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Microbiota and Protein-energy Wasting (MIDIWA) (MIDIWA)

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ClinicalTrials.gov Identifier: NCT02962089
Recruitment Status : Recruiting
First Posted : November 11, 2016
Last Update Posted : May 3, 2018
Sponsor:
Information provided by (Responsible Party):
Genton Graf Laurence, University Hospital, Geneva

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. 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.

Condition or disease Intervention/treatment Phase
Undernutrition Dietary Supplement: Branched chain amino acids (BCAA) Dietary Supplement: Placebo Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Do Branched Chain Amino Acids Counteract Protein Energy Wasting Through Gut Microbiota Changes in Hemodialysis Patients ?
Study Start Date : August 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Isocaloric isonitrogenous placebo for 4 months (7g, twice daily)
Dietary Supplement: Placebo
Active Comparator: Branched chain amino acids (BCAA)
BCAA mixture for 4 months (7g, twice daily)
Dietary Supplement: Branched chain amino acids (BCAA)



Primary Outcome Measures :
  1. Gut microbiota composition by 16-S high throughput sequencing [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  2. Gut microbiota function by 16-S high throughput sequencing [ Time Frame: 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 Outcome Measures :
  1. Epithelial gut barrier function by fasting level of plasma glucagon-like peptide-2 [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  2. Epithelial gut barrier function by fasting level of plasma lipopolysaccharide [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  3. Intestinal immunity by level of fecal IgA [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  4. Systemic inflammation by fasting level of plasma interleukin 10 [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  5. Systemic inflammation by fasting level of plama interleukin 6 [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  6. Systemic inflammation by fasting level of plama tumor necrosis factor alpha [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  7. Appetite by fasting level of plasma cholecystokinin [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  8. Appetite by fasting level of plasma leptin [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  9. Appetite by fasting level of plasma peptide YY [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  10. Appetite by fasting level of plasma glucagon-like peptide-1 [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  11. Appetite by fasting level of plasma neuropeptide Y [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  12. Appetite by fasting level of plasma ghrelin [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  13. Appetite by fasting level of plasma endocannabinoids [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  14. Calorie and protein intakes by 3-day food diary [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  15. Body composition by dual-energy x-rax absorptiometry (DEXA) [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  16. Resting energy expenditure (REE) by indirect calorimetry [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  17. Physical activity level by 7-day pedometry [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  18. Handgrip strength by dynamometer [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]
  19. Quality of life score by Short Form Health Survey (SF-36) [ Time Frame: Changes between baseline and end of each treatment (i.e.changes between Month 0 and Month 4 and between Month 5 and Month 9) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Absence of any systematic antibiotic treatment for an acute infection in the month preceding the inclusion

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02962089


Contacts
Contact: Julie Mareschal, BSc 0041 79 553 33 86 julie.mareschal@hcuge.ch

Locations
Switzerland
Hôpital du Valais Recruiting
Sion, Valais, Switzerland, 1951
Contact: Daniel Teta, MD, PhD    0041 27 603 42 40    daniel.teta@hopitalvs.ch   
Lausanne University Hospital Recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Menno Pruijm, PD, MER1    0041 21 314 13 58    menno.pruijm@chuv.ch   
Geneva University Hospital Recruiting
Geneva, Switzerland, 1205
Contact: Laurence Genton, MD    0041 22 37 29 344    laurence.genton@hcuge.ch   
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Laurence Genton, MD University Hospital, Geneva

Responsible Party: Genton Graf Laurence, Associate Physician at Clinical Nutrition Unit, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT02962089     History of Changes
Other Study ID Numbers: CER 13-239
First Posted: November 11, 2016    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Genton Graf Laurence, University Hospital, Geneva:
Protein-energy wasting
Hemodialysis patients
Microbiota
Branched chain amino acids
Undernutrition
Malnutrition
Renal failure
Dialysis
Protein
Appetite
Body composition
Energy expenditure

Additional relevant MeSH terms:
Cachexia
Wasting Syndrome
Malnutrition
Emaciation
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Metabolic Diseases
Nutrition Disorders