Microbiota and Protein-energy Wasting (MIDIWA)

NCT02962089 | Completed DMC

• 1 other identifier: CER 13-239
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 5

Brief 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. 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. 2.BCAA supplementation of HD patients with PEW reverses these changes, thereby improving nutritional state, physical function, quality of life and resistance to infections.

Conditions

Undernutrition

Keywords

Protein-energy wasting; Hemodialysis patients; Microbiota; Branched chain amino acids; Undernutrition; Malnutrition; Renal failure; Dialysis; Protein; Appetite; Body composition; Energy expenditure

Outcome Measures

Primary Outcomes (2)

• Gut microbiota composition by 16-S high throughput sequencing

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

• Gut microbiota function by 16-S high throughput sequencing

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

Secondary Outcomes (20)

• Epithelial gut barrier function by fasting level of plasma glucagon-like peptide-2

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

• Epithelial gut barrier function by fasting level of plasma lipopolysaccharide

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

• Intestinal immunity by level of fecal IgA

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

• Systemic inflammation by fasting level of plasma interleukin 10

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

• Systemic inflammation by fasting level of plama interleukin 6

  Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Isocaloric isonitrogenous placebo for 4 months (7g, twice daily)

Dietary Supplement: Placebo

Branched chain amino acids (BCAA)

ACTIVE COMPARATOR

BCAA mixture for 4 months (7g, twice daily)

Dietary Supplement: Branched chain amino acids (BCAA)

Interventions

Branched chain amino acids (BCAA) DIETARY_SUPPLEMENT

Branched chain amino acids (BCAA)

Placebo DIETARY_SUPPLEMENT

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Maintenance hemodialysis for at least 3 months.
• Fasting predialysis plasma albumin \< 38 g/l in the absence of any known acute infection during the last 2 weeks or body weight loss \> 5% of estimated dry body weight over 3 months
• 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

You may not qualify if:

• Known psychiatric or cognitive disorder, precluding protocol compliance.
• Life expectancy below 1 year.
• Inadequate dialysis (Kt/V\<1.2 on 3 consecutive occasions, for HD patients only), if applicable.
• Enteral or parenteral nutrition.
• Drugs or oral nutritional supplements containing fibers since ≤ 1 month.
• Known reasons for decreased plasma albumin levels as liver failure or exudative enteropathy.
• Drugs influencing body composition, ≤ 1 month : systemic corticosteroids, anabolic drugs as insulin or testosterone, post-menopausal hormone therapy, injectable contraceptives.
• Known endocrinological disorders potentially leading to hypo- or hypermetabolism, untreated or treated since ≤ 1 month : disorders of thyroid gland, adrenal glands...
• Pregnancy and breast-feeding.

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (5)

Cécil clinic

Lausanne, Canton of Vaud, 1003, Switzerland

Location

Lausanne University Hospital

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Hospital of Sion

Sion, Valais, 1951, Switzerland

Location

Geneva University Hospital

Geneva, 1205, Switzerland

Location

Champel clinic

Geneva, 1206, Switzerland

Location

Related Publications (2)

• Genton L, Pruijm M, Teta D, Bassi I, Cani PD, Gaia N, Herrmann FR, Marangon N, Mareschal J, Muccioli GG, Stoermann C, Suriano F, Wurzner-Ghajarzadeh A, Lazarevic V, Schrenzel J. Gut barrier and microbiota changes with glycine and branched-chain amino acid supplementation in chronic haemodialysis patients. J Cachexia Sarcopenia Muscle. 2021 Dec;12(6):1527-1539. doi: 10.1002/jcsm.12781. Epub 2021 Sep 18.

  PMID: 34535959 DERIVED

• Genton L, Teta D, Pruijm M, Stoermann C, Marangon N, Mareschal J, Bassi I, Wurzner-Ghajarzadeh A, Lazarevic V, Cynober L, Cani PD, Herrmann FR, Schrenzel J. Glycine increases fat-free mass in malnourished haemodialysis patients: a randomized double-blind crossover trial. J Cachexia Sarcopenia Muscle. 2021 Dec;12(6):1540-1552. doi: 10.1002/jcsm.12780. Epub 2021 Sep 14.

  PMID: 34519439 DERIVED

MeSH Terms

Conditions

Malnutrition; Renal Insufficiency

Interventions

Amino Acids

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Officials

• Laurence Genton, MD

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician at Clinical Nutrition Unit

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: November 11, 2016
• Study Start: August 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (5)