<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/NCT01733017</url>
  </required_header>
  <id_info>
    <org_study_id>R01NR013430</org_study_id>
    <nct_id>NCT01733017</nct_id>
  </id_info>
  <brief_title>Nutrition Intervention to Decrease Symptoms in Patients With Heart Failure</brief_title>
  <acronym>NIHFT</acronym>
  <official_title>Nutrition Intervention to Reduce Symptoms in Patients With Advanced Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Terry Lennie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of is to test the effects of a 6-month nutrition intervention of dietary sodium&#xD;
      reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure&#xD;
      symptoms, health-related quality of life, and time to heart failure rehospitalization or&#xD;
      all-cause death.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For a majority of patients with advanced heart failure, medical treatment is only partially&#xD;
      effective in relieving heart failure symptoms. Therefore, it is recommended that palliative&#xD;
      care be initiated soon after diagnosis. There is a need for complementary, nonpharmacologic&#xD;
      interventions that could be easily implemented by health care providers to provide palliative&#xD;
      care. Three major pathologic pathways underlying heart failure symptoms have been identified:&#xD;
      fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that&#xD;
      three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic&#xD;
      pathways. Clinical trials to date have only tested each nutrient individually. There is&#xD;
      strong theoretical rationale that a combined intervention targeting all three nutrients would&#xD;
      have substantial benefit in relieving symptoms in advanced heart failure. Therefore, the&#xD;
      purposes of this study are to test the effects of a 6-month nutrition intervention of dietary&#xD;
      sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart&#xD;
      failure symptoms, health-related quality of life, and time to heart failure rehospitalization&#xD;
      or all-cause death. The aims of this placebo controlled study are 1) to determine the effects&#xD;
      of a 6-month nutrition intervention on symptom burden (edema, shortness of air, and fatigue)&#xD;
      and health related quality of life at 3 and 6 months, and time to heart failure&#xD;
      rehospitalization or all-cause death over 12 months from baseline; 2) compare dietary sodium&#xD;
      intake, inflammation, and markers of oxidative stress between the nutrition intervention&#xD;
      group and a placebo group at 3 and 6 months; and 3) compare body weight, serum lycopene, and&#xD;
      erythrocyte omega-3 index between the nutrition intervention group and a placebo group at 3&#xD;
      and 6 months. A total of 150 patients with advanced heart failure will be randomized to&#xD;
      either the nutrition intervention or placebo group (75 per group). The nutrition intervention&#xD;
      group will receive a theory based education and skill building intervention designed to&#xD;
      decrease dietary sodium intake to ~2 g per day. A research nurse will make 4 home visits and&#xD;
      one follow-up telephone call over 6 months to provide the education-skill building&#xD;
      intervention. The intervention group will take 3 omega-3 fatty acid capsules (350 mg&#xD;
      eicosapentaenoic acid and 50 mg docosahexaenoic acid) and consume tomato juice or other&#xD;
      tomato-based products containing 20-25 mg of lycopene daily for six months. The placebo group&#xD;
      will receive the same number of visits and phone calls but only general nutrition information&#xD;
      will be provided. They will take 3 placebo capsules containing rice oil (500 mg/capsule) and&#xD;
      consume their choice of fruit juices that do not contain lycopene daily for six months. Data&#xD;
      will be collected in person at baseline, 3 months, and 6 months by a research assistant&#xD;
      blinded to the group assignment. Patients will be followed for an additional 6 months by&#xD;
      telephone to collect longer term data on symptom burden and quality of life as well as heart&#xD;
      failure hospitalization and all-cause mortality at 9 and 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2011</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event-Free Survival</measure>
    <time_frame>12 months</time_frame>
    <description>Combined endpoint of cardiac-related hospitalization and all cause mortality</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Symptom burden</measure>
    <time_frame>baseline, 3, 6, 9, and 12 months</time_frame>
    <description>combined score of symptom severity, frequency, and distress for common symptoms of heart failure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quality of life</measure>
    <time_frame>baseline, 3, 6, 9, 12 months</time_frame>
    <description>heart failure related quality of life</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>omega-3 index</measure>
    <time_frame>baseline, 3, 6, 9, 12 months</time_frame>
