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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02976688
Recruitment Status : Unknown
Verified November 2016 by Dr Biagio Di Iorio, Azienda Sanitaria ASL Avellino 2.
Recruitment status was:  Not yet recruiting
First Posted : November 29, 2016
Last Update Posted : November 29, 2016
Information provided by (Responsible Party):
Dr Biagio Di Iorio, Azienda Sanitaria ASL Avellino 2

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.

Condition or disease Intervention/treatment Phase
Endstage Renal Disease Other: Sodium Propionate Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Short-chain Fatty Acids, Here Sodium Propionate, a Metabolism Product of the Human Gut-microbiome, on Inflammatory and Metabolic Parameters in Patients on Maintenance Hemodialysis - a Pilot Study
Study Start Date : January 2017
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : December 2017

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Arm Intervention/treatment
Experimental: Sodium propionate
Sodium propionate will be administered with a daily intake of 2 x 500 mg in form of capsules for 12 weeks.
Other: Sodium Propionate
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.
Other Name: Sodium propionate E281

Primary Outcome Measures :
  1. Variation from the beginning to the study end of serum inflammatory biomarkers [ Time Frame: 16 weeks ]
    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.

  2. Variation from the beginning to the study end of serum oxidative stress biomarkers [ Time Frame: 16 weeks ]
    glutathione peroxidase, malone dialdehyde

  3. Variation from the beginning to the study end of insulin resistance [ Time Frame: 16 weeks ]
    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.

  4. Variation from the beginning to the study end of serum lipid levels [ Time Frame: 16 weeks ]
    Triglycerides, total cholesterol, high and low density cholesterol

  5. Variation from the beginning to the study end of hormonal parameter [ Time Frame: 16 weeks ]
    Leptin, resistin, adiponectin and glucagon-like peptide -1.

  6. Variation from the beginning to the study end of uremic toxins produced in the intestinal tract [ Time Frame: 16 weeks ]
    p-cresyl sulfate, indoxyl sulfate and trimethylamine -N-oxide

  7. Variation from the beginning to the study end of nutritional status [ Time Frame: 16 weeks ]
    Serum albumin

  8. Variation from the beginning to the study end of parameters of well-being [ Time Frame: 16 weeks ]
    patient reported health (SF-36).

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

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 identifier (NCT number): NCT02976688

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Contact: Biagio Di Iorio, Chief, PhD 00390825530366

Sponsors and Collaborators
Azienda Sanitaria ASL Avellino 2
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Principal Investigator: Biagio Di Iorio, Chief, PhD ASL AVELLINO

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Responsible Party: Dr Biagio Di Iorio, Dr, Chief Nephrology Division, Azienda Sanitaria ASL Avellino 2 Identifier: NCT02976688    
Other Study ID Numbers: ASL AVELLINO
First Posted: November 29, 2016    Key Record Dates
Last Update Posted: November 29, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Dr Biagio Di Iorio, Azienda Sanitaria ASL Avellino 2:
Endstage renal Disease
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency