<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/NCT04505462</url>
  </required_header>
  <id_info>
    <org_study_id>FEMH-IRB-109112-F</org_study_id>
    <nct_id>NCT04505462</nct_id>
  </id_info>
  <brief_title>Dietary Therapy in Dialysis Patients</brief_title>
  <official_title>Short-Term Effects of Therapeutic Diet in Dialysis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Far Eastern Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Far Eastern Memorial Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with end-stage kidney disease have hyperphosphatemia and accumulated uremic toxin&#xD;
      level due to decreased urine excretion ability. Unhealthy diet causes altered mineral&#xD;
      metabolism, elevated uremic toxin level, immune dysregulation, and inflammation. The&#xD;
      investigators hypothesize that therapeutic diet intervention reverses altered mineral&#xD;
      metabolism, elevated uremic toxin level, immune dysregulation, and inflammation. In this&#xD;
      study, the investigators crafted 7-day special healthy diet to illustrate the clinical&#xD;
      implications of therapeutic diet for dialysis patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The risk of cardiovascular disease (CVD) and mortality in patients with end-stage kidney&#xD;
      disease (ESKD) is far greater than those in the general population. Emerging evidence&#xD;
      suggests that unhealthy diet causes altered mineral metabolism, disturbance of gut microbiota&#xD;
      (dysbiosis) with elevated uremic toxin level, immune dysregulation, and inflammation; these&#xD;
      abnormalities are strongly related to development of CVD. Little is known about the&#xD;
      relationship between therapeutic diet intervention and cardiovascular risk in patients with&#xD;
      ESKD. Recently, the study of the investigators showed that ESKD patients undergoing&#xD;
      hemodialysis who consumed very low-phosphate diet, phosphate-to-protein ratio (PPR) value of&#xD;
      8 mg/g, experienced an extra reduction of serum phosphorus level by 0.61 mg/dL compared with&#xD;
      that of low-phosphate diet, PPR value of 10 mg/g.&#xD;
&#xD;
      The aim of the study is to explore the effect of 7-day therapeutic diet intervention on&#xD;
      changes of altered mineral metabolism, uremic toxin production, immune dysregulation and&#xD;
      inflammation, highlighting the important role of dietary modification in dialysis population.&#xD;
&#xD;
      It is to conduct a randomized controlled trial with cross-over design at a hemodialysis unit&#xD;
      of tertiary teaching hospital in Northern Taiwan. Subjects with aged older than 20 years,&#xD;
      ESKD undergoing maintenance dialysis for more than three months, having adequate dialysis and&#xD;
      serum intact parathyroid hormone less than 800 pg/mL will be included. Participants will be&#xD;
      randomly assigned into two groups: those in group A will receive study diet for 7 days,&#xD;
      followed by 4-week washout period and then receive 7-day usual diet. The opposite order of&#xD;
      diets will be prescribed in group B. The study meals are prepared in the hospital cafeteria.&#xD;
      Dietary compositions of the study diets were analyzed before the start of the study. The&#xD;
      study outcome measures are difference in change-from-baseline values of altered mineral&#xD;
      metabolism, uremic toxin production, immune dysregulation and inflammation between the&#xD;
      therapeutic diet and the usual diet.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 28, 2020</start_date>
  <completion_date type="Actual">March 1, 2022</completion_date>
  <primary_completion_date type="Actual">December 10, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>A randomized, active-controlled trial with cross-over design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Laboratory technicians who assess the study outcomes will be masked</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Concentrations of intact fibroblast growth factor 23 (pg/mL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline intact fibroblast growth factor 23 (pg/mL) between therapeutic diet and usual diet</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentrations of C-terminal fibroblast growth factor 23 (RU/mL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline C-terminal fibroblast growth factor 23 (RU/mL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of phosphate (mg/dL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline phosphate (mg/dL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of calcium (mg/dL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline calcium (mg/dL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of intact parathyroid hormone (pg/mL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline intact parathyroid hormone (pg/mL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of free indoxyl sulfate (mg/L)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline free indoxyl sulfate (mg/L) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of free p-cresol sulfate (mg/L)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline free p-cresol sulfate (mg/L) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of pre-albumin (g/dL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline pre-albumin (g/dL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of albumin (g/dL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline albumin (g/dL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentrations of C-reactive protein (mg/dL)</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline C-reactive protein (mg/dL) between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute number (per μl blood) of CD4+ (cluster of differentiation 