Effects of Short-chain Fatty Acids on Inflammatory and Metabolic Parameters in Maintenance Hemodialysis

NCT02976688 | Unknown Phase 2

• 1 other identifier: ASL AVELLINO
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

End-stage renal disease (ESRD) is associated with multiple comorbidities such as cardiovascular disease, anemia, mineral and bone disorders, malnutrition, body wasting, muscle loss (sarcopenia), neurological problems and infections resulting in a poor survival. In the pathogenesis of the uremic syndrome the altered intestinal function seems to be an important contributor. While the normal gut microbiota plays a prominent role in the maintenance of health and disease prevention, changes of its composition is associated with numerous diseases such as obesity, type 2 diabetes, cardiovascular disturbances and auto-immune diseases.In ESRD metabolic alterations of uremia results in quantitative and qualitative changes of its bacterial flora with an overgrowth of pathobionts (1). Due to concomitant disruption of the intestinal barrier function, noxious luminal products are translocated in the body's internal milieu (2).The accumulation of these compounds correlates with systemic inflammation, protein wasting and accelerated cardiovascular complications in hemodialysis patients (3). Short-chain fatty acids (SCFA) are produced in the colon and distal small intestine by anaerobic bacteria following fermentation of complex carbohydrates.They have been shown to exert anti-inflammatory, anti-cancer, antibacterial and antidiabetic effects (4). Supplementation of SCFA exerts anti-inflammatory actions both in intestinal epithelial cells (5) and in the cardiovascular system (6). They also positively influence auto- immune reactions /diseases (7,8). In this study we want to investigate in MHD patients whether a treatment with SCFA in form of sodium propionate (SP) modulates the systemic inflammation, insulin resistance and accumulation of intestinal uremic toxins.

Conditions

Endstage Renal Disease

Keywords

Endstage renal Disease; Hemodialysis

Outcome Measures

Primary Outcomes (8)

• Variation from the beginning to the study end of serum inflammatory biomarkers

  endotoxin /lipopolysaccharide levels, high sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-10, IL-2, INFγ, TGFβ, IL-4, IL-1β, IL-17a and white blood cell count.

  16 weeks

• Variation from the beginning to the study end of serum oxidative stress biomarkers

  glutathione peroxidase, malone dialdehyde

  16 weeks

• Variation from the beginning to the study end of insulin resistance

  Determination of Homa Index (Homeostasis Model Assessment) by measurement fasting blood sugar and insulin level as well as hemoglobin HbA1c. IR appears to be as associated of metabolic disorders including lipid abnormalities, atherosclerotic cardiovascular disease and accelerated muscle protein degradation (Wang et al. 2006). IL is induced in particular by systemic inflammation.

  16 weeks

• Variation from the beginning to the study end of serum lipid levels

  Triglycerides, total cholesterol, high and low density cholesterol

  16 weeks

• Variation from the beginning to the study end of hormonal parameter

  Leptin, resistin, adiponectin and glucagon-like peptide -1.

  16 weeks

• Variation from the beginning to the study end of uremic toxins produced in the intestinal tract

  p-cresyl sulfate, indoxyl sulfate and trimethylamine -N-oxide

  16 weeks

• Variation from the beginning to the study end of nutritional status

  Serum albumin

  16 weeks

• Variation from the beginning to the study end of parameters of well-being

  patient reported health (SF-36).

  16 weeks

Study Arms (1)

Sodium propionate

EXPERIMENTAL

Sodium propionate will be administered with a daily intake of 2 x 500 mg in form of capsules for 12 weeks.

Other: Sodium Propionate

Interventions

Sodium Propionate OTHER

Sodium propionate is a non-toxic food additive, confirmed and licensed by the European Food Safety Authority (EFSA) sodium propionate E281. We are planning the oral application of 500 mg SP 2x per day. This dose is about 0.014 mg/kg of the body weight. Therefore, no risk of toxicity is expected in the patients.

Also known as: Sodium propionate E281

Sodium propionate

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stable hemodialysis patients treated by renal replacement therapy for at least 6 months
• Written informed consent written

You may not qualify if:

• Patients with malnutrition, infections, carcinoma, previous renal transplant, intestinal diseases (medically diagnosed irritable bowel syndrome, Crohn's disease, ulcerative colitis and diarrhea) and antibiotic treatment within one month of study will be excluded.

Sponsors & Collaborators

• Azienda Sanitaria ASL Avellino 2: lead

Related Publications (33)

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MeSH Terms

Interventions

sodium propionate

Study Officials

• Biagio Di Iorio, Chief, PhD

  ASL AVELLINO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Biagio Di Iorio, Chief, PhD

CONTACT

00390825530366; br.diiorio@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr, Chief Nephrology Division

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 29, 2016
• Study Start: January 1, 2017
• Primary Completion: July 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 29, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share