<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02976688</url>
  </required_header>
  <id_info>
    <org_study_id>ASL AVELLINO</org_study_id>
    <nct_id>NCT02976688</nct_id>
  </id_info>
  <brief_title>Effects of Short-chain Fatty Acids on Inflammatory and Metabolic Parameters in Maintenance Hemodialysis</brief_title>
  <acronym>PLAN</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Sanitaria ASL Avellino 2</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Sanitaria ASL Avellino 2</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      End-stage renal disease (ESRD) is associated with multiple comorbidities such as&#xD;
      cardiovascular disease, anemia, mineral and bone disorders, malnutrition, body wasting,&#xD;
      muscle loss (sarcopenia), neurological problems and infections resulting in a poor survival.&#xD;
&#xD;
      In the pathogenesis of the uremic syndrome the altered intestinal function seems to be an&#xD;
      important contributor. While the normal gut microbiota plays a prominent role in the&#xD;
      maintenance of health and disease prevention, changes of its composition is associated with&#xD;
      numerous diseases such as obesity, type 2 diabetes, cardiovascular disturbances and&#xD;
      auto-immune diseases.In ESRD metabolic alterations of uremia results in quantitative and&#xD;
      qualitative changes of its bacterial flora with an overgrowth of pathobionts (1). Due to&#xD;
      concomitant disruption of the intestinal barrier function, noxious luminal products are&#xD;
      translocated in the body's internal milieu (2).The accumulation of these compounds correlates&#xD;
      with systemic inflammation, protein wasting and accelerated cardiovascular complications in&#xD;
      hemodialysis patients (3).&#xD;
&#xD;
      Short-chain fatty acids (SCFA) are produced in the colon and distal small intestine by&#xD;
      anaerobic bacteria following fermentation of complex carbohydrates.They have been shown to&#xD;
      exert anti-inflammatory, anti-cancer, antibacterial and antidiabetic effects (4).&#xD;
      Supplementation of SCFA exerts anti-inflammatory actions both in intestinal epithelial cells&#xD;
      (5) and in the cardiovascular system (6). They also positively influence auto- immune&#xD;
      reactions /diseases (7,8).&#xD;
&#xD;
      In this study we want to investigate in MHD patients whether a treatment with SCFA in form of&#xD;
      sodium propionate (SP) modulates the systemic inflammation, insulin resistance and&#xD;
      accumulation of intestinal uremic toxins.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      End-stage renal disease (ESRD) is associated with multiple comorbidities such as&#xD;
      cardiovascular disease, anemia, mineral and bone disorders, malnutrition, body wasting,&#xD;
      muscle loss (sarcopenia), neurological problems and infections resulting in a poor survival.&#xD;
      Important promoters of these obstacles are enhanced generation of reactive oxygen species&#xD;
      (ROS), systemic inflammation, acquired immunodeficiency (9, 10) and an impaired glucose and&#xD;
      insulin homeostasis (11).&#xD;
&#xD;
      Systemic inflammation and oxidative stress in ESRD are induced by activation of the innate&#xD;
      immune system involving monocytes, macrophages, granulocytes and cellular constituents&#xD;
      (endothelial cell activation) as well as depletion of natural regulatory T cells that impairs&#xD;
      their ability to suppress inflammation .The concomitant reduced humoral immunity is favored&#xD;
      by depletion of antigen presenting dendritic cells, a lowered CD44/CD8 T cell ratio,&#xD;
      depletion of naïve and central memory T cells, diffuse B cell lymphopenia and an impaired&#xD;
      phagocytic ability of monocytes and PMNs (12).&#xD;
&#xD;
      Insulin resistance (IR) participates in the pathogenesis of multiple metabolic and&#xD;
      cardiovascular disturbances (13) and is an important factor of the accelerated muscle protein&#xD;
      degradation in ESRD (14). Underlying mechanisms of IR are the metabolic inflammation, in&#xD;
      particular elevated LPS levels.&#xD;
&#xD;
      In the pathogenesis of the uremic syndrome the altered intestinal function seems to be an&#xD;
      important contributor. While the normal gut microbiota plays a prominent role in the&#xD;
      maintenance of health and disease prevention, changes of its composition is associated with&#xD;
      numerous diseases such as obesity, type 2 diabetes, cardiovascular disturbances and&#xD;
      auto-immune diseases. In ESRD metabolic alterations of uremia results in quantitative and&#xD;
