Clinical Research Directory

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) and the University of California San Diego (San Diego, CA).

Exercises' Effect on Muscle Strength, Aerobic Capacity and Respiratory Functions in Cystic Fibrosis

This research aims to evaluate the effects of upper and lower limb exercises on muscle strength and pulmonary function in children diagnosed with CF. While aerobic training is a known component of CF management, resistance training focused on specific limb groups has gained attention for its additional benefits. Upper limb exercises may aid respiratory muscle endurance and thoracic mobility, enhancing pulmonary mechanics. In contrast, lower limb exercises (such as cycling or squats) are associated with improved oxygen consumption (VO₂ peak), enhanced mobility, and greater lower body strength. This randomized clinical trial will be conducted using a non-probability convenience sampling technique. The study will take place at the pediatric cystic fibrosis centers of Gulab Devi Chest Hospital and The Children's Hospital, Lahore. The targeted population includes children aged 6 to 18 years who have been diagnosed with cystic fibrosis and referred to the physiotherapy department. The study duration will be ten months following the approval of the synopsis. Eligible participants will be children aged between 6 and 18 years, clinically diagnosed with cystic fibrosis, currently stable with no history of hospitalization or significant lung infection in the past month. They should be physically able to participate in exercise and capable of following instructions, with informed consent obtained from their parents or guardians. Children will be excluded if they suffer from other severe lung diseases, cardiovascular or orthopedic conditions that restrict exercise, recent surgery or hospitalization within the last month, or if they are unable to understand instructions. Those dependent on oxygen therapy or ventilator support at all times will also be excluded. The primary outcome measures will include lung function assessed by spirometry (FVC, FEV1), sputum production recorded through a sputum diary, and aerobic capacity measured by the Incremental Shuttle Walk Test (ISWT). Muscle strength will be evaluated for both upper and lower limbs, using a handheld dynamometer for the upper limbs and the Sit-to-Stand Test for the lower limb

Physical Impairments in Children With Cystic Fibrosis

It is aimed to reveal impairments regarding urinary incontinence, dyspnea, muscle strength, functional capacity or quality of life in children and adolescents with cystic fibrosis compared to healthy children and adolescents.

Understanding Inflammation, InFection and Interventions in Severe Exacerbations of Cystic Fibrosis

The UNIFIED-CF study is an observational study designed to investigate the impacts of treatment given for severe pulmonary exacerbations in people living with cystic fibrosis (pwCF). Exacerbations are episodes when pwCF become more unwell, typically characterised by increased cough, sputum, and breathlessness and treated with a combination of oral and/or intravenous antibiotics. Severe exacerbations require treatment with intravenous antibiotics and impart considerable morbidity on pwCF. In this study, the investigators will recruit people at risk of severe CF exacerbations when they are well and if/when they are subsequently admitted for treatment of an exacerbation, the investigators will track symptoms and lung function during recovery, and collect blood, sputum and stool samples to allow us to explore the biological mechanisms of exacerbations and how they relate to different treatment responses. The study is event driven and will complete recruitment once 125 participants have completed treatment and follow-up for a severe exacerbation event. This study is funded by the Cystic Fibrosis Trust. This study is part of a wider programme of research, led by the PULSE-CF Innovation Hub (and hosted by the University of Manchester). The aim of the Hub is that the data from the UNIFIED-CF study will ultimately support the design of a platform clinical trial to test exacerbation-prevention interventions in CF.

Identifying the Causes and Risk Factors of Pulmonary Exacerbations in Cystic Fibrosis

The CF-Tracker study is a community surveillance study, designed to understand the causes of exacerbations in people with cystic fibrosis (CF) (pwCF). These are episodes when pwCF become more unwell, typically characterised by increased cough, sputum, and breathlessness, and requiring prolonged courses of oral or intravenous antibiotics. This observational study applies a two-tiered approach over 12 months. It will recruit 200 pwCF to Group A, and an additional 100 pwCF to Group B, which follows the same format but includes additional in-clinic sampling. Participants will provide longitudinal clinical data and biological samples. Group B will be offered at 5 specialist CF centres (Manchester, Cardiff, Newcastle, Leeds, Liverpool), will include additional sampling methods at clinic visits, and additional scheduled clinic visits at 1 month and 6 months. Group B participants will be offered an in-person visit if they become unwell, so that samples can be collected before they start antibiotics. In Group B, those attending the Manchester clinic will have the option of taking part in a 12 month home environmental and pollution monitoring, and sleep monitoring (both optional arms). A pilot study will test the practicalities of running the same protocol in a paediatric population. This will consist of up to 25 children with CF (5-15 years) attending a paediatric clinic in one of the four core centres. Up to 40 healthy volunteers will be recruited to provide samples on a single occasion as controls. This study is funded by the Cystic Fibrosis Trust. This study is part of a wider programme of research, led by the PULSE-CF Innovation Hub (and hosted by the University of Manchester, www.pulse-cf.com). The aim of the Hub is that the data from CF-Tracker will support the delivery of a platform clinical trial to test exacerbation-prevention interventions in CF.