4) T cells</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline absolute number (per μl blood) of CD4+ T cells between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute number (per μl blood) of CD8+ (cluster of differentiation 8) T cells</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline absolute number (per μl blood) of CD8+ T cells between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute number (per μl blood) of monocytes</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline absolute number (per μl blood) of monocytes between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage (%) of CD4+ (cluster of differentiation 4) T cells</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline percentage (%) of CD4+ (cluster of differentiation 4) T cells between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage (%) of CD8+ (cluster of differentiation 8) T cells</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline percentage (%) of CD8+ (cluster of differentiation 8) T cells between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage (%) of monocytes</measure>
    <time_frame>7 days</time_frame>
    <description>Difference in change-from-baseline percentage (%) of monocytes between therapeutic diet and usual diet</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>End Stage Renal Disease on Dialysis</condition>
  <arm_group>
    <arm_group_label>Study diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>7-day therapeutic diet intervention as experimental group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual diet</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>7-day usual diet as control group, no dietary intervention in this group, participants consumed their habitual diet</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Therapeutic diet</intervention_name>
    <description>A special healthy diet for dialysis patients</description>
    <arm_group_label>Study diet</arm_group_label>
    <other_name>Dietary therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with aged older than 20 years, ESKD undergoing maintenance dialysis for more&#xD;
             than three months, having adequate dialysis, serum intact parathyroid hormone less&#xD;
             than 800 pg/mL and good dietary compliance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who meet any of the following criteria will be excluded from the study:&#xD;
&#xD;
               1. Serum albumin level less than 2.5 g/dL&#xD;
&#xD;
               2. Hospitalization within the past 4 weeks&#xD;
&#xD;
               3. Prebiotics, probiotics, symbiotics or antibiotics use within the past 4 weeks&#xD;
&#xD;
               4. History of psychiatric disorders&#xD;
&#xD;
               5. Having mental retardation&#xD;
&#xD;
               6. Those who dislike of the study meals&#xD;
&#xD;
               7. Soft diet requirement&#xD;
&#xD;
               8. Vegetarian&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wan-Chuan Tsai, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Far Eastern Memorial Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Far Eastern Memorial Hospital</name>
      <address>
        <city>New Taipei City</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Tsai WC, Wu HY, Peng YS, Hsu SP, Chiu YL, Yang JY, Chen HY, Pai MF, Lin WY, Hung KY, Chu FY, Tsai SM, Chien KL. Short-Term Effects of Very-Low-Phosphate and Low-Phosphate Diets on Fibroblast Growth Factor 23 in Hemodialysis Patients: A Randomized Crossover Trial. Clin J Am Soc Nephrol. 2019 Oct 7;14(10):1475-1483. doi: 10.2215/CJN.04250419. Epub 2019 Sep 13.</citation>
    <PMID>31519550</PMID>
  </reference>
  <reference>
    <citation>Tsai WC, Wu HY, Peng YS, Hsu SP, Chiu YL, Chen HY, Yang JY, Ko MJ, Pai MF, Tu YK, Hung KY, Chien KL. Effects of lower versus higher phosphate diets on fibroblast growth factor-23 levels in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018 Nov 1;33(11):1977-1983. doi: 10.1093/ndt/gfy005.</citation>
    <PMID>29420827</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Far Eastern Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Wan-Chuan Tsai</investigator_full_name>
    <investigator_title>Principal Investigator, Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Therapeutic diet</keyword>
  <keyword>Mineral metabolism</keyword>
  <keyword>Uremic toxins</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Immune</keyword>
  <keyword>End-stage kidney disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual-level deidentified participant data will be made available by the corresponding author of the paper upon request by email. The data will be available for 3 years after formal publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>The data will become available after completing the study for 1 year and for 3 years after formal publication.</ipd_time_frame>
    <ipd_access_criteria>Data will be made available by the corresponding author of the paper upon request by email.</ipd_access_criteria>
  </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/NCT04505462
org study id: FEMH-IRB-109112-F
nct id: NCT04505462
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with end-stage kidney disease have hyperphosphatemia and accumulated uremic toxin
      level due to decreased urine excretion ability. Unhealthy diet causes altered mineral
      metabolism, elevated uremic toxin level, immune dysregulation, and inflammation. The
      investigators hypothesize that therapeutic diet intervention reverses altered mineral
      metabolism, elevated uremic toxin level, immune dysregulation, and inflammation. In this
      study, the investigators crafted 7-day special healthy diet to illustrate the clinical
      implications of therapeutic diet for dialysis patients.
