Cachexia

Study to investigate the efficacy, safety and tolerability of systemic chemotherapy plus ponsegromab versus systemic chemotherapy plus placebo for the first-line treatment in adult participants with cachexia and metastatic pancreatic ductal adenocardinoma.

Study to investigate the effect of ponsegromab on skeletal muscle mass and physical function in adult participants with non-small cell lung cancer associated cachexia.

The purpose of this clinical trial is to evaluate the safety and tolerability of SXRN Plasmid DNA Technique in patients with advanced solid tumors.

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.

Primary Objective: To evaluate the effect of nanocrystalline megestrol acetate versus placebo on body weight and appetite in patients with unresectable hepatocellular carcinoma receiving TACE combined with targeted and immunotherapy.Secondary Objectives: To evaluate the effect of nanocrystalline megestrol acetate versus placebo on quality of life, inflammatory markers, nutritional indicators, and psychological stress in patients with unresectable hepatocellular carcinoma receiving TACE combined with targeted and immunotherapy.Exploratory Objective: To explore the impact of nanocrystalline megestrol acetate versus placebo on survival benefit in patients with unresectable hepatocellular carcinoma receiving TACE combined with targeted and immunotherapy.

Cervical cancer, ranking as the fourth most prevalent malignancy in women globally, presents significant challenges in nutritional management. Approximately 31% of patients develop cancer-related malnutrition/cachexia, with 10-20% of deaths directly attributable to nutritional depletion. The disease process and its treatment - particularly concurrent chemoradiotherapy (CCRT) - create a destructive cycle through multiple mechanisms. Tumor-derived factors (including activins and myostatin) and inflammatory cytokines (such as TNF-α and IL-6) actively promote muscle and fat catabolism. CCRT toxicity, especially from platinum-based drugs, worsens this condition by inducing mitochondrial dysfunction and accelerating protein degradation, leading to clinically significant sarcopenia. This metabolic disruption has dire consequences, with studies showing severe weight loss during CCRT correlating with a 2.37-fold increase in mortality risk (HR 2.37, p=0.036). Nanocrystalline megestrol acetate (MA) emerges as a promising therapeutic intervention with dual mechanisms of action. Centrally, it modulates D2 receptors to upregulate neuropeptide Y (NPY), effectively stimulating appetite. Peripherally, it suppresses key inflammatory cytokines (IL-6 and TNF-α), thereby reducing systemic inflammation and muscle wasting. Its efficacy is well-established, with endorsement from major oncology guidelines (ASCO, NCCN, ESMO) for cancer cachexia management. A comprehensive meta-analysis of 35 clinical trials involving 4,234 patients demonstrated MA's superiority over placebo, showing significant improvements in appetite (RR 2.2), weight gain (RR 1.6), and quality of life (RR 1.8). The nanocrystalline formulation represents a substantial pharmacological advancement over conventional MA. While traditional preparations have limited solubility (2 µg/mL) and require high-fat meals for adequate absorption, the nanocrystalline version (with particles reduced to 26.6 nm) demonstrates 22% greater bioavailability. This translates to clinically meaningful differences: fasting-state peak concentrations increase from 187 ng/mL to 1,133 ng/mL, the time to observable effect shortens from 14 days to just 3 days, and 12-week weight gain improves from 3.5 kg to 5.4 kg (with 40% being lean mass). Dose optimization studies confirm 800 mg/day as the optimal conventional MA dose, with the nanocrystalline equivalent being 625 mg/day due to its enhanced bioavailability. The proposed clinical investigation will evaluate this intervention in FIGO IB3-IVA cervical cancer patients (n=5) undergoing CCRT. The study employs a two-arm design comparing nanocrystalline MA (625 mg/day) plus CCRT against CCRT alone. Primary endpoints focus on BMI changes at 8 weeks, with secondary assessments of nutritional status, inflammatory markers, and quality of life measures. This research aims to establish nanocrystalline MA as a means to break the cachexia cycle in cervical cancer treatment, potentially improving both treatment tolerance and survival outcomes.

