Clinical Research Directory

Renal Denervation in Patients With Atrial Fibrillation and Hypertension

High blood pressure is a major risk factor for atrial fibrillation (AF), an irregular heart rhythm, and heart failure with preserved ejection fraction (HFpEF), a condition in which the heart becomes stiff and cannot relax properly. Both conditions can significantly affect quality of life and frequently occur together. In individuals with high blood pressure, increased activity of the nerves surrounding the kidneys can further elevate blood pressure and contribute to strain on the heart. Renal denervation (RDN) is a procedure designed to lower blood pressure by reducing the activity of these nerves using a thin catheter and controlled energy. RDN has been shown to lower blood pressure safely in many patients; however, the potential benefits in individuals with concurrent AF and HFpEF remain uncertain. This pilot study will be conducted in two phases. Phase 1 will assess the safety and feasibility of accessing the renal arteries and evaluating blood pressure responses to brief electrical stimulation of the renal nerves.

A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF)

A Safety, Tolerability, and Biomarker Trial of VS-041 in Participants with Heart Failure with Preserved Ejection Fraction (HFpEF)

Treating Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: Ablation or Medication

This study is testing two different ways of treating atrial fibrillation (AF) in people who also have heart failure with mildly reduced or preserved heart function. Patients will randomly be assigned to either rhythm control using catheter ablation or rate control using medicines. The pilot phase will determine if a larger study can be successfully carried out to see which approach better improves survival, reduces hospitalizations, and enhances quality of life.

Pharmacological Optimization in Prevention in Heart Failure: A Sex-gap?

The goal of this clinical trial is to learn whether a rapid and intensive optimization of heart failure medications in women can improve outcomes after hospitalization for heart failure. It will also investigate the safety and the tolerance of these treatments when given at full guideline-recommended doses. The main questions it aims to answer are: 1. Does intensive medication optimization reduce death or hospital readmissions for heart failure within one year? 2. Do women benefit as much as men from intensive and full-dose heart failure therapy? 3. Is this treatment protocol safe and feasible also in women? Researchers will compare two groups of women hospitalized for heart failure: * High-intensity care: starting and increasing all recommended heart-failure medications as quickly as possible and monitoring patients closely during the first weeks after discharge. * Usual care: medications are started and adjusted gradually, according to the judgment of the treating cardiologist and the patient's usual care team. The study will follow participants for 12 months to see whether the high-intensity strategy reduces death, hospital readmission for heart failure, or worsening symptoms. It will also evaluate side effects, medication tolerance, and quality of life. Participants will be randomly assigned to one of the two groups, attend regular follow-up visits for one year, complete a short quality-of-life questionnaire (EQ-5D). This study will include about 360 women from 13 hospitals in Italy. It is sponsored by IRCCS Policlinico San Donato and funded by the Italian Medicines Agency (AIFA).

Resmetirom in Patients With MASH and HFpEF

This Phase 1b multicenter randomized double-blind placebo-controlled study evaluates the safety, tolerability and hepatic pharmacodynamic effects of resmetirom in adults with metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF). Participants are randomized 2:1 to resmetirom or placebo for 24 weeks.

Optimised Cardiovascular and Renal Protection in Patients With Chronic Kidney Disease and Cardiovascular Disease

The goal of this clinical trial is to investigate whether care in a specialised Cardio-Renal Clinic can improve the health of people living with both cardiovascular disease and chronic kidney disease. The clinic brings together expertise in heart and kidney disease and provides structured treatment based on current clinical guidelines. The main research questions are: * After one year, does care in the Cardio-Renal Clinic improve measures of heart and kidney function, quality of life, symptoms, and physical ability compared with usual care? * After five years, does care in the Cardio-Renal Clinic reduce the risk of death, hospitalisation for heart failure, heart attack, stroke, worsening kidney function, or kidney failure compared with usual care? At the beginning of the study, all participants will undergo a detailed assessment of heart and kidney health. This will include blood and urine tests, an ultrasound examination of the heart, questionnaires, and tests of physical ability. Participants will then be randomly assigned to either optimised care in the Cardio-Renal Clinic or usual care. Participants assigned to the Cardio-Renal Clinic will have treatment reviewed and adjusted by a multidisciplinary team. The clinic may recommend or prescribe approved medications that are already used in routine care for heart and kidney disease. No experimental medications will be used. Participants assigned to usual care will continue to receive care from a general practitioner and any hospital departments involved in treatment.

