Clinical Research Directory

Oral Branched-chain Amino Acid Supplementation for Cirrhotic Patients With Sarcopenia

The goal of this clinical trial is to compare the nutritional parameters after 24-week supplementation of branched-chain amino acids in cirrhotic patients with low muscle mass. The main questions it aims to answer are: Is there the differences in the proportions of cirrhotic patients recovering from low muscle mass at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there the differences in the change of skeletal muscle index (SMI) measured by abdominal computed tomography (CT) at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in other indices related to low muscle mass, including appendicular skeletal muscle mass (ASM), ASM/height\^2, handgrip strength, and 6-meter walk speed at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in the liver frailty index (LFI), consisting of handgrip strength, chair stands, and balance, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in serum albumin levels, at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Is there changes in severity of liver disease, including the Model for End-Stage Liver Disease-Sodium Score (MELD-Na score), Child-Turcotte-Pugh score, and liver stiffness measured by transient elastography at 24 weeks among cirrhotic patients with low muscle mass who received BCAA supplementation and the placebo group? Participants will be asked to do following tasks: Participants will be asked for basic information such as age, place of residence, and contact phone number. Participants will undergo measurements of body weight, height, body mass index (BMI), muscle mass, and body fat content using a body composition analyzer, a total of 2 times (at the beginning and end of the research), and an upper abdominal computed tomography (CT) scan without additional radiation exposure, only once (at the end of the research) throughout the study. Participants will be tested for muscle function, including handgrip strength, a 6-meter walk test, chair stands, and balance, all performed twice (at the beginning and end of the research). Laboratory testing will include a complete blood count, liver and kidney function, blood clotting function, mineral levels, cholesterol, and glucose. Blood will be drawn a total of 2 times (at the beginning and end of the research) during the study, with each blood draw approximately 15 milliliters (1 tablespoon). Transient elastography will be performed twice (at the beginning and end of the research) during the study, with each Transient elastography taking approximately 10 minutes. Participants will be randomly assigned to either the group receiving branched chain amino acid (BCAA) medication or the placebo group, and you will take the assigned medication twice daily for a total of 24 weeks. Participants will receive dietary and exercise recommendations from the research team and nutritionists in a group format, taking approximately 1 hour. Participants will have follow-up appointments to monitor your condition three times during the study, at weeks 4, 12, and 24. These appointments will include inquiries about side effects from medication and placebo use, exercise, and dietary intake, each lasting approximately 30 minutes. Participants will be asked to take photos of your daily meals for 3 days before meeting with the physician at weeks 4 and 12, to provide data for assessing your calorie intake. Participants can send these meal images via the online application, prepared by our research team. If participants are unable to do so, participants will be asked to keep a food diary and report your food and portion sizes to the research team.

Abbreviated Magnetic Resonance Imaging vs Ultrasound Surveillance for Liver Cancer dETection in People at High Risk of Developing Liver Cancer

Aim: To use magnetic resonance imaging (MRI) scans without contrast to help improve diagnosis of liver cancer in people who are at increased risk of developing liver cancer. Background: People with any condition that affects the liver over a long period of time can develop cirrhosis. Conditions and risk factors that can lead to cirrhosis include alcohol excess, liver steatosis (lipid or fat accumulation in the liver) and infection with the viruses hepatitis B and C. One of the concerns about people with cirrhosis is that they are at increased risk of developing liver cancer. People with cirrhosis are recommended to have an ultrasound scan (USS) every 6 months (surveillance for liver cancer) so that if a cancer develops, it is diagnosed at an early stage when it can be cured. However, ultrasound can miss cancers even in people having scans every 6 months. Furthermore, the risk of cancer is not alike among people with cirrhosis. For example, people with more advanced cirrhosis and those with cirrhosis from hepatitis B are at higher risk. It is therefore possible that better tests than ultrasound are needed for people with cirrhosis who are at particularly high risk of developing cancer. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) scans with dye injection (contrast) are used for liver cancer diagnosis. However, they cannot be done every 6 months because of costs, capacity and toxicity from high CT radiation doses, and MRI contrast build-up in the brain with repeated MRI contrast injections. MRI scans without contrast are not toxic, could be done in 20 minutes and are cheaper, so could be done every 6 months. In the experience of the study investigators, MRI without contrast may raise suspicion of liver cancer in cases missed by ultrasound, so it could be used for surveillance instead of ultrasound. This study aims to find out if it is feasible to use a quick MRI (20 minutes) without contrast as surveillance for liver cancer in people at high risk of liver cancer due to liver cirrhosis and to compare this MRI with ultrasound. Design and Methods: The investigators will recruit 300 people at higher risk of developing liver cancer because of cirrhosis. Study participants will have an ultrasound scan every 6 months as they would in their standard clinical care and an additional 6 monthly non-contrast MRI scan for 30 months (6 visits). If the ultrasound or non-contrast MRI raises concern for a possible liver cancer, an MRI scan with contrast (with dye injection) will be done for definitive diagnosis. All participants will have an MRI with contrast at the end of 30 months (M30) to ensure that no cancers were missed. Participants will be asked to complete questionnaires to measure quality of life, anxiety, and their experience of MRI and ultrasound scans and data will be collected from their medical notes. The number of liver cancers detected by ultrasound will be compared to the number detected by the non-contrast MRI scans.