A study to evaluate the safety, tolerability, and preliminary efficacy of DS010 in patients with cancer and cachexia

A major complication of pancreatic adenocarcinoma (PDAC) is cancer cachexia (CC) which is a complex syndrome characterized by skeletal muscle mass loss (with or without loss of fat mass) and progressive functional impairment not reversible by conventional nutritional support. It is estimated to occur in over 75% of patients with advanced PDAC, the highest incidence of all solid tumors, and contributes significantly to poor outcomes and mortality. Though there is overlap amongst the pathophysiologic studies evaluating CC in murine models of different tumor types, the high prevalence of CC within gastrointestinal (GI) malignancies and specifically PDAC suggest that dedicated studies evaluating polymorphisms in candidate genes specific to PDAC warrant further evaluation. The collection and analysis of specimens under this study will facilitate the identification and characterization of genomic polymorphisms associated with CC in PDAC patients. Subsequently, this data may help contribute towards diagnostic and therapeutic treatments that may improve patient outcomes.

This study is a prospective, randomized, parallel-controlled clinical trial. The primary objective is to evaluate the superiority and safety of nanocrystalline megestrol acetate in combination with standard therapy compared with standard therapy alone in improving appetite and body mass index (BMI) during treatment in patients with early-stage or locally advanced hepatocellular carcinoma at the cachexia stage.

This open label ascending dose study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AV-380 in cancer patients with Cachexia. AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.

Some people with cancer suffer from muscle wasting, lose weight and feel tired. This process, termed cachexia, is a significant problem and can lead to a reduction in both quality and quantity of life. Cachexia is caused by interactions between the tumour and the patient. Historically, it was considered to be a purely end-stage phenomenon of advanced cancer, however, it is now known that early signs of cachexia can even influence the outcomes of patients with potentially curative pathology, including those planned for a surgical resection. This study aims to collect information, from patients who are at risk of cachexia, about body composition, physical activity, quality of life and the body's immune response to cancer. Previously these measures have been most frequently studied in isolation, or at one single time-point, and are therefore likely to give an incomplete picture. A more holistic characterisation of surgical patients at risk of cancer cachexia, across their treatments, is currently lacking. Participants with cancer will be recruited to the study from surgical services in the United Kingdom (UK). A small number of 'control' patients without cancer, who are undergoing surgery for a benign condition, will also be recruited for comparison. Those recruited will have their height and weight measured, answer questionnaires about quality of life, undergo assessment of their physical function and levels of activity, have blood taken to analyse markers of inflammation and have their body composition measured by a variety of methods. A subgroup of patients will also undergo an additional magnetic resonance imaging (MRI) scan of their abdomen and thighs. At the time of their operation, participants will also have small biopsies of muscle, fat, tumour and urine taken for biochemical analysis. Patients with cancer, will be asked to return for three follow up appointments during the year after their operation where these assessments will be repeated.

Evaluation of the effects of body composition, psychosocial factors, and drug-related problems on clinical progression (such as toxicity, treatment response, and quality of life) in cancer patients treated with immune checkpoint inhibitors

Rationale: One of the greatest challenges in the field of cancer treatment is cachexia, a multifactorial syndrome characterized by substantial loss of body weight (muscle and fat mass), leading to progressive functional impairment. Cancer cachexia significantly impairs quality of life and survival as well as treatment outcome. Despite its considerable relevance for the prognosis of cancer patients, the diagnosis of cachexia is problematic. The current consensus definition of cancer cachexia is based on weight loss over the last six months. In practice, this is assessed by subjective reporting by the patient, which is subject to error and bias. Novel technologies enable accurate, standardized, and objective assessment of body weight and physical activity by newly diagnosed cancer patients in the home situation. Because of the increasing implementation of neo-adjuvant treatment strategies that offer an extended time-window for the collection of these data, there is a great opportunity to use this information in risk analyses by treating physicians, optimization of pre-habilitation programs, and in the shared-decision making process with the patient. Objective: The central aim of the 'Patient-Recorded Indexing MeasurementS' (PRIMS) study is to improve the accuracy of the diagnosis of cachexia in patients with cancer. This aim will be achieved by focusing on two objectives. The primary objectives are to compare self-reported and objectively measured pre-treatment weight change. The secondary objectives are to define host phenotypes and to investigate longitudinal associations between body weight and physical activity patterns. Study design: Explorative pilot study Study population: Patients ≥18 years old undergoing curative-intent chemotherapy or surgery for cancer. Patients will be included in two referral centers specialized in treatment of patients with upper gastrointestinal, hepatobiliary, pancreatic, colorectal, and ovarian cancer. Main study parameters/endpoints: The primary endpoint is body weight change over time. Objectively measured body weight will be compared to subjectively reported body weight change. Their respective association with treatment-related adverse events and survival will be investigated. Survival will be calculated from date of start of treatment until death. Chemotherapy related adverse event will be recorded using the Common Terminology Criteria for Adverse Events. Postoperative adverse events will be scored according to the Clavien-Dindo classification. Secondary endpoints: The secondary endpoints will be the association between other cachexia-related parameters that are investigated in the study and adverse events / survival. Other parameters include physical activity over time, using accelerometry, baseline physical assessment, anthropometric measurements, body composition, and laboratory results. Besides this, other endpoints that will be assessed are disease-free survival (calculated from the first day of treatment until first recurrence) and response to chemotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

