A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis

J Cachexia Sarcopenia Muscle. 2024 Feb;15(1):401-411. doi: 10.1002/jcsm.13395. Epub 2024 Jan 4.

Abstract

Background: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD.

Methods: Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks. Changes in serum inflammatory markers and insulin-mediated protein synthesis, breakdown and net balance in the whole-body and skeletal muscle compartments were assessed using hyperinsulinaemic-hyperaminoacidemic clamp technique at baseline and Week 12.

Results: Among 24 patients, median (interquartile range) age was 51 (40, 61), 79% were African American and 21% had diabetes mellitus. All patients initiated on intervention completed the study, and no serious adverse events were observed. There was a statistically significant decrease in serum high-sensitivity C-reactive protein in the pioglitazone group compared with placebo, but not in the IL-1ra group. No significant differences in the changes of whole-body or skeletal muscle protein synthesis, breakdown and net balance were found between the groups.

Conclusions: In this pilot study, there were no statistically significant effects of 12 weeks of IL-1ra or pioglitazone on protein metabolism in patients on MHD.

Clinicaltrials: gov registration: NCT02278562.

Keywords: inflammation; insulin resistance; maintenance haemodialysis; protein metabolism.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Biomarkers
  • Humans
  • Insulin
  • Interleukin 1 Receptor Antagonist Protein* / therapeutic use
  • Pilot Projects
  • Pioglitazone / therapeutic use
  • Renal Dialysis*

Substances

  • Pioglitazone
  • Interleukin 1 Receptor Antagonist Protein
  • Insulin
  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT02278562