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
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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.