This lay description has been written in conjunction with, and the content approved by our Patient and Public Involvement collaborators. Patients with kidney cachexia will experience extreme muscle loss, reduced strength and symptoms including fatigue, reduced appetite and lower quality of life. Patients are also at an increased risk of hospitalisation and shortened life expectancy. Previous research suggests that treatments that target several causes of the muscle wasting syndrome (known as cachexia), show better outcomes for patients than treatments using just one method (for example only exercise). We want to see if combining different treatments (exercise, dietary advice and anti-inflammatory supplements) will improve outcomes for patients with kidney failure receiving haemodialysis at risk of developing kidney cachexia, compared to patients who only receive routine kidney care alone. However, there is currently no routine treatment for kidney cachexia. Individual treatments, such as exercise, have not been successful to slow the progression of wasting in chronic diseases. Our recent review of scientific literature highlighted dual treatments of exercise and dietary advice is effective to varying degrees. Combined treatments which include anti-inflammatory supplements (including those found in fish oils), alongside exercise and dietary advice, have been successfully trialled in other chronic illnesses, such as cancer for the treatment of cachexia. However, this bundle of three treatments has not been tested in patients with kidney cachexia. It is important to test whether such a combination of treatments will be practical for patients and clinicians. Our study will assess how well this intervention works in the healthcare system and if it shows potential to help patients with kidney cachexia. Patients at risk of kidney cachexia who are receiving haemodialysis at two renal departments have been assigned to the treatment group (Multi-Modal Integrated intervention combining Exercise, Anti-inflammatory \& Dietary advice plus routine care) and two have been assigned to the control group (routine care). Over 12 weeks, those in the treatment group will receive an individualised exercise programme, dietary advice and anti-inflammatory (fish oil) nutritional supplements. We will collect data on how successful the trial is (e.g., how many patients took part, completed all components of the study). Additionally, we will collect data on physical functioning, muscle mass, body weight, quality of life and survival. After 12 weeks, we will interview patients and clinicians to evaluate, if any, changes can be made to improve the intervention within what is called a 'process evaluation'.

This is a multicenter, double-blind randomized controlled clinical study designed to evaluate the efficacy and safety of oral nutritional supplements (ONS) containing levocarnitine for cachexia in lung cancer patients scheduled for or undergoing chemotherapy. Study Design: Recruitment: Approximately 126 pathologically confirmed patients meeting the inclusion criteria will be enrolled across four hospitals (Army Characteristic Medical Center, Chongqing Fifth People's Hospital, Chongqing Thirteenth People's Hospital, and Chongqing Qianjiang District Central Hospital). The planned enrollment is 60 patients at Army Characteristic Medical Center, 22 at Chongqing Fifth People's Hospital, 22 at Chongqing Thirteenth People's Hospital, and 22 at Chongqing Qianjiang District Central Hospital. Randomization: Patients will be randomly assigned in a 1:1 ratio to the control group (63 patients) or the intervention group (63 patients). Interventions: Control Group: Receive 500 mL of enteral nutrition solution daily for 12 weeks (84 days). Intervention Group: Receive 500 mL of enteral nutrition solution containing 4 g of levocarnitine daily for 12 weeks (84 days). Evaluations: Efficacy Assessments: Body composition analysis and other evaluations will be conducted at baseline and after ONS treatment with levocarnitine to assess the effectiveness of the intervention. Safety Assessments: Safety events during the levocarnitine-containing ONS treatment period and within 28 days after neoadjuvant therapy will be collected to evaluate treatment safety. Follow-up: After chemotherapy, the investigator will determine the optimal adjuvant treatment and follow-up protocols to assess recurrence and survival outcomes.

