Microbiota and Protein-energy Wasting (MIDIWA)
Summary
Oral supplementation with branched chain amino acids (BCAA) increases the levels of circulating BCAA, stimulates BCAA uptake in muscles, and decreases amino acid release from muscle, eventually promoting muscle anabolism. However, uptake of oral BCAA by muscle is not complete, pointing out that non-muscular tissues, as the splanchnic bed and gut microbiota, may play a role in BCAA metabolism.
This protocol aims at studying the impact of protein-energy wasting (PEW) and of refeeding with branched chain amino acids (BCAA), on gut barrier including gut microbiota, in chronic hemodialysis (HD) patients. The investigators speculate that:
1. HD patients with PEW have altered composition and function of gut microbiota, increased permeability of epithelial gut barrier, increased systemic inflammation but decreased fecal immunoglobulin A (IgA), and a dysbalance of plasma appetite mediators in favor of anorexigenic mediators, compared to HD patients without PEW, non dialyzed patients with chronic kidney disease and well-nourished non obese subjects,
2. BCAA supplementation of HD patients with PEW reverses these changes, thereby improving nutritional state, physical function, quality of life and resistance to infections.
Description
General description :
This protocol is multicenter (University Hospitals of Geneva (HUG) and Lausanne (CHUV) and Sion (HVS)) and encompasses two parts, a cross-sectional and a longitudinal study:
1. Cross-sectional study: It is performed to differentiate the respective impact of uremia and protein-energy wasting (PEW) on gut barrier and gut microbiota. It will compare gut barrier of hemodialysis (HD) patients with PEW, with gut barrier of age-matched HD well-nourished patients, non dialyzed patients with chronic kidney disease (CKD), and healthy non obese volunteers (10 in each group). This study part is essential for interpretation of the changes occurring in the longitudinal study.
2. Longitudinal double blind randomized crossover study: HD patients with PEW (36 patients), receive, in a randomized double-blind order, either BCAA or an isocaloric isonitrogenous placebo for 4 months each, with a wash-out period of 1 month.
Randomization :
1. Cross-sectional study: No randomization will be performed. HD patients without PEW, non dialyzed patients with CKD and healthy non obese volunteers will be included if matched for gender and age with the included HD patients with PEW.
2. Longitudinal study: Sequence assignment will be randomized separately in each center to ensure an equal percentage of each sequence in both centers. For this purpose, the investigators will generate 2 lists of randomization with the method of randomly permuted blocks with random block sizes of 2 and 4.
Recruitment :
Patients will be recruited among the outpatients of the Nephrology Divisions or Services of the HUG, CHUV and HVS. Healthy volunteers will be recruited among hospital staff or their relatives.
Inclusion Criteria :
1. HD patients with PEW
- Age ≥ 18 years.
- Maintenance HD for at least 3 months.
- Fasting predialysis plasma albumin < 38 g/l in the absence of plasma C-reactive protein > 50 mg/l in the last 2 weeks or known acute infection.
- Dietary intakes (24h dietary recall) between 20-30 kcal/kg/d and < 1 g protein/kg/d on one occasion, during screening. These intakes will not include the intake of oral nutritional supplements, as intakes below 20 kcal/kg/d request artificial nutrition.
2. HD patients without PEW
- Patients matched for age and gender to HD patients with PEW.
- Maintenance HD for at least 3 months.
- Fasting predialysis plasma albumin ≥ 40 g/l, in the absence of plasma C-reactive protein > 50 mg/l in the last 2 weeks or known acute infection.
- Dietary intakes (24h dietary recall) > 30 kcal/kg/d and > 1.2 g protein/kg/d, once during screening.
3. Non dialyzed patients with chronic kidney disease stage 4
- Patients matched for age and gender to HD patients with PEW.
- Chronic kidney disease, stage 4, not requiring HD.
- Fasting predialysis plasma albumin ≥ 40 g/l, in the absence of plasma C-reactive protein > 50 mg/l in the last 2 weeks or known acute infection.