Chronic Exogenous Ketosis in HFpEF

The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Patients with HFpEF often have difficulty exercising, and our goal is to understand whether a ketone drink changes much patients can exercise. The study has three visits, including a baseline visit to assess for study eligibility, and two visits (one after 8 weeks of a ketone drink or a placebo drink, and another one after 8 weeks of whichever drink the participant did not receive the first time).

Changes in Intramyocardial Fat Assessed by Cardiac CT Before and After Bariatric Surgery and Their Relationship With Cardiac Diastolic Function

The goal of this observational study is to learn if weight loss surgery can lower fat inside the heart muscle and improve how the heart relaxes in adults with obesity. The main questions it aims to answer are: Does fat inside the heart muscle decrease after weight loss surgery? Does heart relaxation (diastolic function) improve after surgery? Are changes in heart fat linked to changes in weight, body fat, and blood markers? Participants who are already planning to have weight loss surgery will take part in this study. Participants will: Have a heart CT scan to measure fat in the heart muscle before surgery and about 6 months after surgery Have an ultrasound of the heart (echocardiogram) to check how the heart fills and relaxes Have body composition testing to measure fat and muscle Have blood tests, including routine tests and additional markers related to heart function and metabolism Researchers will compare each participant's results before and after surgery to see if heart fat decreases and if heart function and blood markers improve.

This Will be a Randomized Comparison of the Proteomic Effects of Vicadrostat/Empagliflozin Versus Empagliflozin and Versus Empagliflozin/Spironolactone in Heart Failure Patients With Preserved Ejection Fraction

The SPECTRA-HFpEF Study is a randomized, double-blind, Phase 2 clinical study designed to evaluate and compare the biological effects of vicadrostat in combination with empagliflozin, empagliflozin alone, and spironolactone in combination with empagliflozin in adults with heart failure and preserved ejection fraction. The study will enroll approximately 200 participants with chronic heart failure, New York Heart Association Class II to IV symptoms, and left ventricular ejection fraction greater than 40%. The primary objective is to determine whether treatment with vicadrostat/empagliflozin produces differential changes in circulating plasma proteins compared with spironolactone/empagliflozin, using a broad proteomic panel measured over the course of treatment. These proteomic changes may help identify biological pathways affected by each treatment strategy, including pathways related to inflammation, myocardial fibrosis and remodeling, kidney function, cardiac stress, and aldosterone-related signaling. Participants will complete an approximately 26-week study period, including screening, treatment, and follow-up phases. After screening and any required washout of prior sodium-glucose cotransporter 2 inhibitor therapy, participants will receive open-label empagliflozin and will be randomized in a blinded manner to receive vicadrostat or placebo during the first treatment period. During the second treatment period, participants will receive either continued vicadrostat with empagliflozin or spironolactone with empagliflozin. During the third treatment period, vicadrostat or spironolactone will be discontinued while empagliflozin is continued. Blood and urine samples will be collected at specified visits to evaluate changes in proteomic markers, renin-angiotensin-aldosterone system biomarkers, collagen turnover markers, sex hormone markers, kidney function, proteinuria, inflammatory biomarkers, and cardiac stress biomarkers. Echocardiography and patient-reported health status assessments will also be performed to explore potential effects on cardiac structure, function, symptoms, and quality of life. The study is intended to improve understanding of how aldosterone synthase inhibition with vicadrostat differs from mineralocorticoid receptor antagonism with spironolactone when each is used with empagliflozin in patients with heart failure and preserved ejection fraction. By comparing treatment-related proteomic and biomarker changes across study arms, the study may provide insight into mechanistic differences between these therapeutic approaches and help inform future development of targeted combination therapies for heart failure. Safety and tolerability will be monitored throughout the study through collection of adverse events, serious adverse events, vital signs, electrocardiograms, physical examinations, and clinical laboratory assessments, including kidney function and serum potassium monitoring.

