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).

Verapamil Effect in Cystic Fibrosis-related Dysglycemia

The investigators are conducting a pilot open-label pre/post interventional trial in adolescents and adults with cystic fibrosis (CF) and abnormal glucose tolerance or early CF-related diabetes mellitus (CFRD) to assess the safety and efficacy of verapamil on beta cell function and dysglycemia.

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.

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.

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).

Gastrointestinal Response of Pediatric Cystic Fibrosis Patients on Mediterranean Diet

There is no study to date that has evaluated the impact or effect of a Mediterranean diet in children with CF. The goal of this study would be to help provide better guidance around questions the investigators, as CF care providers continue to receive from patients and families about how to best promote overall health in pediatric cystic fibrosis from a dietary perspective. Currently, the updated nutritional recommendations are variable and broad. Parents continue to search for more concrete guidance about how best to promote long-term health given the ever-increasing life expectancy of cystic fibrosis patients in this new area of advanced therapeutics. Given the changing landscape of the CF care in general, children are less likely to struggle with early life malnutrition, and it is becoming increasingly clear that high fat, high calorie diets are not beneficial nor are necessary for all children with CF.

Safety of Stopping Pancreatic Enzyme Replacement Therapy in Children With Improved Pancreatic Function After Highly Effective Modulator Therapy

The goal of this clinical trial is to evaluate the safety of stopping pancreatic enzyme replacement therapy (PERT) in children with cystic fibrosis (CF) receiving CFTR modulator therapy (CFTRm) who have regained pancreatic sufficiency. The main questions it aims to answer are: 1. Does discontinuation of PERT affect gastrointestinal symptoms, nutritional status, pancreatic function, or body composition over 6 months? 2. Does stopping PERT increase gastrointestinal symptoms or affect nutritional status, pancreatic function, or body composition compared with continuing PERT? Researchers will evaluate changes in growth, gastrointestinal symptoms, vitamin levels, pancreatic function, and body composition following PERT discontinuation. Participants will: * Complete study visits and assessments over 6 months * Continue or discontinue PERT based on study assignment * Undergo anthropometric measurements * Complete questionnaires about gastrointestinal symptoms * Provide blood samples to assess vitamin levels and coagulation markers * Provide stool samples to measure fecal elastase-1 (FE-1) and evaluate pancreatic function

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.

Evaluation of Ventilation Defects Downstream of Mucus Plugs in Patients With Muco-Obstructive Lung Disease

In this study, xenon MRI will be used to evaluate regional functional consequences of mucus plugs in the lungs of patients with muco-obstructive pulmonary disease. Mucus plugs will be identified using CT imaging, and xenon MRI will be used to evaluate ventilation and gas exchange impairments in regions of the lungs corresponding to the airways downstream of mucus plugs.

