breathing tests and quality-of-life questionnaires. The main question this study will answer is whether AchromoPhage causes any serious or treatment-limiting side effects in the first 42 days after dosing. Researchers will also look at changes in lung function, quality of life, phage levels in the body, and how the treatment affects Achromobacter and other bacteria in the lungs. The study is being run at the University of Pittsburgh (Pittsburgh, PA).

Impact of Trikafta on P2X7R and Clinical Outcomes in Cystic Fibrosis

The aim of this study is to assess the response of the ETI on P2X7R level as inflammatory marker and clinical outcomes in patients with cystic fibrosis.

A Prospective, Single-center, Open-label Study of Inhaled BMD003 (CFTR mRNA) in Chinese Adults With Cystic Fibrosis

The study uses a prospective, single-center, open-label clinical trial design to evaluate the safety and efficacy of inhaled BMD003 (CFTR mRNA) in adult Chinese patients with cystic fibrosis. This is a single-dose escalation study of nebulized inhaled BMD003 in patients with cystic fibrosis. The trial adopts sequential dose-escalation cohorts with flexible subject enrollment. Continuous safety monitoring will be performed throughout the study. If treatment-related adverse events meeting specified grade criteria occur during the trial, additional subjects will be enrolled at the current dose level for further safety observation. Subsequent dose escalation will proceed following a comprehensive safety evaluation of the prior cohort. The trial consists of three phases: a 2-week screening period, a 1-day drug administration period, and a long-term follow-up period of approximately 13 months. After successful screening and meeting eligibility criteria, subjects will be admitted on Day 1 to receive nebulized inhalation of the investigational product. Comprehensive safety observations will be completed on Day 2 prior to hospital discharge. Pharmacokinetic sampling and systematic safety assessments will be conducted at predefined study visits. All subjects will complete protocol-specified follow-up procedures after single-dose administration. Upon completion of this single-dose escalation phase, a multiple-dose study of BMD003 will be initiated. The detailed multiple-dose regimen will be defined based on preclinical findings and clinical data from this single-dose study, and implemented after ethical review and approval.

A Study to Evaluate Safety and Explore Efficacy of New Lipase NHS7108 in Adult Participants With Exocrine Pancreatic Insufficiency.

The purpose of this study is to measure the safety and explore the efficacy of 4 different doses of the new lipase NHS7108 in participants with EPI. In this study, all participants will take NHS7108 daily for 14 days and a matching dose of standard-of-care, pancrelipase (Zenpep®) for 14 days according to Treatment Sequence assignment. Both NHS7108 and Zenpep® are oral capsules that will be taken with each of the daily 3 meals and 2 snacks. Participants will interrupt all of their usual pancrelipase/pancreatin treatment for up to 8 days during screening and for the entire 2 treatment periods, where participants will take either the new lipase NHS7108 or a matching dose of the standard-of-care pancrelipase (Zenpep®). Participants will be asked to stay in a setting that allows controlled diet and 72-hour stool collection for approximately 7 days during the screening period and again for approximately 7 days at the end of each treatment period. During these 3 supervised periods, participants will receive a standardized diet with a predefined amount of fat and protein, stools will be collected in special containers and during the last day of the treatment period, blood samples will be obtained to measure fat absorption. These are essential to ensure valid assessment of participants' fat and protein absorption. Outside the 3 supervised periods, participants will be provided with guidelines and recommendations to create their own home-controlled meals and snacks according to their preferences for the remainder of the study duration. Number of Participants: The aim is to have 56 participants completing the study. Assuming approximately 14% drop-out rate, approximately 66 participants will be randomized to study intervention. Study Arms and Duration: The total study duration for each participant will be about 100 days (approximately 14 weeks), including: * A screening period of up to approximately 28 days (might be extended up to a total of 56 days) prior to the first dose administration. * A crossover treatment period (2 treatment periods: approximately 14 days each, with no washout in between). For each treatment period, study intervention will be administered 5 times a day (with 3 main meals and 2 snacks). After completion of Treatment Period 1, the participant will receive and start the new treatment for Treatment Period 2. * An end of treatment/early discontinuation visit within approximately 7 days of the last study intervention dose. * An end-of-study safety follow-up visit at 14 (±2) days after the last dose administration. Very low dose group: 10 mg NHS7108 (approximately 25,000 LU)/main meal and snack; 25,000 LU Zenpep/main meal and snack (50 mg NHS7108 \[approximately 125,000 LU\] per day; 125,000 LU Zenpep per day) Low dose group: 20 mg NHS7108 (approximately 50,000 LU)/main meal and 10 mg NHS7108 (approximately 25,000 LU)/snack; 50,000 LU Zenpep/main meal and 25,000 LU Zenpep/snack (80 mg NHS7108 \[approximately 200,000 LU\] per day; 200,000 LU Zenpep per day) Medium dose group: 40 mg NHS7108 (approximately 100,000 LU)/main meal and 20 mg (approximately 50,000 LU) NHS7108/snack; 100,000 LU Zenpep/main meal and 50,000 LU Zenpep/snack (160 mg \[approximately 400,000 LU\] NHS7108 per day; 400,000 LU Zenpep per day) High dose group: 60 mg NHS7108 (approximately 150,000 LU)/main meal and 30 mg NHS7108 (approximately 75,000 LU)/snack; 150,000 LU Zenpep/main meal and 75,000 LU Zenpep/snack (240 mg NHS7108 \[approximately 600,000 LU\] per day; 600,000 LU Zenpep per day). The dose for participants \< 60 kg who are assigned to the high dose group will need to be weight-adjusted to ensure that they receive no more than 10,000 LU/kg/day.