A Study of IBI362 in Subjects With HFpEF or HFmrEF Combined With Obesity

This is a multicenter, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of IBI362 in Chinese subjects with heart failure with ejection fraction retention/mild ejection fraction reduction (HFpEF/HFmrEF) combined with obesity (BMI≥28kg/㎡). This study will enroll about 141 NYHA Class II-III HFpEF/HFmrEF subjects combined with obesity. Eligible participants will be randomly assigned to IBI362 4 mg, IBI362 6 mg, or placebo at a ratio of 1:1:1, randomized by concomitant atrial fibrillation during screening (history/screening ECG). The trial period includes a 2-week screening period, a 52-week double-blind treatment period, and a 4-week safety follow-up period.

Non-Interventional Study of Ferretab® Comp. (Ferrous Fumarate + Folic Acid Prolonged-Release Capsules) Effects in Adult Patients With Iron Deficiency Anemia and Cardiovascular Disease

The goal of this observational study is to learn how well Ferretab® comp. works and how safe it is for adults with iron deficiency anemia and cardiovascular disease who are receiving treatment as part of their usual medical care. The main questions it aims to answer are: * Does treatment with Ferretab® comp. improve anemia? * Does treatment with Ferretab® comp. improve heart-related symptoms, exercise tolerance, and overall well-being? * What side effects do participants have while taking Ferretab® comp.? This is a non-interventional study. Participants will receive Ferretab® comp. because their doctor has already decided to prescribe it as part of routine medical care. Ferretab® comp. is an oral medicine that contains iron (as iron fumarate) and folic acid. The study will not change their treatment. Participants will: * Take Ferretab® comp. for 12 weeks as prescribed by their doctor. * Attend study visits at the start of treatment, after about 4 weeks, and after about 12 weeks. * Have routine blood tests and health assessments during the study. * Report any side effects and record information in a patient diary. * Answer questions about their symptoms, exercise tolerance, and how easy the treatment is to use.

The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

This project is an observational study in patients with heart failure with preserved ejection fraction (HFpEF) who are candidates for treatment with weight loss medication to manage obesity or diabetes as part of their standard clinical care. This study will include multiple experimental visits before and after treatment (minimum 7 percent weight loss, between 9-12 months) to understand how increased adiposity and inflammation effects skeletal muscle and cardiovascular health and function and to examine the effect of medically directed weight loss on skeletal muscle health and exercise tolerance. The objective of this study is to 1. Define the mechanisms by which adiposity impairs exercise hemodynamics, microvascular function, and oxygen transport/utilization in patients with HFpEF. 2. Determine if intensive medically directed weight loss can reduce microvascular inflammation and normalize exercise hemodynamics. 3. Quantify the effect of medically directed weight loss on skeletal muscle function and catabolism. Hypotheses 1. Perfusion of subcutaneous adipose tissue disrupts blood flow distribution and impairs muscle microvascular perfusion and exercise hemodynamics. 2. Extramyocellular muscular lipid deposition and microvascular endothelial inflammation is associated with reduced capillarity and impaired microvascular perfusions, while intramyocellular triglyceride content is associated with poor skeletal muscle oxidative capacity, 3. Intensive weight loss will improve exercise hemodynamics, microvascular perfusion, and reduce muscular inflammation, and resistance training will augment these effects.

Pilot Study of Endoscopic Sleeve Gastroplasty for Obese Patients With Heart Failure and Preserved Ejection Fraction

This is a small research study to see whether losing weight with a minimally invasive weight-loss procedure called endoscopic sleeve gastroplasty (ESG) can help improve symptoms of a type of heart failure called HFpEF in adults with obesity.