    <description>the ratio of EPA plus DHA as a percentage of total fatty acids in the cell membrane of erythrocytes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>oxidative stress</measure>
    <time_frame>baseline, 3, 6, 9, 12 months</time_frame>
    <description>serum levels of malondialdehyde and 8-iso-PGF2a isoprostane will serve as markers of increased lipid peroxidation due to oxygen free radical production exceeding antioxidant capacity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation</measure>
    <time_frame>baseline, 3, 6, 9, 12 months</time_frame>
    <description>Serum levels of tumor necrosis factor-alpha (TNFα), soluble TNF receptors: sTNFR1 and sTNFR2 will be measured as markers of proinflammatory cytokine activity; interleukin-10 (IL-10) will be measured as a marker of anti-inflammatory cytokine activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lycopene</measure>
    <time_frame>baseline, 3, 6, 9, 12 months</time_frame>
    <description>Plasma lycopene will be measured as a marker intervention effectiveness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sodium intake</measure>
    <time_frame>baseline, 3, 6, 9, 12 months</time_frame>
    <description>Three 24-hour diet recall interviews at each timepoint will be used estimate sodium intake and to identify high sodium foods and eating patterns for the sodium reduction component of the intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>sodium reduction, omega-3, lycopene</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>combination of dietary sodium restriction with supplementation of omega-3 capsules and lycopene containing juices or foods</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Limited nutritional counseling, juice without lycopene, rice oil capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Sodium reduction</intervention_name>
    <description>Teaching and skill building to reduce dietary sodium</description>
    <arm_group_label>sodium reduction, omega-3, lycopene</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>omega 3 and lycopene supplements</intervention_name>
    <description>omega-3 fatty acid supplements and juices containing lycopene</description>
    <arm_group_label>sodium reduction, omega-3, lycopene</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>rice bran oil capsules</intervention_name>
    <description>placebo capsules</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Generic dietary feedback from</intervention_name>
    <description>Provided a summary of the 3 day dietary recalls at baseline, 3 months, and 6 months</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>attention control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  chronic heart failure with either preserved or non-preserved ejection fraction&#xD;
&#xD;
          -  for chronic heart failure, have undergone evaluation of heart failure and optimization&#xD;
             of medical therapy, for patients discharged from hospital for acute/newly diagnosed&#xD;
             heart failure, have undergone evaluation of heart failure and optimization of medical&#xD;
             therapy for at least 1 month post discharge&#xD;
&#xD;
          -  New York Heart Association functional classification of II, III or IV&#xD;
&#xD;
          -  have not been referred for heart transplantation&#xD;
&#xD;
          -  able to read and speak English&#xD;
&#xD;
          -  no cognitive impairment that precludes giving informed consent or ability to follow&#xD;
             protocol instruction.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &lt; 17 kg/m2 or &gt; 46 kg/m2&#xD;
&#xD;
          -  co-existing illness documented in the medical record known to be associated with&#xD;
             systemic inflammation decreased appetite or absorption, fatigue, edema, or weight loss&#xD;
&#xD;
          -  currently taking dietary supplements that contain lycopene or omega-3 fatty acids&#xD;
&#xD;
          -  allergy to rice bran oil&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Terry A Lennie, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky College of Nursing</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky, College of Nursing</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536-0232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Health Care</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <last_update_submitted>March 15, 2017</last_update_submitted>
  <last_update_submitted_qc>March 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Terry Lennie</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>heart failure</keyword>
  <keyword>nutrition therapy</keyword>
  <keyword>symptoms</keyword>
  <keyword>quality of life</keyword>
  <keyword>lycopene</keyword>
  <keyword>omega-3 fatty acids</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lycopene</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01733017
org study id: R01NR013430
nct id: NCT01733017
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of is to test the effects of a 6-month nutrition intervention of dietary sodium
      reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure
      symptoms, health-related quality of life, and time to heart failure rehospitalization or
      all-cause death.