The risk of cardiovascular disease (CVD) and mortality in patients with end-stage kidney
      disease (ESKD) is far greater than those in the general population. Emerging evidence
      suggests that unhealthy diet causes altered mineral metabolism, disturbance of gut microbiota
      (dysbiosis) with elevated uremic toxin level, immune dysregulation, and inflammation; these
      abnormalities are strongly related to development of CVD. Little is known about the
      relationship between therapeutic diet intervention and cardiovascular risk in patients with
      ESKD. Recently, the study of the investigators showed that ESKD patients undergoing
      hemodialysis who consumed very low-phosphate diet, phosphate-to-protein ratio (PPR) value of
      8 mg/g, experienced an extra reduction of serum phosphorus level by 0.61 mg/dL compared with
      that of low-phosphate diet, PPR value of 10 mg/g.

      The aim of the study is to explore the effect of 7-day therapeutic diet intervention on
      changes of altered mineral metabolism, uremic toxin production, immune dysregulation and
      inflammation, highlighting the important role of dietary modification in dialysis population.

      It is to conduct a randomized controlled trial with cross-over design at a hemodialysis unit
      of tertiary teaching hospital in Northern Taiwan. Subjects with aged older than 20 years,
      ESKD undergoing maintenance dialysis for more than three months, having adequate dialysis and
      serum intact parathyroid hormone less than 800 pg/mL will be included. Participants will be
      randomly assigned into two groups: those in group A will receive study diet for 7 days,
      followed by 4-week washout period and then receive 7-day usual diet. The opposite order of
      diets will be prescribed in group B. The study meals are prepared in the hospital cafeteria.
      Dietary compositions of the study diets were analyzed before the start of the study. The
      study outcome measures are difference in change-from-baseline values of altered mineral
      metabolism, uremic toxin production, immune dysregulation and inflammation between the
      therapeutic diet and the usual diet.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: A randomized, active-controlled trial with cross-over design
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Laboratory technicians who assess the study outcomes will be masked
measure: Concentrations of intact fibroblast growth factor 23 (pg/mL)
time frame: 7 days
description: Difference in change-from-baseline intact fibroblast growth factor 23 (pg/mL) between therapeutic diet and usual diet
measure: Concentrations of C-terminal fibroblast growth factor 23 (RU/mL)
time frame: 7 days
description: Difference in change-from-baseline C-terminal fibroblast growth factor 23 (RU/mL) between therapeutic diet and usual diet
measure: Concentrations of phosphate (mg/dL)
time frame: 7 days
description: Difference in change-from-baseline phosphate (mg/dL) between therapeutic diet and usual diet
measure: Concentrations of calcium (mg/dL)
time frame: 7 days
description: Difference in change-from-baseline calcium (mg/dL) between therapeutic diet and usual diet
measure: Concentrations of intact parathyroid hormone (pg/mL)
time frame: 7 days
description: Difference in change-from-baseline intact parathyroid hormone (pg/mL) between therapeutic diet and usual diet
measure: Concentrations of free indoxyl sulfate (mg/L)
time frame: 7 days
description: Difference in change-from-baseline free indoxyl sulfate (mg/L) between therapeutic diet and usual diet
measure: Concentrations of free p-cresol sulfate (mg/L)
time frame: 7 days
description: Difference in change-from-baseline free p-cresol sulfate (mg/L) between therapeutic diet and usual diet
measure: Concentrations of pre-albumin (g/dL)
time frame: 7 days