PREACTIVE: Preconditioning Exercise Intervention to Improve Symptoms and Quality of Life in Comorbid Atrial Fibrillation and HFpEF

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are very common conditions that often occur together and result in worsening symptoms and reduced quality of life (QoL). Limitations being able to participate in activities of daily living is a primary complaint for AF-HFpEF patients, yet effective strategies to address this issue remain limited. While exercise interventions targeting aerobic training (AT) are recommended for patients with AF and HFpEF, unique challenges exist in this patient population who tend to be older. Specifically, many older patients with AF and HFpEF have muscle weakness, sarcopenia and frailty, that can make aerobic-focused exercise difficult and less tolerable. This study proposes that starting with progressive resistance training (PRT) before aerobic exercise may overcome these issues by improving muscle strength, making AT more manageable, and leading to better health outcomes. The goal of this study is to assess whether a sequential exercise program, named 'PREACTIVE' improves how people feel, decrease the amount of symptoms, and their ability to participate in exercise and activities. This study will specifically test a sequenced exercise approach of resistance training followed by aerobic exercise to improve symptoms, and quality of life in AF-HFpEF.

IRONICA: IRON Repletion In Heart Failure - A Comparison of Oral and IV Approaches

The goal of this clinical trial is to learn which iron treatment works better for adults with congestive heart failure and low iron levels: intravenous (IV) iron given through a vein or oral (PO) iron taken by mouth. Participants must have heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) and a transferrin-saturation (TSAT) level below 20 percent. The main questions the study will answer are: 1. Does IV iron raise walking distance on a 6-minute walk test more than oral iron after 24 weeks? 2. Does IV iron improve symptoms and quality of life more than oral iron? 3. How do the two treatments compare for safety, side effects, and hospital readmissions/ mortality? Researchers will compare IV ferric carboxymaltose with oral ferrous sulfate to see which option helps people feel and function better. What participants will do * Be randomly assigned by (like flipping a coin) to IV iron or oral iron. * Receive either a one-time IV iron infusion (with possible repeat at 12 weeks) or take iron pills twice each day for 24 weeks. * Visit the infusion clinic at 6 weeks for second dose of IV iron if needed. * Visit the clinic at 12 weeks for a follow-up to gather follow-up data including 1. A 6-minute walk test 2. Brief symptom and quality-of-life surveys 3. Blood tests to measure serum iron, ferritin, and transferrin saturation This study will help doctors decide whether IV or oral iron is the safer, more effective way to treat iron deficiency in people with heart failure in our local community.

AI-based Echocardiography for Detection of Cardiac Amyloidosis

Cardiac amyloidosis is characterized by deposition of misfolded protein in the myocardium causing mainly heart failure symptoms with preserved left ventricular ejection fraction. There are also specific clinical (bilateral carpal tunnel syndrome, polyneuropathy, skin bruising, ruptured biceps tendon…), biomarkers (disproportionally elevated NT-proBNP to the degree of heart failure, persistent elevated troponin, proteinuria..), electrocardiographic (reduced voltage of QRS, atrial fibrillation..) and echocardiographic features (concentric left ventricular hypertrophy, dilated atria, reduced global longitudinal strain with typical pattern of apical sparing, diastolic dysfunction…). Early diagnosis of the disease is crucial to identify patients that may benefit from appropriate treatment. Suspected cardiac amyloidosis on echocardiography or on cardiac magnetic resonance needs to prompt the request of serum free-light chain quantification and serum and urine immunofixation as well as single photon emission computed tomography (SPECT) using bone radiotracers. Echocardiography is the imaging technique of first choice to evaluate patients with dyspnea complaints and suspected heart failure as well as other pathologies. Echocardiography is a technique of first choice to evaluate patients with cardiovascular risk factors such as arterial hypertension and diabetes and many of those patients may have echocardiographic features that can be observed in early phases of cardiac amyloidosis. Currently, identification of patients with cardiac amyloidosis with available echocardiographic tools remains challenging. However, novel artificial intelligence (AI)-based algorithms applied to echocardiographic images for analysis may help the cardiologists in the identification of early phase of cardiac amyloidosis. Early diagnosis of cardiac amyloidosis is key to implement effective therapies that have demonstrated to improve survival. Several studies have demonstrated the accuracy of AI-based algorithms applied to echocardiography for the diagnosis of cardiac amyloidosis. The hypothesis of the present prospective study is to evaluate the accuracy of the AI-based algorithm to identify patients with echocardiographic findings suggestive of cardiac ATTR amyloidosis using as ground truth the subsequent analysis with imaging techniques that permit its diagnosis such as 99mTc-pyrophosphate (PYP) SPECT and cardiac magnetic resonance as well as hematologic tests. If needed, histological confirmation on cardiac or extracardiac tissue could be performed, as recommended by recent consensus document from the Heart Failure Association of the European Society of Cardiology. In addition, this study will help to answer the true prevalence of ATTR cardiac amyloidosis among patients referred to transthoracic echocardiography that present red flags for ATTR cardiac amyloidosis. The AI-based algorithm is the software Us2.ai which has been used in other populations for this purpose, as previously published.

