Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease

NCT04067752 | Completed DMC

• 1 other identifier: NEPH-010-18F
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

By 2030 an estimated 2 million people in the US will need dialysis or transplantation. Insulin resistance and chronic inflammation are common in dialysis patients and have been linked to protein-energy wasting, the most important determinant of clinical outcome in this patient population. The investigators hypothesize that the skin and muscle tissue sodium accumulation is a critical mechanism by which chronic inflammatory response and insulin resistance, alone or in combination lead to protein energy wasting in hemodialysis patients. The investigators will test this hypothesis by studying dialysis patients and matched controls without kidney disease by examining tissue Na content, markers of inflammation and protein metabolism.

Conditions

End-stage Renal Disease

Keywords

dialysis; ESRD; hemodialysis; MRI

Outcome Measures

Primary Outcomes (4)

• Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min

  Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min. This reflects the balance between endogenous leucine appearance rate (protein synthesis), the leucine oxidation rate, and the non-oxidative leucine disappearance rate (protein breakdown).

  4 weeks

• Net skeletal muscle protein balance measured by stable isotope technique reported as g/100 ml/min

  Net skeletal muscle protein balance measured by stable isotope technique reported as g/100 ml/min. This reflects the dilution and enrichment of phenylalanine across the forearm. Because phenylalanine is neither synthesized nor metabolized by skeletal muscle, rate of appearance (Ra) of unlabeled phenylalanine reflects muscle protein breakdown, whereas the rate of disappearance (Rd) of labeled phenylalanine estimates muscle protein synthesis. the difference between synthesis and breakdown provides net skeletal muscle protein balance at a given rate of blood flow.

  4 weeks

• Muscle sodium content

  Muscle sodoium content measured by NAMRI before and after intervention

  4 weeks

• Skin sodium content

  Skin sodium content measured by NAMRI before and after intervention

  4 weeks

Secondary Outcomes (9)

• Handgrip strength measured by dynamometer

  4 weeks

• Recovery time

  4 weeks

• Pulse Wave Velocity

  4 weeks

• Interleukin 6

  4 weeks

• Sit to stand test

  4 weeks

Study Arms (2)

High Dialysate Na

EXPERIMENTAL

high dialysate sodium concentration (138 mEq/L)

Other: high dialysate sodium concentration (138 mEq/L)

Low Dialysate Na

ACTIVE COMPARATOR

Low dialysate sodium concentration (132 mEq/L)

Other: Low dialysate sodium concentration

Interventions

high dialysate sodium concentration (138 mEq/L) OTHER

high dialysate sodium concentration (138 mEq/L)

High Dialysate Na

Low dialysate sodium concentration OTHER

low dialysate sodium concentration (132 mEq/L)

Low Dialysate Na

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• On MHD for more than 6 months
• Have acceptable dialysis adequacy (eKt/V \> 1.2) for a minimum of 3 months and a patent, well-functioning, hemodialysis AV access
• Ability to give informed consent

You may not qualify if:

• Pregnancy
• Intolerance to the medication in metabolic studies)
• Presence of a metal object in the body that might interfere with MRI
• Severe, unstable, active, or chronic inflammatory disease (active infection, active connective tissue disorder, active cancer or cancer history in the prior 5 years, HIV, liver disease, active chronic hepatitis B or C)
• Type 1 Diabetes on insulin therapy; Hospitalization within 1 month prior to the study
• Receiving steroids (including inhaled steroid and high potency topical, with the exception of over the counter hydrocortisone cream
• Prednisone \> 5 mg/day) and/or other immunosuppressive agents
• Residual renal function \> 5ml/min or urine output \> 400 ml/day

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

Location

Vanderbilt University Medical center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Ertuglu LA, Sahinoz M, Alsouqi A, Deger SM, Guide A, Pike M, Robinson-Cohen C, Akwo E, Pridmore M, Crescenzi R, Madhur MS, Kirabo A, Harrison DG, Luft FC, Titze J, Ikizler TA, Gamboa JL. Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals. Physiol Rep. 2024 Jul;12(13):e16127. doi: 10.14814/phy2.16127.

  PMID: 38960895 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Talat A Ikizler, MD

  Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The patients will be randomized by computer generated sequence and study coordinators and co-investigators other than the primary investigator will be unblended to the treatment arms. The data will be sent to biostatistician with no identifiable information regarding randomization arms.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: The design is randomized, cross-over, double-blind, placebo-controlled. Once the subject is determined to be eligible for the study, we will randomly assign him/her to one of the study arms (Dialysate Na concentration 138 mEq/L versus 132 mEq/L)

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 26, 2019
• Study Start: March 1, 2022
• Primary Completion: May 15, 2024
• Study Completion: May 20, 2024
• Last Updated: November 8, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)