Optimized Remission in Alcohol-related Liver Cirrhosis

The incidence of liver cirrhosis is increased fivefold for men and tripled for women in the last forty years. The clinical course of liver cirrhosis includes complications of ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and infections that markedly worsen prognosis. These complications are driven by the development of portal hypertension in the liver. This progression to the 'decompensated' stage is considered a hallmark in the disease course, as the decompensation is associated with a markedly increased risk of further complications and death. Increasing evidence indicate that active measures of treatment of the underlying cause of liver disease and removal of the toxic agents causing cirrhosis may slow disease progression or even induce regression of cirrhosis. This concept is described as hepatic recompensation. There is a need for clinical studies investigating novel biomarkers with the capability to predict and monitor improvement in alcohol related liver cirrhosis, Between 75% and 80% of patients with liver cirrhosis in Denmark have or have had a harmful use of alcohol. Alcohol related liver disease (ArLD) has a major impact on patients' health and lives, and there is an unmet need to investigate treatment options that not only relieves complications, but also address the underlying pathways of alcohol related liver disease, also in severe stages of alcohol related cirrhosis (ALC). Factors such as BMI, female gender and mild portal hypertension are known to be associated with an increased likelihood of recompensation. Additional factors of genetic activation and molecular biomarkers from the proteome and lipidome have only attracted minor attention, and the impact of treating the drivers of decompensation, portal hypertension and alcohol use, and their impact on the natural cause of disease, have not been addressed. The molecular pathophysiology of ArLD is incompletely understood. Characterization of the proteome dynamics across the spectrum of ALD could provide new insights into disease mechanisms of both progression and remission of disease. Several markers of inflammation and cytokines are involved in driving decompensation and has the potential to predict the risk of early death. It is unknown whether such markers can predict remission and recompensation in ALC and AH. Prospective studies investigating the associations between biomarkers of metabolism and prognosis, monitoring and efficacy og treatment in ALC are missing. The overall objective of the present study is to investigate the molecular profile and pathways in persons with ALD to support personalized monitoring and follow-up in liver cirrhosis. The study is an incidence cohort in which patients will be followed from diagnosis to death or withdrawal from the cohort. We will seek to include patients consecutively within three months of diagnosis. All patients with a debut of alcohol related liver cirrhosis during admission regardless of the reason for admission, are eligible for inclusion. All participants in this study will be offered the standard of care treatment. Alcohol cessation intervention including medical treatment of withdrawal symptoms and craving, referral to municipal offers of alcohol treatment, and motivational interviews is part of the treatment. The study will contribute to a better characterization of advanced liver disease related to alcohol and contribute to an improved future organization of treatment- and rehabilitation offers to patients with liver disease. thorough characterization and consecutive inclusion will enhance our understanding on the incidence, prevalence and impact of ALC in the population, as well as the utilization of health care resources allocated to its treatment. A deeper insight into the molecular mechanisms of liver progression and remission will, in combination with clinical data, support our ability to predict outcomes in cirrhosis, facilitate personalized monitoring aiming at providing the right treatment for the right patient at the right time.