      qualitative changes of its bacterial flora with an overgrowth of pathobionts (1). Due to&#xD;
      concomitant disruption of the intestinal barrier function, noxious luminal products are&#xD;
      translocated in the body's internal milieu (Fig.2). The passage includes whole bacteria&#xD;
      (going into mesenteric lymph nodes), endotoxins/ lipoproteinlipase (LPS) (cell wall&#xD;
      components of the bacteria) and other noxious luminal products which induce a persistent&#xD;
      local (gut) and systemic inflammation.The process is intensified by the intestinal generation&#xD;
      of several pro-inflammatory uremic toxins such as indoxyl sulfate, p-cresyl sulfate and&#xD;
      trimethyamine-N-oxide (2).The accumulation of these compounds correlates with systemic&#xD;
      inflammation, protein wasting and accelerated cardiovascular complications in hemodialysis&#xD;
      patients (3).&#xD;
&#xD;
      Short-chain fatty acids (SCFA) are produced in the colon and distal small intestine by&#xD;
      anaerobic bacteria following fermentation of complex carbohydrates. The 3 major compounds are&#xD;
      acetic acid, butyric and propionic acids. SCFA contribute to the health of the gut&#xD;
      (microbiome and mucosa) and the host. They have been shown to exert anti-inflammatory,&#xD;
      anti-cancer, antibacterial and antidiabetic effects. Lower values and an dysbiotic gut&#xD;
      contribute to various diseases such colitis, type 2 diabetes, rheumatoid disease and multiple&#xD;
      sclerosis. Supplementation of SCFA exerts anti-inflammatory actions both in intestinal&#xD;
      epithelial cells (5) and in the cardiovascular system (6). They also positively influence&#xD;
      auto- immune reactions /diseases (7, 8). In particular SCFA enhances formation of regulatory&#xD;
      T cells in the colon which are critical for regulating intestinal inflammation (15). Also&#xD;
      effector T cells such as Il-10 are implicated (16). Likewise SCFA are involved in the control&#xD;
      of body weight and insulin sensitivity (17), cholesterol synthesis (18) and retardation of&#xD;
      progressive CKD.&#xD;
&#xD;
      In patients on maintenance hemodialysis (MHD) a diet with a high fiber content, which favors&#xD;
      the intestinal SCFA formation (19), lowered the plasma levels of the colon-derived solutes&#xD;
      indoxyl sulfate and possibly p-cresol sulfate (20) and reduced inflammation, cardiovascular&#xD;
      diseases and all-cause mortality in CKD/ESRD patients (21). However, in ESRD consumption of a&#xD;
      fiber rich diet is limited due to the risk of hyperpotassemia. In addition the frequent&#xD;
      antibiotic therapy, application of phosphate binder or iron therapy alters the gut&#xD;
      microbiome.&#xD;
&#xD;
      The following mechanisms have been proposed for the actions of SCFA: the G-protein-coupled&#xD;
      receptors GPR 41 and GPR 43 (the free fatty acid receptors FFAR 3 and 2 ), GPR 109a, Olfr78 ,&#xD;
      the inhibition of histone deacetylases (HDAC) and stimulation of histone acetyltransferase&#xD;
      (HAT) activity (22, 23).&#xD;
&#xD;
      n this study we want to investigate in MHD patients whether a treatment with SCFA in form of&#xD;
      sodium propionate (SP) modulates the systemic inflammation, insulin resistance and&#xD;
      accumulation of intestinal uremic toxins. SP is chemically composed by a carboxylic acid&#xD;
      moiety and a small hydrocarbon chain with three carbon atoms (black balls), two oxygen (red&#xD;
      balls) and the white hydrogen atoms.&#xD;
&#xD;
      SP is involved in most effects of the short chain fatty acids including inhibition of&#xD;
      intestinal and hepatocyte lipid synthesis (24), lowering of fasting glycemia (25, 26) and&#xD;
      protection against diet-induced obesity ( 27). SP also regulates colonic T-reg cell&#xD;
      homeostasis (28) and exerts marked anti-inflammatory actions including intestinal epithelial&#xD;
      cells and macrophages (29) as well as in neutrophils, colon cells and colon cultures (30). It&#xD;
      improved experimental autoimmune encephalomyelitis (31) and experimental acute renal failure&#xD;
      (32). In addition antibacterial effects were documented (33, 34).&#xD;
&#xD;
      The patients under maintenance hemodialysis will receive the food additive sodium propionate&#xD;
      with a daily intake of 2 x 500 mg in form of capsules (Propicum) for 12 weeks. The&#xD;
      demographic information and the blood chemistry will be collected before the study, after 6,&#xD;
      12 and 16 weeks of drug administration.&#xD;
&#xD;
      The project will last for one year. The planned patient group should comprise of 15 patients&#xD;
      on maintenance hemodialysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">July 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of serum inflammatory biomarkers</measure>
    <time_frame>16 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of serum oxidative stress biomarkers</measure>
    <time_frame>16 weeks</time_frame>
    <description>glutathione peroxidase, malone dialdehyde</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of insulin resistance</measure>
    <time_frame>16 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of serum lipid levels</measure>
    <time_frame>16 weeks</time_frame>
    <description>Triglycerides, total cholesterol, high and low density cholesterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of hormonal parameter</measure>
    <time_frame>16 weeks</time_frame>
    <description>Leptin, resistin, adiponectin and glucagon-like peptide -1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of uremic toxins produced in the intestinal tract</measure>
    <time_frame>16 weeks</time_frame>
    <description>p-cresyl sulfate, indoxyl sulfate and trimethylamine -N-oxide</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of nutritional status</measure>
    <time_frame>16 weeks</time_frame>
    <description>Serum albumin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Variation from the beginning to the study end of parameters of well-being</measure>
    <time_frame>16 weeks</time_frame>
    <description>patient reported health (SF-36).</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Endstage Renal Disease</condition>
  <arm_group>
    <arm_group_label>Sodium propionate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sodium propionate will be administered with a daily intake of 2 x 500 mg in form of capsules for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sodium Propionate</intervention_name>
    <description>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.</description>
    <arm_group_label>Sodium propionate</arm_group_label>
    <other_name>Sodium propionate E281</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stable hemodialysis patients treated by renal replacement therapy for at least 6&#xD;
             months&#xD;
&#xD;
          -  Written informed consent written&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with malnutrition, infections, carcinoma, previous renal transplant,&#xD;
             intestinal diseases (medically diagnosed irritable bowel syndrome, Crohn's disease,&#xD;
             ulcerative colitis and diarrhea) and antibiotic treatment within one month of study&#xD;
             will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Biagio Di Iorio, Chief, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ASL AVELLINO</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Biagio Di Iorio, Chief, PhD</last_name>
    <phone>00390825530366</phone>
    <email>br.diiorio@gmail.com</email>
  </overall_contact>
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  </reference>
  <reference>
    <citation>Hung CC, Garner CD, Slauch JM, Dwyer ZW, Lawhon SD, Frye JG, McClelland M, Ahmer BM, Altier C. The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD. Mol Microbiol. 2013 Mar;87(5):1045-60. doi: 10.1111/mmi.12149. Epub 2013 Jan 28.</citation>
    <PMID>23289537</PMID>
  </reference>
  <reference>
    <citation>Sunkara LT, Jiang W, Zhang G. Modulation of antimicrobial host defense peptide gene expression by free fatty acids. PLoS One. 2012;7(11):e49558. doi: 10.1371/journal.pone.0049558. Epub 2012 Nov 15.</citation>
    <PMID>23166711</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>November 28, 2016</last_update_submitted>
  <last_update_submitted_qc>November 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Sanitaria ASL Avellino 2</investigator_affiliation>
    <investigator_full_name>Dr Biagio Di Iorio</investigator_full_name>
    <investigator_title>Dr, Chief Nephrology Division</investigator_title>
  </responsible_party>
  <keyword>Endstage renal Disease</keyword>
  <keyword>Hemodialysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02976688
org study id: ASL AVELLINO
nct id: NCT02976688
lead sponsor: 
has dmc: No
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.
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.
      Important promoters of these obstacles are enhanced generation of reactive oxygen species
      (ROS), systemic inflammation, acquired immunodeficiency (9, 10) and an impaired glucose and
      insulin homeostasis (11).