For a majority of patients with advanced heart failure, medical treatment is only partially
      effective in relieving heart failure symptoms. Therefore, it is recommended that palliative
      care be initiated soon after diagnosis. There is a need for complementary, nonpharmacologic
      interventions that could be easily implemented by health care providers to provide palliative
      care. Three major pathologic pathways underlying heart failure symptoms have been identified:
      fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that
      three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic
      pathways. Clinical trials to date have only tested each nutrient individually. There is
      strong theoretical rationale that a combined intervention targeting all three nutrients would
      have substantial benefit in relieving symptoms in advanced heart failure. Therefore, the
      purposes of this study are to test the effects of a 6-month nutrition intervention of dietary
      sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart
      failure symptoms, health-related quality of life, and time to heart failure rehospitalization
      or all-cause death. The aims of this placebo controlled study are 1) to determine the effects
      of a 6-month nutrition intervention on symptom burden (edema, shortness of air, and fatigue)
      and health related quality of life at 3 and 6 months, and time to heart failure
      rehospitalization or all-cause death over 12 months from baseline; 2) compare dietary sodium
      intake, inflammation, and markers of oxidative stress between the nutrition intervention
      group and a placebo group at 3 and 6 months; and 3) compare body weight, serum lycopene, and
      erythrocyte omega-3 index between the nutrition intervention group and a placebo group at 3
      and 6 months. A total of 150 patients with advanced heart failure will be randomized to
      either the nutrition intervention or placebo group (75 per group). The nutrition intervention
      group will receive a theory based education and skill building intervention designed to
      decrease dietary sodium intake to ~2 g per day. A research nurse will make 4 home visits and
      one follow-up telephone call over 6 months to provide the education-skill building
      intervention. The intervention group will take 3 omega-3 fatty acid capsules (350 mg
      eicosapentaenoic acid and 50 mg docosahexaenoic acid) and consume tomato juice or other
      tomato-based products containing 20-25 mg of lycopene daily for six months. The placebo group
      will receive the same number of visits and phone calls but only general nutrition information
      will be provided. They will take 3 placebo capsules containing rice oil (500 mg/capsule) and
      consume their choice of fruit juices that do not contain lycopene daily for six months. Data
      will be collected in person at baseline, 3 months, and 6 months by a research assistant
      blinded to the group assignment. Patients will be followed for an additional 6 months by
      telephone to collect longer term data on symptom burden and quality of life as well as heart
      failure hospitalization and all-cause mortality at 9 and 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Event-Free Survival
time frame: 12 months
description: Combined endpoint of cardiac-related hospitalization and all cause mortality
measure: Symptom burden
time frame: baseline, 3, 6, 9, and 12 months
description: combined score of symptom severity, frequency, and distress for common symptoms of heart failure
measure: Quality of life
time frame: baseline, 3, 6, 9, 12 months
description: heart failure related quality of life
measure: omega-3 index
time frame: baseline, 3, 6, 9, 12 months
description: the ratio of EPA plus DHA as a percentage of total fatty acids in the cell membrane of erythrocytes
measure: oxidative stress
time frame: baseline, 3, 6, 9, 12 months
description: serum levels of malondialdehyde and 8-iso-PGF2a isoprostane will serve as markers of increased lipid peroxidation due to oxygen free radical production exceeding antioxidant capacity
measure: Inflammation
time frame: baseline, 3, 6, 9, 12 months
description: Serum levels of tumor necrosis factor-alpha (TNFα), soluble TNF receptors: sTNFR1 and sTNFR2 will be measured as markers of proinflammatory cytokine activity; interleukin-10 (IL-10) will be measured as a marker of anti-inflammatory cytokine activity
measure: Lycopene
time frame: baseline, 3, 6, 9, 12 months
description: Plasma lycopene will be measured as a marker intervention effectiveness
measure: Sodium intake
time frame: baseline, 3, 6, 9, 12 months
description: Three 24-hour diet recall interviews at each timepoint will be used estimate sodium intake and to identify high sodium foods and eating patterns for the sodium reduction component of the intervention.
arm group label: sodium reduction, omega-3, lycopene
arm group type: Experimental
description: combination of dietary sodium restriction with supplementation of omega-3 capsules and lycopene containing juices or foods
arm group label: Control
arm group type: Placebo Comparator
description: Limited nutritional counseling, juice without lycopene, rice oil capsules
intervention type: Behavioral
intervention name: Sodium reduction
description: Teaching and skill building to reduce dietary sodium
arm group label: sodium reduction, omega-3, lycopene
intervention type: Dietary Supplement
intervention name: omega 3 and lycopene supplements
description: omega-3 fatty acid supplements and juices containing lycopene
arm group label: sodium reduction, omega-3, lycopene
intervention type: Dietary Supplement
intervention name: rice bran oil capsules
description: placebo capsules
arm group label: Control
other name: placebo
intervention type: Behavioral
intervention name: Generic dietary feedback from
description: Provided a summary of the 3 day dietary recalls at baseline, 3 months, and 6 months
arm group label: Control
other name: attention control
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Terry A Lennie, PhD
role: Principal Investigator
affiliation: University of Kentucky College of Nursing
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Terry Lennie
investigator title: PI
mesh term: Heart Failure
mesh term: Lycopene