Home Air Pollution in Children With Cystic Fibrosis Study

Cystic Fibrosis (CF) is a devastating chronic pulmonary disease that continues to cause significant morbidity and mortality despite great advances in therapies. Hispanic children with CF have worse outcomes, including higher mortality and more severe pulmonary disease, than non-Hispanic white children with CF. It is not known why Hispanic children with CF have more severe disease as it is not explained by CFTR genetic severity, diagnosis age, or socioeconomic status. The health disparities have worsened, not improved, for Hispanic children with CF since the development of new disease-altering therapeutics, CFTR modulators. It is critical to determine what is contributing to lung disease severity in Hispanic children with CF. Non-genetic factors, including environmental exposures, are estimated to account for 50% of lung disease severity variability in CF. Air pollution exposure during early childhood is associated with lower pulmonary function in healthy children and severe lung disease in children with asthma. However, air pollution exposure is vastly understudied in other chronic pulmonary diseases of childhood, such as CF. Investigating air pollution exposure in CF may provide vital information about the drivers of health disparities in Hispanic children with CF and about the environmental exposures influencing lung disease severity across all children with CF. To investigate air pollution exposure in children with CF, the investigators have assembled a multidisciplinary team of international experts in air pollution exposure, CF lung disease, health disparities, and pulmonary microbiome. The investigators will use two phenomenally rich databases, the CF Foundation Patient Registry and the University of Washington Spatiotemporal Air Pollution Exposure Model, to investigate the first aim: 1A) To determine whether neighborhood-level ambient air pollution exposure during childhood differs between 1500 Hispanic and 8500 non-Hispanic white cwCF in the CF Foundation Patient Registry, and 1B) To determine if neighborhood-level ambient air pollution exposure is associated with lung disease severity in Hispanic and non-Hispanic white cwCF. Across six geographically diverse clinical research CF centers, the investigators will enroll 100 Hispanic and 100 non-Hispanic children with CF to investigate the following aims: 2) To assess differences in residential indoor and ambient air pollution exposures by ethnicity in 200 cwCF, as well as the association between such exposure and pulmonary function by ethnicity, 3) To investigate the association of indoor and ambient air pollution exposure on airway inflammation and microbiome diversity and composition in Hispanic and non-Hispanic white cwCF using metatranscriptomic RNA sequencing. The HEROIC-CF Study is poised to advance the knowledge of the effect of air pollution exposure on not only CF lung disease severity, but may be a model to understand environmental exposures on disease severity in other chronic pulmonary diseases of childhood.

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

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.

Ensuring Access to Optimal Therapy in CF: The ENACT Study

This clinical trial is examining the action and effects of several new drugs in the treatment of cystic fibrosis in children. In addition, several genetic factors are examined. The hope is that the ability to determine prior to treatment those individuals who will or will not respond to existing therapies will avoid needless risk of side effects and the high cost of a potentially ineffective treatment regimen. Understanding the way these drugs work in the body and the best way to study them is critical to expanding the use of these drugs to all patients with cystic fibrosis (CF).

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.

Muscle Fatigue in People With Cystic Fibrosis: Insight From a Mobile App

Muscle fitness is an important component of health. For instance, the ability to resist to muscle fatigue development is important for daily functioning. Previous studies have suggested altered muscle function in people with cystic fibrosis. However, it is unclear whether such findings still apply in the modern era of CF. Several studies suggested that recent improvements in therapeutics, including CFTR modulators, may have positive effects on the skeletal muscles, potentially normalizing the ability to resist to muscle fatigue. However, no studies to date compared muscle fatigue between people with cystic fibrosis and healthy controls in a large sample of patients. One difficulty is that muscle fatigue assessment requires high-cost dynamometric instruments, which also leads to a gap between research and clinical practice. Our research group has created a mobile application based on video analysis of the chair rising test that reports values of time, velocity and power as reliable as devices found in a laboratory environment. The application has been shown to be valid and reproducible for measuring muscle fatigue in healthy people. However, a validation is necessary before recommending its use in people with cystic fibrosis.

Routine Validation and Reproducibility Testing of Laboratory Assays and Research Techniques Used for Endocrine, Cardiometabolic, and Musculoskeletal Disorder Research (VALD)

The purpose of this research study is to validate (check the accuracy of) laboratory assays, intravenous catheter insertion, and equipment or devices and their reproducibility, which is necessary to perform high quality research on chronic diseases, nutrition, and metabolism (the process by which a substance is handled in the body) at the University of Missouri. As technology changes and uses new testing methods, it is necessary to compare results from old tests, equipment and devices and new tests, equipment, or devices and the reproducibility of these measurements to make sure the results are accurate. Reproducibility means performing the same test more than once to see if the same results can be achieved each time. This study will look at the validation and reproducibility of tests and laboratory assays in participants who are healthy or affected by relevant endocrine, cardiometabolic, and musculoskeletal disorders.

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.