      Systemic inflammation and oxidative stress in ESRD are induced by activation of the innate
      immune system involving monocytes, macrophages, granulocytes and cellular constituents
      (endothelial cell activation) as well as depletion of natural regulatory T cells that impairs
      their ability to suppress inflammation .The concomitant reduced humoral immunity is favored
      by depletion of antigen presenting dendritic cells, a lowered CD44/CD8 T cell ratio,
      depletion of naïve and central memory T cells, diffuse B cell lymphopenia and an impaired
      phagocytic ability of monocytes and PMNs (12).

      Insulin resistance (IR) participates in the pathogenesis of multiple metabolic and
      cardiovascular disturbances (13) and is an important factor of the accelerated muscle protein
      degradation in ESRD (14). Underlying mechanisms of IR are the metabolic inflammation, in
      particular elevated LPS levels.

      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 (Fig.2). The passage includes whole bacteria
      (going into mesenteric lymph nodes), endotoxins/ lipoproteinlipase (LPS) (cell wall
      components of the bacteria) and other noxious luminal products which induce a persistent
      local (gut) and systemic inflammation.The process is intensified by the intestinal generation
      of several pro-inflammatory uremic toxins such as indoxyl sulfate, p-cresyl sulfate and
      trimethyamine-N-oxide (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. The 3 major compounds are
      acetic acid, butyric and propionic acids. SCFA contribute to the health of the gut
      (microbiome and mucosa) and the host. They have been shown to exert anti-inflammatory,
      anti-cancer, antibacterial and antidiabetic effects. Lower values and an dysbiotic gut
      contribute to various diseases such colitis, type 2 diabetes, rheumatoid disease and multiple
      sclerosis. 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 particular SCFA enhances formation of regulatory
      T cells in the colon which are critical for regulating intestinal inflammation (15). Also
      effector T cells such as Il-10 are implicated (16). Likewise SCFA are involved in the control
      of body weight and insulin sensitivity (17), cholesterol synthesis (18) and retardation of
      progressive CKD.

      In patients on maintenance hemodialysis (MHD) a diet with a high fiber content, which favors
      the intestinal SCFA formation (19), lowered the plasma levels of the colon-derived solutes
      indoxyl sulfate and possibly p-cresol sulfate (20) and reduced inflammation, cardiovascular
      diseases and all-cause mortality in CKD/ESRD patients (21). However, in ESRD consumption of a
      fiber rich diet is limited due to the risk of hyperpotassemia. In addition the frequent
      antibiotic therapy, application of phosphate binder or iron therapy alters the gut
      microbiome.

      The following mechanisms have been proposed for the actions of SCFA: the G-protein-coupled
      receptors GPR 41 and GPR 43 (the free fatty acid receptors FFAR 3 and 2 ), GPR 109a, Olfr78 ,
      the inhibition of histone deacetylases (HDAC) and stimulation of histone acetyltransferase
      (HAT) activity (22, 23).

      n 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. SP is chemically composed by a carboxylic acid
      moiety and a small hydrocarbon chain with three carbon atoms (black balls), two oxygen (red
      balls) and the white hydrogen atoms.

      SP is involved in most effects of the short chain fatty acids including inhibition of
      intestinal and hepatocyte lipid synthesis (24), lowering of fasting glycemia (25, 26) and
      protection against diet-induced obesity ( 27). SP also regulates colonic T-reg cell
      homeostasis (28) and exerts marked anti-inflammatory actions including intestinal epithelial
      cells and macrophages (29) as well as in neutrophils, colon cells and colon cultures (30). It
      improved experimental autoimmune encephalomyelitis (31) and experimental acute renal failure
      (32). In addition antibacterial effects were documented (33, 34).

      The patients under maintenance hemodialysis will receive the food additive sodium propionate
      with a daily intake of 2 x 500 mg in form of capsules (Propicum) for 12 weeks. The
      demographic information and the blood chemistry will be collected before the study, after 6,
      12 and 16 weeks of drug administration.

      The project will last for one year. The planned patient group should comprise of 15 patients
      on maintenance hemodialysis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Variation from the beginning to the study end of serum inflammatory biomarkers
time frame: 16 weeks
description: 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.
measure: Variation from the beginning to the study end of serum oxidative stress biomarkers
time frame: 16 weeks
description: glutathione peroxidase, malone dialdehyde
measure: Variation from the beginning to the study end of insulin resistance
time frame: 16 weeks
description: 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.
measure: Variation from the beginning to the study end of serum lipid levels
time frame: 16 weeks
description: Triglycerides, total cholesterol, high and low density cholesterol
measure: Variation from the beginning to the study end of hormonal parameter
time frame: 16 weeks
description: Leptin, resistin, adiponectin and glucagon-like peptide -1.
measure: Variation from the beginning to the study end of uremic toxins produced in the intestinal tract
time frame: 16 weeks
description: p-cresyl sulfate, indoxyl sulfate and trimethylamine -N-oxide
measure: Variation from the beginning to the study end of nutritional status
time frame: 16 weeks
description: Serum albumin
measure: Variation from the beginning to the study end of parameters of well-being
time frame: 16 weeks
description: patient reported health (SF-36).
arm group label: Sodium propionate
arm group type: Experimental
description: Sodium propionate will be administered with a daily intake of 2 x 500 mg in form of capsules for 12 weeks.
intervention type: Other
intervention name: Sodium Propionate
description: 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.
arm group label: Sodium propionate
other name: Sodium propionate E281
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Biagio Di Iorio, Chief, PhD
role: Principal Investigator
affiliation: ASL AVELLINO
last name: Biagio Di Iorio, Chief, PhD
phone: 00390825530366
email: br.diiorio@gmail.com
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citation: Hung CC, Garner CD, Slauch JM, Dwyer ZW, Lawhon SD, Frye JG, McClelland M, Ahmer BM, Altier C. The intestinal fatty acid propionate inhibits Salmonella invasion through the post-translational control of HilD. Mol Microbiol. 2013 Mar;87(5):1045-60. doi: 10.1111/mmi.12149. Epub 2013 Jan 28.
PMID: 23289537
citation: Sunkara LT, Jiang W, Zhang G. Modulation of antimicrobial host defense peptide gene expression by free fatty acids. PLoS One. 2012;7(11):e49558. doi: 10.1371/journal.pone.0049558. Epub 2012 Nov 15.
PMID: 23166711
responsible party type: Principal Investigator
investigator affiliation: Azienda Sanitaria ASL Avellino 2
investigator full name: Dr Biagio Di Iorio
investigator title: Dr, Chief Nephrology Division
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
sharing ipd: No