Cachexia is common in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Cachexia is a complex syndrome, in which inflammation and retention of uremic toxins are two main contributing factors. In this context, the role of the gut microbiome in CKD cachexia and the potential benefit of increasing the dialysis dose have been poorly explored. Here the investigators propose to study the links between cachexia and the gut microbiome, in association with inflammation and uremic toxins, in dialysis. The specific objectives are the followings: 1. Set up a prospective cohort of deeply characterized kidney failure patients treated with hemodialysis (in-center, self-care dialysis in a satellite unit and at home) and peritoneal dialysis, including evaluation of cachexia, body composition, collection of feces and blood to characterize the gut microbiota, measure serum levels of uremic toxins and inflammatory markers, with a longitudinal follow-up. 2. To compare cachectic versus non-cachectic dialysis patients in terms of gut microbiota, inflammatory markers, level of uremic toxins, muscle transcriptome, dialysis dose and modality. In a subgroup analysis, the investigators plan to compare the different techniques of dialysis (in-center vs home-hemodialysis vs peritoneal dialysis).

This study is a prospective, observational clinical study aimed at evaluating the efficacy of Megestrol Acetate for cachexia in patients with advanced digestive system tumors receiving TKI-based therapy.

Frailty is a geriatric syndrome that primarily affects older patients, but also patients with severe illnesses. It is particularly common among oncology patients, but also among patients with gastrointestinal diseases such as liver cirrhosis or pancreatitis. Sarcopenia, a form of frailty, is defined as a loss of muscle quantity, quality and function. Currently, complex methods such as CT or bioimpedance measurement are available. However, simpler techniques such as ultrasound-based measurement could be alternatives, but still require further validation. In addition, serological muscle markers could support and simplify diagnostics. The aim of this project is to be able to estimate the prognosis of patients at an early stage by measuring sarcopenia using ultrasound and biomarkers.

This monocentric study aims at evaluating the effects of fecal microbiota transplantation from newly diagnosed cachectic and non-cachectic pancreatic cancer patients, and healthy volunteers on several cachexia-related parameters of germ-free mice.

Cancer anorexia-cachexia syndrome is one of the common conditions in cancer patients. Olanzapine has been demonstrated to reduce chemotherapy-induced anorexia. However, there is scarce information regarding olanzapine as a treatment of cancer anorexia among patients who does not receive chemotherapy. Therefore, this randomized controlled trial aims to evaluate the efficacy of olanzapine to lessen cancer cachexia-anorexia syndrome.

The goal of this observational study is to to look for changes within the brain, and changes in body-to-brain signals in people with cancer and people who do not have cancer. The main questions it aims to answer are: 1. Are there differences in areas of the brain known to be related to appetite control, food reward and motivation, between participants with cancer related weight loss and healthy volunteers 2. Do responses to questionnaires and computer based tasks suggest participants with cancer related weight loss have reduced appetite and reduced motivation to eat compared to healthy volunteers, and if so, do questionnaires suggest that this is associated with any other symptoms? Researchers will compare the structure and blood flow in relevant areas of the brain using MRI images between participants with cancer related weight loss and healthy volunteers. Participants will complete questionnaires and computer based tasks to allow researchers to assess areas of the brain which become more active in response to different stimuli. Some computer based tasks will be performed during the MRI scan. This is called functional MRI. A further objective is to obtain an archive of blood samples which will be stored securely for future analysis if relevant hormones or analytes are identified that may be relevant to metabolism or body composition

The aim of the study is to provide information on the interaction between socioeconomic factors, daily physical activity, nutrition and lifestyle on loss of muscle mass and muscle function in patients with heart failure.

The aim of this single-arm prospective, multicenter, cross-sectional study is to evaluate the nutritional status and body composition on tumor regression grade with bioelectrical impedance analysis in gastric cancer patients undergoing multimodal treatment. Results of this study will reveal whether nutritional status and body composition assessment based on bioelectrical impedance analysis will become a validated and objective tool to support clinical decisions in gastric cancer patients undergoing multimodal treatment.