HFpEF Phenotyping With Echo, Clinical, and Biomarkers

The EPIC-HFpEF registry is a nationwide Italian study that follows people with a specific type of heart failure called HFpEF. About 500 patients will be enrolled from several specialized hospitals and monitored for up to two years, without changing their usual treatment. The goal is to better understand this complex condition by identifying different patient "types" based on clinical features, heart imaging, and blood markers. Researchers will also look at how these groups are treated in real life and how their disease progresses over time. By doing this, the study aims to improve how doctors classify and manage HFpEF, moving toward more personalized and effective care for patients in the future.

Hearts on Fire: Targeting Inflammation in Heart Failure With Preserved Ejection Fraction

Subjects undergo a gadolinium-based CMR followed by an iron infusion and then a repeat CMR in 72 hours

Fecal Microbiota Transplantation for Elderly Patients With HFpEF: A Randomized Controlled Trial

This is a single-center, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in elderly patients with heart failure with preserved ejection fraction (HFpEF). HFpEF is a common type of heart failure in older adults, often associated with poor quality of life and frequent hospitalizations. Recent research suggests that changes in gut bacteria may contribute to the progression of HFpEF. FMT aims to restore a healthy gut microbiome, which may improve heart function and reduce symptoms. Participants will be randomly assigned to receive either FMT or a placebo treatment. The primary goal is to compare changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score between the two groups at 20 weeks. Secondary goals include assessing improvements in exercise capacity (6-minute walk test), NYHA functional class, and safety outcomes. The study will enroll 50 elderly patients (aged ≥60 years) with confirmed HFpEF. All participants will receive standard medical care for HFpEF throughout the study. This trial is sponsored by The First Affiliated Hospital of Air Force Medical University and conducted in accordance with ethical standards.

The Effect of Sacubitril and Valsartan on Heart Function in Chronic Hemodialysis Patients With HFpEF

Heart failure is the most common cause of death of patients on chronic hemodialysis treatment, and to date there is no effective therapy for the treatment of this comorbidity in this group of patients. The most common form of heart failure in these groups of patients is heart failure with preserved ejection fraction (HFpEF). As a new therapy for heart failure, a new group of drugs called angiotensin receptor and neprilysin inhibitors (ARNI) has been imposed, whose representative is the drug sacubitril/valsartan. The therapy has been shown to be superior to any other therapy to date for the treatment of heart failure with reduced ejection fraction (HFrEF) and has been included in European and American guidelines for the treatment of patients with HFrEF. Since 2022, the drug has been approved in the USA for the treatment of patients with HFpEF, while in Europe it is still not approved for this indication. Currently, the drug is not approved for patients on chronic hemodialysis anywhere in the world, and its effect on this group of patients is unknown. There are very few studies examining the safety and efficacy of sacubitril/valsartan in chronic hemodialysis patients with HFpEF. Precisely because of this, the aim of this study is to determine the effectiveness of this drug in these groups of patients. I will conduct the research as a randomized controlled trial (single blind research) where the subjects will be patients on chronic hemodialysis treatment who have proven HFpEF. HFpEF is proven by the HFA-PEFF scale. The patients will be divided into two groups - the test group and the control group (30 patients in each group). The input variables will be patients on chronic hemodialysis treatment (whose hemodialysis treatment lasts at least one year); patients with heart failure with preserved ejection fraction; height; weight. Output variables will be heart ultrasound parameters and laboratory findings (NTproBNP, hs troponin, aldosterone, renin). The aim of the study is to determine the effect of sacubitril/valsartan on ultrasound parameters and on cardiovascular and other biomarkers in patients on chronic hemodialysis treatment with HFpEF.

