Muscle Protein Synthesis in Dialysis Patients

NCT03478722 | Completed

• 1 other identifier: 16203
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The most severe form of chronic renal failure is end-stage-renal-disease with maintenance hemodialysis (MHD) as the most common treatment strategy. MHD patients experience a number of metabolic and phenotypic derangements including skeletal muscle wasting. Previously, it has been demonstrated that dialysis treatment leads to increased rates of forearm phenylalanine uptake (proxy for 'muscle' protein synthesis) with an even greater rates of phenylalanine release (proxy for 'muscle' protein breakdown). Hence, the dialysis procedure itself is catabolic and induces a catabolic carryover for several hours after dialysis. This suggests prolonged post-dialysis disturbances in whole body- and skeletal muscle protein metabolism in MHD patients. Moreover, dialysis treatment in itself results in \~20 % losses of circulating amino acids in the dialysate. Collectively, this creates the need for replacement of amino acids by protein supplementation during and/or after dialysis. The ingestion of protein-dense meals in between dialysis treatments likely represents an important dietary strategy to counterbalance dialysis-induced catabolism and to achieve the current recommended protein intakes (set at 1.2 g/kg bodyweight/d) to limit muscle protein loss in MHD patients. However, the effectiveness of protein-rich meal ingestion to augment postprandial whole body and muscle protein metabolic responses in MHD patients outside of the dialysis period remain largely undefined. The purpose of this study is to compare basal and postprandial whole body leucine body kinetics, muscle anabolic sensing mechanisms, markers of muscle proteolysis, and myofibillar protein synthesis rates to mixed meal ingestion on a non-dialysis day in eight MHD patients, between 20-80 and to compare these outcomes to age- and BMI-matched controls. The investigators will use specifically produced intrinsically L-\[5,5,5-2H3\]leucine labeled eggs combined with primed constant amino acid tracer infusion methods and concomitant blood and muscle direct sampling to make direct assessments of in vivo protein digestion and absorption kinetics and subsequent postprandial muscle protein synthetic responses in MHD patents and controls. On the test day, subjects will remain sedentary for the determination of muscle protein synthesis in both the fasted state and after consumption of the meal.

Conditions

Muscle Loss

Outcome Measures

Primary Outcomes (1)

• Fractional synthetic rate of myofibrillar proteins

  Measurement of muscle protein synthesis

  8 hours

Study Arms (2)

Maintenance Hemodialysis Patients

Protein meal, stable isotope amino acid infusion

Other: Protein Meal; Other: Stable Isotope Amino Acid Infusion

Control Subjects

Protein meal, stable isotope amino acid infusion

Other: Protein Meal; Other: Stable Isotope Amino Acid Infusion

Interventions

Protein Meal OTHER

Ingestion of mixed meal containing 20 g of dietary protein

Control Subjects; Maintenance Hemodialysis Patients

Stable Isotope Amino Acid Infusion OTHER

Continuous infusion of L-\[1-13C\]leucine (0.13 μmol⋅kg⋅min) and L-\[ring- 2H5\]phenylalanine (0.05 μmol⋅kg⋅min)

Control Subjects; Maintenance Hemodialysis Patients

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In total, the investigators would like to recruit 8 maintenance hemodialysis patients (both male and female) and 8 healthy controls matched for gender, age and BMI.

You may qualify if:

• Aged 20-80 years (both healthy controls and MHD patients)
• Medical clearance from a Nephrologist at their respective dialysis clinic to participate (MHD patients)

You may not qualify if:

• Known allergies to egg consumption (both healthy controls and MHD patients)
• Phenylketonuria (both healthy controls and MHD patients)
• Vegans (both healthy controls and MHD patients)
• Diagnosed GI tract diseases (healthy controls)
• Recent (1 year) participation in amino acid tracer studies (both healthy controls and MHD patients)
• Predisposition to hypertrophic scarring or keloid formation (both healthy controls and MHD patients)
• Diabetes (healthy controls)
• Pregnancy (both healthy controls and MHD patients)

Sponsors & Collaborators

• University of Illinois at Urbana-Champaign: lead

Study Sites (1)

Freer Hall

Urbana, Illinois, 61801, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples and skeletal muscle tissue biopsies

MeSH Terms

Conditions

Muscular Atrophy

Interventions

guar meal protein, Cyamopsis tetragonoloba

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Nicholas A Burd, PhD

  University of Illinois, Urbana-Champaign

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: March 27, 2018
• Study Start: January 18, 2017
• Primary Completion: December 15, 2017
• Study Completion: April 1, 2018
• Last Updated: May 1, 2018

Record last verified: 2018-03

Locations

US (1)