description: Difference in change-from-baseline pre-albumin (g/dL) between therapeutic diet and usual diet
measure: Concentrations of albumin (g/dL)
time frame: 7 days
description: Difference in change-from-baseline albumin (g/dL) between therapeutic diet and usual diet
measure: Concentrations of C-reactive protein (mg/dL)
time frame: 7 days
description: Difference in change-from-baseline C-reactive protein (mg/dL) between therapeutic diet and usual diet
measure: Absolute number (per μl blood) of CD4+ (cluster of differentiation 4) T cells
time frame: 7 days
description: Difference in change-from-baseline absolute number (per μl blood) of CD4+ T cells between therapeutic diet and usual diet
measure: Absolute number (per μl blood) of CD8+ (cluster of differentiation 8) T cells
time frame: 7 days
description: Difference in change-from-baseline absolute number (per μl blood) of CD8+ T cells between therapeutic diet and usual diet
measure: Absolute number (per μl blood) of monocytes
time frame: 7 days
description: Difference in change-from-baseline absolute number (per μl blood) of monocytes between therapeutic diet and usual diet
measure: Percentage (%) of CD4+ (cluster of differentiation 4) T cells
time frame: 7 days
description: Difference in change-from-baseline percentage (%) of CD4+ (cluster of differentiation 4) T cells between therapeutic diet and usual diet
measure: Percentage (%) of CD8+ (cluster of differentiation 8) T cells
time frame: 7 days
description: Difference in change-from-baseline percentage (%) of CD8+ (cluster of differentiation 8) T cells between therapeutic diet and usual diet
measure: Percentage (%) of monocytes
time frame: 7 days
description: Difference in change-from-baseline percentage (%) of monocytes between therapeutic diet and usual diet
arm group label: Study diet
arm group type: Experimental
description: 7-day therapeutic diet intervention as experimental group
arm group label: Usual diet
arm group type: No Intervention
description: 7-day usual diet as control group, no dietary intervention in this group, participants consumed their habitual diet
intervention type: Other
intervention name: Therapeutic diet
description: A special healthy diet for dialysis patients
arm group label: Study diet
other name: Dietary therapy
criteria: 
gender: All
minimum age: 21 Years
maximum age: 99 Years
healthy volunteers: No
last name: Wan-Chuan Tsai, M.D., Ph.D.
role: Principal Investigator
affiliation: Far Eastern Memorial Hospital
facility: 
country: Taiwan
citation: Tsai WC, Wu HY, Peng YS, Hsu SP, Chiu YL, Yang JY, Chen HY, Pai MF, Lin WY, Hung KY, Chu FY, Tsai SM, Chien KL. Short-Term Effects of Very-Low-Phosphate and Low-Phosphate Diets on Fibroblast Growth Factor 23 in Hemodialysis Patients: A Randomized Crossover Trial. Clin J Am Soc Nephrol. 2019 Oct 7;14(10):1475-1483. doi: 10.2215/CJN.04250419. Epub 2019 Sep 13.
PMID: 31519550
citation: Tsai WC, Wu HY, Peng YS, Hsu SP, Chiu YL, Chen HY, Yang JY, Ko MJ, Pai MF, Tu YK, Hung KY, Chien KL. Effects of lower versus higher phosphate diets on fibroblast growth factor-23 levels in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018 Nov 1;33(11):1977-1983. doi: 10.1093/ndt/gfy005.
PMID: 29420827
responsible party type: Principal Investigator
investigator affiliation: Far Eastern Memorial Hospital
investigator full name: Wan-Chuan Tsai
investigator title: Principal Investigator, Assistant Professor
mesh term: Kidney Failure, Chronic
sharing ipd: Yes
ipd description: Individual-level deidentified participant data will be made available by the corresponding author of the paper upon request by email. The data will be available for 3 years after formal publication.
ipd info type: Study Protocol
ipd time frame: The data will become available after completing the study for 1 year and for 3 years after formal publication.
ipd access criteria: Data will be made available by the corresponding author of the paper upon request by email.