The aim of the study is to evaluate the effectiveness of a multifactorial education and support program for the prevention of cancer-related cachexia syndrome, for patients and their family caregivers during anti-cancer treatment.

Muscle mass loss is a common adverse effect of cancer. Muscle mass loss occurs with or without reduction in body weight. Cancer cachexia (CC) is the involuntary loss of body weight of \>5% within 6 months and it occurs in 50-80% of patients with metastatic cancer. It is estimated that CC is a direct cause of up to 30% of all cancer-related deaths. No treatment currently is available to prevent CC, likely because the chemical reactions that causes of this devastating phenomenon in unknown. No treatment currently is available to prevent muscle mass loss in patients with cancer but is urgently needed as the reduced muscle mass and function is associated with impaired physical function, reduced tolerance to anticancer therapy, poor quality of life (QoL), and reduced survival. There is evidence of an interdependence between informal caregiver (e.g. spouse) and patient QoL. Thus, identifying caregiver distress and needs can potentially benefit QoL for patients with cancer cachexia. Despite the enormous impact on disease outcomes, it is not known why the loss of muscle mass and function occurs and very few studies have investigated the underlying molecular causes in humans. In particular, there is a severe lack of studies that have obtained human skeletal muscle and adipose tissue sample material. Such reference sample materials will be invaluable to obtaining in-depth molecular information about the underlying molecular causes of the involuntary but common muscle mass and fat mass loss in cancer. At a whole body level, cancer cachexia is associated with reduced sensitivity to the hormone insulin, high levels of lipids in the blood, and inflammation. Within the skeletal muscle, the muscle mass loss is associated with elevated protein breakdown and reduced protein build-up while emerging, yet, limited data also suggest malfunction of the power plants of the cells called mitochondrions. The role of malnutrition and how it contributes to weight loss is understood only to the extent of the observed loss of appetite and the reduced food intake because of pain, nausea, candidiasis of the mouth, and breathlessness. Evidence is increasing that the environment of the intestinal system could be implicated in cancer cachexia, yet, the possible effect of cancer and the cancer treatment on the intestinal environment is not understood. Thus, large and as yet poorly understood details of this syndrome precede a later weight loss. Exercise training could help restore muscle function and how the chemical reactions works in cancer. In healthy people, and patients with diabetes, cardiovascular disease, and obesity exercise potently improves health. Exercise has been thought to slow down the unwanted effects of cancer cachexia by changing the reactions mentioned above. Thus, there is a tremendous gap in our knowledge of how and if exercise can restore the cells power plants function, muscle mass, strength, and hormone sensitivity in human cachexic skeletal muscle. Tackling that problem and examining potential mechanisms, will enable us to harness the benefits of exercise for optimizing the treatment of patients with cancer. The data will provide novel clinical knowledge on cachexia in cancer and therefore addressing a fundamental societal problem. Three specific aims will be addressed in corresponding work packages (WPs): * investigate the involvement of hormone sensitivity of insulin and measure the chemical reactions between the cells in patients with lung cancer (NSCLC) and describe the physical performance and measure amount of e.g. muscles and adipose tissue across the 1st type of cancer treatment and understand how that is related to the disease and how patients and informal caregiver feel (WP1). * find changes in the chemical reactions in skeletal muscle, adipose tissue (AT), and blood samples in these patients, to understand how to predict how the disease will develop (WP2). * measure changes of skeletal muscle tissue in response to exercise and see if it might reverse the hormone insensitivity and improve muscle signaling and function (WP3). The investigators believe that: * the majority of patients with advanced lung cancer, at the time of diagnosis already are in a cachectic state, where they lose appetite, and have hormonal changes, and an overall altered chemical actions between the cells affecting both muscle mass and AT. The investigators propose that all this can predict how the disease will progress, and how patient- and informal caregiver fell and how they rate their quality of life. * lung cancer and the treatment thereof is linked with changes in the blood, the muscle tissues, and the adipose tissues, especially in patients experiencing cachexia, that could be targeted to develop new treatment. * exercise can restore the muscles and improve insulin sensitivity and improve the function of the cells power plants in patients with lung cancer-associated muscle problems.