Personalized Mobile Health Platform to Promote Physical Activity in Adolescents and Young Adults With Cystic Fibrosis

The goal of this clinical trial is to help adolescents and young adults between the ages of 13-25 with Cystic Fibrosis (CF), medically stable, able to speak and read English, and are not experiencing a CF - related exacerbation, who are already active to remain, or gradually encourage them to increase their levels of physical activity Participants will be asked to utilize a smartphone program, called NUDGE that we have developed. NUDGE is a chatbot with evidence-based features known to help teens make progress toward health goal: * Set and review goals * Self-monitor progress * Provide feedback on goal attainment * Revise future goals

MRI Assessment of Lung Airways in Cystic Fibrosis: Evaluate MRI's Ability to Detect Changes in Airway Structure .

This study is being done to determine whether MRI can produce high quality lung and airway images in healthy and CF patients and if MRI can be used to evaluate size and shape of the airways with computer assistance. This study will also repeat MRI experiments two years after the initial MRI scan to see if changes to airway size and shape are seen over time. In a subset of participants, we will investigate whether MRI results are repeatable and reproducible in the short-term one week after the initial MRI visit. This study will help understand if MRI based measurements of airway size and shape can be used as a monitoring tool that does not use x-ray radiation in patients with 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.

ACT With CF Self-Help Toolkit

Acceptance and Commitment Therapy (ACT) tailored to meet the needs of adults living with cystic fibrosis (ACT with CF) is a newer form of talk therapy that has been shown to reduce anxiety \& depression and improve psychological flexibility, and value-based living. The investigators are now trying to find out whether a self-help version of this treatment (ACT with CF - Self Help Toolkit) is also effective in reducing anxiety and depression and improving psychological flexibility and value-based living in adults with CF. Adults with cystic fibrosis are at increased risk for anxiety and depression. This study examines whether a patient-facing therapy, ACT with CF - Self Help Toolkit can help to reduce anxiety and depression among adults with CF. This treatment can be accessed on the participant's smartphone.

Characterisation of a Population of Adults Suffering From Cystic Fibrosis in a Belgian Reference Center

This research project aims to better understand the consequences of diabetes on the quality of life, respiratory function, and nutritional status of patients with cystic fibrosis followed at a Belgian reference center and to compare the quality of life of patients with cystic fibrosis depending on whether or not they have diabetes.

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.

Population Pharmacokinetics of Elexacaftor-tezacaftor-ivacaftor in a Paediatric Population

Cystic fibrosis is a rare, progressive genetic disease caused by a mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Respiratory and nutritional effects are crucial to patients' prognosis. Since the early years of 2010, etiological treatment has been based on the use of CFTRm (CFTR modulator), which aim to restore the function of the mutated protein. Initially used as monotherapy and targeting a limited number of patients, CFTRm has gradually been extended to a larger number of patients, to the point where it now concerns 9 out of 10 patients, through the use of triple therapy with Elexacaftor-Tezacaftor-Ivacaftro (ETI) or Kaftrio(R). The efficacy of triple therapy is spectacular, revolutionizing the prognosis of the disease. However, the potential for neuropsychological side-effects (20-50% depending on age, but more frequent in young children under 5) and hepatic side-effects (hepatic cytolysis) must be taken into account. A better understanding of pharmacokinetic variability in children, as well as the relationship between exposure to therapeutic effects and adverse reactions, is therefore particularly important. The aim of this study is to measure the association between the pharmacokinetic parameters of Elexacaftor, Tezacaftor and Ivacaftor (plasma clearance and volume of distribution) and therapeutic or adverse effects in pediatric patients with cystic fibrosis treated with the combination.