- Dietary intakes (24h dietary recall) > 30 kcal/kg/d and > 1.2 g protein/kg/d, once during screening.
4. Healthy non obese volunteers
- Subjects matched for age and gender to HD patients with PEW.
- Body mass index < 30 kg/m2
- Absence of chronic disease potentially leading to wasting or cachexia.
- Absence of plasma C-reactive protein > 50 mg/l in the last 2 weeks or known acute infection.
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care
Conditions
Undernutrition
Intervention
Branched chain amino acids (BCAA), Placebo
Location
Hôpital du Valais
Sion
Valais
Switzerland
1951
Status
Recruiting
Source
University Hospital, Geneva
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT02962089
- ClinicalTrials.gov processed this data on November 14, 2016
Published on BioPortfolio: 2016-11-15T11:38:21-0500
Clinical Trials
Plasma Free Amino Acids in Patients With Hepatic Encephalopathy
This is study to investigate the plasma free amino acids profile in patients with decompensated liver cirrhosis and hepatic encephalopathy and its relation to the nutritional state of thes...
The aims of this study are (1) to study the benefit of branched-chain amino acids enriched nutrient-mixture by analyzing a variety of clinical parameter, including laboratory data, the dur...
The purpose of this study is to determine whether Branched chain Amino Acids enhances the uptake of ammonia in muscle tissue.
Effects of Chronic Dietary Exposure to Branched Chain Amino Acids
Branched-chain amino acids (BCAA) belong among nutrients strongly linked with insulin sensitivity (IS) measures. Their exact effect on IS appears to be dependent on various conditions that...
Effect of Branched Chain Amino Acids on Muscle
With aging, there is a decrease in muscle mass and function especially in the energy storehouses of cells called mitochondria. Amino acids, the building blocks of protein, and insulin hav...
PubMed Articles
Diabetes and branched chain amino acids: What is the link?
The branched chain amino acids (BCAA) have increasingly been studied as playing a role in diabetes, with the PubMed search string "diabetes AND "branched chain amino acids" showing particular growth i...
Branched-chain amino acid metabolism in cancer.
The current review aims to provide an update on the recent biomedical interest in oncogenic branched-chain amino acid (BCAA) metabolism, and discusses the advantages of using BCAAs and expression of B...
The purpose of this investigation was to examine the individual and combined effects of ingesting carbohydrates (CHO) and branched chain amino acids (BCAA) during high volume upper-body resistance exe...
Branched chain amino acids (BCAA) are catabolized into various acyl-CoA compounds, which are key precursors used in polyketide productions. Because of that, BCAA catabolism needs fine tuning of flux b...
High-fat high-sucrose diet (HFHS) overfeeding is one of the main factors responsible for the increased prevalence of metabolic disorders. Elevated levels of branched-chain amino acids (BCAAs) have bee...
Medical and Biotech [MESH] Definitions
Amino Acids, Branched-chain
Amino acids which have a branched carbon chain.
Multiple Acyl Coenzyme A Dehydrogenase Deficiency
An autosomal recessive disorder of fatty acid oxidation, and branched chain amino acids (AMINO ACIDS, BRANCHED-CHAIN); LYSINE; and CHOLINE catabolism, that is due to defects in either subunit of ELECTRON TRANSFER FLAVOPROTEIN or its dehydrogenase, electron transfer flavoprotein-ubiquinone oxidoreductase (EC 1.5.5.1).
Maple Syrup Urine Disease
An autosomal recessive inherited disorder with multiple forms of phenotypic expression, caused by a defect in the oxidative decarboxylation of branched-chain amino acids (AMINO ACIDS, BRANCHED-CHAIN). These metabolites accumulate in body fluids and render a "maple syrup" odor. The disease is divided into classic, intermediate, intermittent, and thiamine responsive subtypes. The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. (From Adams et al., Principles of Neurology, 6th ed, p936)
Leucine Transaminase
A PYRIDOXAL PHOSPHATE containing enzyme that catalyzes the reversible transamination of branched-chain AMINO ACIDS to 2-oxoglutarate.
Peptides
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