Proof of Principle Study for an Efficacy Trial of Linaclotide for Cystic Fibrosis

Linaclotide is a medicine used to treat constipation and irritable bowel syndrome with constipation (IBS-C). It works by acting on the surface of the gut lining, where it increases the movement of salt and water into the bowel. This softens stools, makes them easier to pass, and can also reduce gut pain One advantage of linaclotide is that, unlike some natural substances in the gut, it is stable and can act throughout the intestine. Studies in animals show that it has the strongest effect in the upper small intestine, but it may act in other parts of the bowel as well. In people, however, it is not yet clear whether linaclotide mainly works in the small intestine or in the large intestine (colon). Knowing this is important, because it could help the investigators understand whether linaclotide might also be useful in other conditions, such as cystic fibrosis, where the gut does not handle fluid properly. Linaclotide is taken as a capsule, but less than 1% is absorbed into the bloodstream. Instead, it stays in the gut, where it is broken down into smaller active parts. This means both the small intestine and colon may be exposed to its effects. Until now, it has been hard to study this because traditional methods only measure one part of the gut at a time. A team at the University of Nottingham has developed MRI scanning methods that can safely and non-invasively measure water content in the small intestine and colon. The aim of this pilot study is to use MRI in healthy volunteers to see exactly where linaclotide acts. This knowledge will help optimise future studies in conditions such as 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).

Kidney Function in People With Cystic Fibrosis in the Era of HEMT

The purpose of this study is to find out what causes kidney disease in people with CF. The investigators will study biomarkers in the blood and urine that can either predict who is at risk or detect kidney damage early before it becomes permanent. The study will compare these markers in people with CF over time and during the treatment of lung flare-ups. It will also compare the blood and urine samples obtained from people without CF. The comparison aims to better understand the impact of cystic fibrosis and its treatment on the kidneys, as well as to develop improved methods for preventing, diagnosing, and treating kidney issues associated with CF.

Group Cognitive Behavioural Therapy for Adults With Cystic Fibrosis

The overall goal of this clinical trial is to: a) explore the feasibility, acceptability, and participant experiences with the group version of CF-CBT; b) examine the effectiveness of the virtual delivery of a group version of CF-CBT in reducing depression and anxiety symptoms, perceived stress, coping skills, and health related quality of life among adults with CF. The primary research questions is: • How feasible and acceptable (i.e., drop out, adherence, and satisfaction) is virtual, group CF-CBT? The secondary research questions is: • How will virtual, group CF-CBT affect depression and anxiety? The tertiary/other research questions are: * How will virtual, group CF-CBT affect perceived stress, coping skills, and health related quality of life? * What is the association between group cohesion and depression, anxiety, perceived stress, coping skills, and health related quality of life? Participants will: * Complete short demographic questionnaire regarding their personal and health information. * Complete questionnaires about symptoms of depression, anxiety, perceived stress, coping skills, and health related quality of life at pre- and post-program. An additional measure of treatment expectancy will be completed at pre-program only. At post-program only, measures of group cohesion and treatment satisfaction will be completed. * Complete the CF-CBT online mental health program over eight weeks. * Be invited to complete an interview about their experiences with the program. Primary outcomes will be compared to benchmark study of individual CF-CBT. Secondary outcomes (i.e., depression, anxiety) will be compared against themselves (i.e., pre- and post-group). Tertiary/other outcomes (i.e., perceived stress, coping skills, health related quality of life) will be compared against themselves (i.e., pre- and post-group). The associations between self-reported outcome measures and group cohesion will be analyzed by computing Pearson correlation coefficients.

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.

MAGNIFY - Pulmonary Magnetic Resonance Imaging for Cystic Fibrosis

This research study is looking at new ways of measuring the function of the lungs in patients with cystic fibrosis. This study is using the most advanced methods for measuring lung function including 2 tests called hyperpolarised gas magnetic resonance imaging (HP MRI) and multiple breath washout (MBW), to better understand changes in the lungs over time. HP MRI involves taking pictures of the air in your lungs after breathing in a harmless gas (xenon). MBW is a breathing test used to calculate something called the lung clearance index (LCI). By measuring these tests on the same day, alongside standard lung function tests, we aim to understand lung function in greater detail than ever before.

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.