Coronary Artery Stents in Heart Failure With Preserved Ejection Fraction

HFpEF (heart failure with preserved ejection fraction) is a condition in which the heart muscle becomes stiff and can't pump blood properly. People living with HFpEF also often have coronary artery disease, where the blood vessels that supply the heart are narrowed or blocked. It is not yet know whether opening these arteries with stents improves symptoms or quality of life with HFpEF. REPRIEVED is a randomised clinical trial that aims to find out if heart stents can improve quality of life for people living with heart failure with preserved ejection fraction (HFpEF) and coronary artery disease. Researchers will compare two groups of people; those who have a stent procedure to those who have a placebo procedure. The placebo procedure feels the same as a stent procedure but does not include a stent. 350 people with HFpEF and coronary artery disease will be asked to take part. Participants will be monitored over a period of 6 months to see if and how quality of life changes. Before the procedure, participants will be asked to complete a short health questionnaire, have a blood test, undergo an electrocardiogram (heart tracing) and scans of their heart. On the day of the procedure, the participant will come to the hospital for an angiogram and will be randomly allocated to have either treatment with a stent or the placebo procedure without a stent. Participants will not know whether they have received heart stents. This helps researchers know that any improvements in their quality of life are not just related to how they feel about the stenting treatment. Participants will then be contacted by a member of the research team at 3 months and 6 months after their procedure. At 3 months, participants will complete a short health questionnaire either by phone or during a hospital visit. At 6 months, participants will attend the hospital to complete a short health questionnaire, have blood tests, a scan of the heart (echocardiogram) and an electrocardiogram (heart tracing) to measure any changes in the heart. Participants will be told whether they received the stent procedure or the placebo procedure.

The Role of Epicardial Adiposity in Heart Failure With Preserved Ejection Fraction

In this study the investigators are aiming to recruit 130 patients with heart failure with preserved ejection fraction who are obese and non-obese to undergo CT and MRI scans, as well as some other investigations including blood tests, to help investigate if having more fat around the heart leads to worse heart function in this condition. This may lead to the development of new treatments aimed at lowering fat levels around the heart and in the rest of the body, specifically to treat HFpEF.

Determination of the Prevalence of Unrecognized Heart Failure Among Patients at Risk in Urban Areas Across Germany Using CMR

Heart failure (HF) in patients at risk is often overlooked, and when detected, there is a lack of early and effective preventive interventions. The WE-CARE-HF-CMR study, conducted in large cities/metropol areas in Germany ( \> 1.000.000 inhabitants), aims to close this gap by evaluating the feasibility of a mobile, telemedicinemonitored HF-screening approach combining cardiac magnetic resonance imaging (CMR), quality of life assessment and laboratory tests as key elements in asymptomatic patients at risk. WE-CARE-HF-CMR will provide a proposal for a comprehensive, contemporary screening approach for patients at risk to develop HF tailored to the needs of the target population. This will provide important new information on the prevalence of asymptomatic HF in at-risk patients in urban versus rural areas. The results of the study will be compared with the results from the "HERZCheck'' trial, which provides data from approximately 4,500 participants in rural areas in Germany and has already been completed (NCT05122793).

CAPTURE-HFpEF: National Study of Identification and Phenotyping of Heart Failure With Preserved Ejection Fraction

The goal of this observational study is to improve early detection, characterization, and understanding of heart failure with preserved ejection fraction (HFpEF) in adults at risk of or diagnosed with HFpEF, including men and women across Danish regions. The main questions to answer are: Can systematic cardiovascular screening and deep phenotyping improve early identification and classification of HFpEF? Which clinical, imaging, biomarker, and metabolic characteristics define subtypes (phenotypes) of HFpEF and predict disease progression and outcomes? Researchers will compare participants with HFpEF, participants at risk of HFpEF, and relevant control groups to see if differences in biomarkers, imaging findings, and clinical characteristics can identify early disease stages and distinct HFpEF phenotypes. Participants identified with HFpEF will: * Undergo detailed cardiovascular examinations (e.g., echocardiography, CT and other imaging examinations, RHC, CPET) * Provide blood and tissue samples for biomarker and metabolic analyses * Complete clinical assessments and questionnaires * Have relevant health data collected from national health registries * Attend follow-up assessments to monitor disease progression