Clean Air for Rare MUcociliary Clearance dIsorders

The goal of this clinical trial is to learn whether using a high efficiency particulate air (HEPA) air purifier can improve respiratory health in children and adults with Cystic Fibrosis (CF) or Primary Ciliary Dyskinesia (PCD). The main questions it aims to answer are: Can using a HEPA air purifier at home reduce respiratory symptoms in people with CF or PCD? Can it improve lung function and overall health? Researchers will compare participants' health outcomes before and after the use of the HEPA air purifier to see if cleaner indoor air makes a measurable difference. Participants will: Visit the clinic for baseline health assessments (such as lung function and symptom questionnaires). Have two HEPA air purifiers installed in their home. One device will be placed in the main living area and one in the bedroom. Undergo exposure assessments during home visits to measure indoor air quality.

A Prospective Study of Advanced Diagnostics in People With an Unclear Diagnosis of Cystic Fibrosis

Sometimes it is very difficult to tell if someone has cystic fibrosis (CF), especially when they have rare CF genes. Without this certainty, they are unlikely to get the correct treatment so their health may be affected. More accurate ways to test for CF are therefore needed in this situation. The aim of this study is to develop a more accurate test using what are called "organoids" or "mini organs." Organoids are grown in the laboratory from a small piece of gut tissue. As they have the person's exact genes, they can show if the CF gene ("CFTR") is working correctly or not and thus if the person has CF. The investigators will compare the organoid response with the current more established tests, such as the sweat test and CF genetics, and other recognised specialist tests called nasal potential difference (NPD) and intestinal current measurement (ICM). The gut tissue is usually taken by a quick, relatively painless, outpatient procedure (rectal biopsy). The additional benefit of organoids is that they can also help us to work out the best treatment for that individual by testing how well the gut tissue responds to different drugs in the laboratory. The investigators wish to carry out this research to prove that gut organoids are a better way to test for CF in this situation. The goal will be to diagnose people faster and for them to get better treatment quicker, both key for leading a longer and healthier life.

CF Wellness Program

This study is a pilot randomized control trial (RCT; N=80) comparing the Cystic Fibrosis Wellness Program (CFWP) to usual care (UC) to evaluate (1) Intervention Adherence (completion of the CFWP Coaching Sessions) (2) Study Retention (completion of the Week 15 assessment) and (3) Data Quality (valid daytime and nighttime fitness tracker data). A secondary aim is to gather preliminary data to determine if the CFWP has a clinically significant signal over usual care to improve fatigue, sleep, and physical activity (PA) and reduce sedentary behavior.

Studying the Presence of CFRD Complications With Thoughtful Recruitment (SPeCTRuM)

This multicenter cross-sectional study will include a diverse population of adolescents and adults with CF. The overall Aim is to describe prevalence of diabetes microvascular complications and macrovascular surrogates in people with established CFRD.

Environmental Reservoirs of Non-tuberculous Mycobacteria in Cystic Fibrosis Households: A Case-control Study of Exposure Risk at Home

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. 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.

Impact of Elexacaftor-Tezacaftor-Ivacaftor Treatment on Metabolic, Epigenetic and Fecal Microbiota Profiles in People With Cystic Fibrosis.

