Effects of Short-chain Fatty Acids on Inflammatory and Metabolic Parameters in Maintenance Hemodialysis (PLAN)
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|ClinicalTrials.gov 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
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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.
- Variation from the beginning to the study end of serum oxidative stress biomarkers [ Time Frame: 16 weeks ]glutathione peroxidase, malone dialdehyde
- 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.
- Variation from the beginning to the study end of serum lipid levels [ Time Frame: 16 weeks ]Triglycerides, total cholesterol, high and low density cholesterol
- Variation from the beginning to the study end of hormonal parameter [ Time Frame: 16 weeks ]Leptin, resistin, adiponectin and glucagon-like peptide -1.
- 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
- Variation from the beginning to the study end of nutritional status [ Time Frame: 16 weeks ]Serum albumin
- Variation from the beginning to the study end of parameters of well-being [ Time Frame: 16 weeks ]patient reported health (SF-36).
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 ClinicalTrials.gov identifier (NCT number): NCT02976688
|Contact: Biagio Di Iorio, Chief, PhDfirstname.lastname@example.org|
|Principal Investigator:||Biagio Di Iorio, Chief, PhD||ASL AVELLINO|