Nutrition Supplement for Cystic Fibrosis

The goal of this study is to learn if one nutrition supplement formula works better than a different formula in adults with cystic fibrosis. The main question being addressed is: Will certain atypical versions of certain nutrients outperform typical versions of these nutrients? This will be determined by examining blood measures of nutrient levels and/or indications of nutrient function indicators pre- and post-intervention. Participants will take the supplements for 6 weeks with a blood draw before and after that time.

CGM Dynamic Index for Predicting Prediabetes in Cystic Fibrosis

The primary objective of this pilot study is to develop a CGM-based model to predict the progression from prediabetes to diabetes in individuals with cystic fibrosis.

Proof-of-concept Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of SION-719 When Added to Trikafta

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SION-719 when given to people with CF who are already taking Trikafta.

Safety, Tolerability, and Pharmacokinetics of Multiple Dose Combinations of SION-451 and Complementary Modulators SION-2222 and SION-109 in Healthy Participants.

The purpose of Parts D and E of this Phase 1 study are to evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants.

MRI Parameters as Biomarkers in Cystic Fibrosis (FEMPTO)

Cystic fibrosis (CF) is an inherited condition that affects several organs, including the gut. People with CF often experience uncomfortable digestive symptoms such as bloating, gas, abdominal pain, and constipation. The root cause is that the gut produces thicker-than-normal mucus, which slows things down and makes it harder for the bowel to work properly. Current treatments such as laxatives, enemas, or surgery can be inconvenient and don't always work well. There is a real need for better options, and for a clearer understanding of how the CF gut behaves and responds to treatment. This study will use MRI, a non-invasive imaging technique, to look at how fluid moves through the gut in adults with CF and the impact of linaclotide. Linaclotide is a licensed medication used to treat chronic constipation and irritable bowel syndrome. It works by encouraging the gut to release more fluid, helping things move more easily. It acts locally in the gut and is not absorbed into the bloodstream. Early research suggests it may help in CF in a way that does not rely on correcting the underlying genetic fault, making it a promising avenue to explore. Participants will include people with different bowel habits, including those who tend towards constipation and those who tend towards diarrhoea. The scans will help researchers check whether certain MRI measurements can reliably detect changes in gut fluid and movement. This is a feasibility study; its main objective is to test whether these MRI measurements are useful and practical, and support a sample size calculation, in future CF studies investigating linaclotide effects.

Environmental Reservoirs of Non-tuberculous Mycobacteria in Cystic Fibrosis Households

This multicenter, non-interventional case-control study investigates whether household environmental reservoirs, particularly water systems, are associated with non-tuberculous mycobacterial (NTM) infections in people with cystic fibrosis (CF). Environmental samples from the homes of CF patients with and without NTM infection will be analyzed and genetically compared with available clinical isolates, alongside assessment of environmental risk factors, to improve understanding of exposure pathways and inform future prevention strategies.

Machine Learning Prediction of Pulmonary Function in Children With Cystic Fibrosis

Cystic fibrosis is a multisystem genetic disorder characterized by progressive pulmonary impairment and extrapulmonary limitations. This retrospective observational study will perform a secondary analysis of previously collected data from children with cystic fibrosis. The primary objective is to determine the relative contribution of peripheral muscle oxygenation and postural balance parameters to the prediction of pulmonary function, including forced expiratory volume in 1 second, forced vital capacity, and peak expiratory flow, using machine-learning regression methods. The additional contribution of exercise-related oxygen saturation responses, symptoms, nutritional and anthropometric characteristics, physical activity, respiratory muscle function, quality of life, treatment burden, and disease-related clinical variables will also be examined. No new assessment, intervention, or participant contact will occur.

Heart and Blood Vessels Health in People With Cystic Fibrosis

Cystic fibrosis (CF) is a disease that affects over 11,000 people in the UK. It is a genetic condition that affects many organs including the lungs, pancreas, kidneys and liver. New drugs called "modulators" have meant people with CF are now living much longer. Until recently, heart disease was rare in CF, but with the new modulators there are increasing concerns that heart disease may become a big problem in the future. This is partly to do with the drugs causing weight gain and higher blood pressure, which are risk factors for heart disease. My PhD project aims to find out whether the blood vessels and hearts of people with CF are healthy or diseased. I will then find out how the blood vessels are changing over time and work out what things are driving those changes. I will measure the health of the blood vessels and heart using an ultrasound machine to understand what the pattern of disease is like and who might be at the highest risk for heart disease in the future. I will then repeat these measurements a year later. I will compare people of different ages and with different types of disease to understand what things may help us identify heart disease as soon as possible. In the general population, doctors often use medical prediction tools to find out who is at the highest risk for heart disease. We do not know if these work for people with CF, so I will also find out whether those prediction tools are useful in CF. It is vital to understand who may be at risk for heart disease, as one of the most effective ways of treating heart disease is to prevent it from happening. This work may pave the way for future studies to test early treatment for heart disease in those people we identify might be at high risk. Early prevention treatment could reduce the risk of heart disease and ultimately improve the length and quality of life of people living with CF. This is particularly important given people with CF already have a much shorter life expectancy than the general population. In summary, this PhD project will help improve our understanding of heart disease in CF and help identify the best way forward to prevent heart disease causing health problems related to heart disease for these individuals in the future.

Autogenic Drainage Versus Mechanical Percussion in Children With Cystic Fibrosis

The goal of this clinical trial is to compare the effects of autogenic drainage and mechanical percussion on lung function, dyspnea, and quality of life in children with cystic fibrosis. The main questions it aims to answer are: * Does autogenic drainage improve lung function more effectively than mechanical percussion in children with cystic fibrosis? * Does autogenic drainage reduce dyspnea (breathlessness) more effectively than mechanical percussion? * Does autogenic drainage improve health-related quality of life more effectively than mechanical percussion? Researchers will compare autogenic drainage with mechanical percussion to determine which airway clearance technique provides greater benefits for children with cystic fibrosis. Participants will: * Be randomly assigned to receive either autogenic drainage or mechanical percussion therapy. * Participate in supervised treatment sessions five times per week for six weeks. * Undergo assessments of lung function using spirometry (FEV₁ and FVC), dyspnea using the Modified Borg Dyspnea Scale, and quality of life using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) before and after the intervention period. The findings of this study may help identify the most effective airway clearance technique for improving respiratory health and quality of life in children with cystic fibrosis.