Cystic Fibrosis (CF) is a genetic disease that affects multiple organs and systems. In recent years, the marketing of CFTR protein modulator drugs, such as the Elexacaftor-Tezacaftor-Ivacaftor (ETI) combination, has significantly improved patients' quality of life and prognosis. ETI, currently prescribed in Italy for CF patients over six years of age with at least one F508del mutation, has shown improvements in lung function, nutritional status, and a reduction in pulmonary exacerbations. In the coming months, ETI will be prescribable for patients aged $\\ge$ 2 years with at least one F508del mutation; furthermore, the EMA recently approved its use in all patients aged $\\ge$ 2 years, including those with mutations other than F508del (excluding patients with homozygous Class I mutations).Recent studies also highlight an impact on systemic metabolism, with an increase in blood cholesterol levels, blood pressure, and nutritional status, leading to a marked increase in patients with obesity. This could result in an increased long-term cardiovascular risk, especially in children with CF. Additionally, early data show that ETI also induces changes in the gut microbiota and epigenetic modifications by altering DNA methylation, particularly in genes crucial for the onset of CF-related complications, such as diabetes.The gut microbiota of CF patients differs from that of healthy controls, and ETI appears to improve microbial diversity while reducing intestinal inflammation and antibiotic resistance genes. Although ETI-related adverse events are mostly mild and similar to typical respiratory exacerbation symptoms (cough, headache, pharyngodynia, or transient bronchospasm), concerning side effects such as neuropsychiatric effects, intracranial hypertension, or liver failure have also been reported. Currently, it is not possible to predict which patients are at a higher risk of adverse events, but it is known that some of these are related to the blood levels of ETI's individual components. Therefore, monitoring these levels could be useful for dose optimization and reducing the risk of adverse events.Despite the publication of numerous real-world studies on the efficacy and safety of ETI and the sharing of recent standards of care for CF patients on modulator therapy, prospective studies are desirable, especially in the pediatric population. These are needed to monitor metabolic and epigenetic parameters, as well as changes in the fecal microbiota, correlating them with the blood levels of individual ETI components.

Prevalence of Exercise-induced Ventilatory Limitation and Associated Factors in Patients With Cystic Fibrosis Receiving Elexacaftor-Tezacaftor-Ivacaftor

Cystic fibrosis is a genetic disorder affecting the entire body and associated with respiratory exacerbations, impaired quality of life and reduced life expectancy. The therapeutic management of cystic fibrosis has been profoundly changed by the recent arrival of a combination of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Elexacaftor-Tezacaftor-Ivacaftor (ETI), which improve quality of life, respiratory function and reducing the number of exacerbations. The impact of these treatments on exercise adaptation has not been clearly identified. The main objective is to estimate the prevalence of ventilatory reserve amputation during submaximal exercise testing assessed by the 6-minute walk test (6MWT) in patients with cystic fibrosis treated with ETIs.

Study to Enable New Diagnostics for Pulmonary Microbes in People With CF

Sputum culture has been the best approach to detect harmful bacteria in the lungs of people with cystic fibrosis (CF). With the widespread use of new CF therapies (like Trikafta and Alyftrak), it is more difficult for people with CF to produce sputum even though they still have harmful bacteria in their lungs. The SEND-CF study is being done to see if there are other ways to detect harmful bacteria in the lungs.

The School-Age Children With Cystic Fibrosis and Their Parents on Health Literacy

This randomized controlled experimental study is planned to examine the effect of an online education program provided to school-age children aged 6-11 years diagnosed with cystic fibrosis and their parents on health literacy levels. The study population will consist of 123 school-age children with cystic fibrosis and their parents who are followed at the Cystic Fibrosis Outpatient Clinic of Marmara University Pendik Training and Research Hospital. The study sample will include 104 children and their parents, who will be randomly assigned to either the intervention group (n = 52) or the control group (n = 52). Data will be collected using the Introductory Information Form, the Health Literacy Scale for School-Age Children, and the Turkey Health Literacy Scale-32. Following the pre-test assessments, an online education program developed by the researcher will be delivered to the intervention group. The control group will not receive any additional intervention. Both groups will complete post-test assessments four weeks after the pre-test.

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.

Novel Sensors and Artificial Intelligence for Detection of Acute Pulmonary Exacerbations in Cystic Fibrosis and Bronchiectasis

The goal of this observational study is to learn about new sensors that measure changes in the body that happen during a chest infection, such as breathing rate and heart rate. This study will be with adults who have either cystic fibrosis or bronchiectasis who start treatment with intravenous antibiotics (usually for around 2 weeks). The main question it aims to answer is the change in sensor measure (such as heart rate) between the start and end of treatment for a chest infection. No follow up visits are required for this study.

Sinonasal Therapies and Histologic Correlations of Patients With Cystic Fibrosis in the Era of Highly Effective Modulator Therapy

The investigators are doing this study to discover if it is appropriate for people with Cystic Fibrosis (CF) on highly effective modulator therapy (HEMT) to stop using certain standard Sino nasal therapies such as high-volume nasal saline irrigations, topical nasal steroids, and topical nasal antibiotics. They are also going to study the fluid inside the nose to see if there are changes when stopping these therapies. Right now, they are not sure if it is suggested to stop these treatments when patients begin highly effective modulator therapy (HEMT)