<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/NCT02201758</url>
  </required_header>
  <id_info>
    <org_study_id>Bio 14-128</org_study_id>
    <nct_id>NCT02201758</nct_id>
  </id_info>
  <brief_title>Flaxseed Lignan-Enriched Complex (FLC) for the Treatment of Patients With Ulcerative Colitis (UC): A Pilot Assessment</brief_title>
  <acronym>FLC&amp;UC</acronym>
  <official_title>Flaxseed Lignan-enriched Complex (FLC) for the Treatment of Patients With Mild to Moderately Severe Ulcerative Colitis (UC): A Pilot Assessment.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Saskatchewan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Royal University Hospital Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Saskatchewan</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study proposes to examine the effect of diet as a modifiable risk factor among patients&#xD;
      with ulcerative colitis (UC). Flax seeds contain many bioactive constituents which have&#xD;
      anti-oxidative, anti-inflammatory, and anti-carcinogenic effects. These bioactive compounds&#xD;
      represent novel classes of pharmacologically active compounds which may represent new options&#xD;
      to treat chronic disease of the gastrointestinal tract. Participants with mild to moderately&#xD;
      severe UC will supplement their current medications with flaxseed lignan-enriched complex&#xD;
      (FLC). This is a 12 week double blind placebo controlled study with assessment throughout.&#xD;
      Stool and blood samples (biomarkers) as well as bowel assessment via sigmoidoscopy will be&#xD;
      evaluated before and after the intervention. The treatment arm consists of 300 mg FLC taken&#xD;
      orally twice daily.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This project is a single centre, randomized, placebo-controlled pilot study in which subjects&#xD;
      recruited to the study will undergo treatment with FLC for an 8-week period. The&#xD;
      investigators will recruit patients with mild to moderately severe, left-sided or pan-colonic&#xD;
      UC (Mayo Score 3 - 10 points). All participants will have vitamin D status evaluated at&#xD;
      baseline and clinically indicated laboratory investigations including complete blood count&#xD;
      (CBC), liver enzymes and serologic inflammatory marker high sensitivity c-reactive protein&#xD;
      (hsCRP). Participants will be evaluated at weeks 0, 2, 4 and 8 during the treatment period&#xD;
      and at week 10 at follow-up. Exclusion criteria will include a colectomy, positive stool&#xD;
      culture for common bacterial pathogens, a history of drug or alcohol abuse, mental illness,&#xD;
      concomitant immunological, hematologic or neoplastic disease, hepatic insufficiency, cardiac&#xD;
      insufficiency, pregnancy, treatment with anti-tumor necrosis factor agents within 3 months,&#xD;
      local steroids in the preceding 30 days, and antibiotics less than 15 days before screening.&#xD;
      Participants may continue concomitant medications at stable dosages for at least 12 weeks&#xD;
      before screening (medications include mesalamine, thiopurines, methotrexate, and probiotics).&#xD;
      Participants will continue current medication if she/he is stable with it; no washout period&#xD;
      is required. FLC will be a supplement therapy; dosages of concomitant medications must be&#xD;
      maintained constant throughout the study.&#xD;
&#xD;
      The introduction of biologics, steroids, or antibiotics or any dose increase of existing&#xD;
      medication during the study will be considered a treatment failure. Subjects meeting&#xD;
      inclusion and exclusion criteria will be randomized by a computer-generated algorithm in a&#xD;
      1:1 fashion to one of two treatment arms. Treatment Arm 1 will consist of 300 mg FLC taken&#xD;
      orally twice daily. The 600 mg dose of FLC is based on clinical research that suggests a&#xD;
      minimum dose of 500 mg/day dose of FLC is tolerable and necessary to observe significant&#xD;
      health benefits (i.e. reduction of cardiovascular risk). The placebo will consist of&#xD;
      unflavored whey protein (manufactured by Natural Factors®). FLC and placebo packets will be&#xD;
      prepared by study personnel in the College of Pharmacy and Nutrition under the supervision of&#xD;
      a licensed pharmacist. Participants and investigators will be blinded to treatment&#xD;
      allocation.&#xD;
&#xD;
      The primary outcome of interest will be the comparative proportion of subjects who complete&#xD;
      the study at week 8. Secondary endpoints will include the proportion of week 8 clinical&#xD;
      responders (as defined by a Mayo Score reduction of ≥ 3 points) and the proportion of&#xD;
      subjects with a post-therapy fecal calprotectin (Cp) concentration ≤ 150 μg/g at week 8.&#xD;
&#xD;
      The study will be powered to detect the primary endpoint, which is the proportion of subjects&#xD;
      completing the study at week 8 in the FLC versus the placebo-treated group. Power&#xD;
      calculations based upon a two-sided 95% confidence interval (α = 0.05) with an estimated&#xD;
      study completion rate of 0.40 in the placebo-treated group and 0.80 in the FLC treated group&#xD;
      indicate that 28 subjects will need to be recruited per group in order to detect a difference&#xD;
      (β = 0.80). Relevant covariates including smoking status, gender, age, disease duration and&#xD;
      disease severity will be compared between intervention and placebo groups using the χ2 test&#xD;
      of independence for categorical variables and ANOVA for continuous variables. Missing data&#xD;
      will be handled through multiple imputation techniques with appropriate sensitivity analysis&#xD;
      to investigate the effects of different imputation methods.&#xD;
&#xD;
      The use of the FLC complex holds promise in attenuating inflammation found in IBD. The&#xD;
      investigators suspect that using FLC in patients with mild to moderately severe UC will be&#xD;
      well-tolerated and efficacious. Data derived from this pilot study will inform planned future&#xD;
      national, double-blind, placebo-controlled intervention trials on the therapeutic potential&#xD;
      of flaxseed derived products in IBD and will be the first study of its kind to investigate&#xD;
      FLC as therapy in IBD.&#xD;
&#xD;
      The data derived from this pilot study will help to determine whether flaxseed derived&#xD;
      bioactive is a safe and cost-effective alternative therapeutic option for the treatment of&#xD;
      patients with IBD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 2018</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</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>
    <intervention_model_description>Flaxseed Lignan-Enriched Complex (FLC) vs. placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete study period</measure>
    <time_frame>8 weeks</time_frame>
    <description>The primary outcome of interest will be the comparative proportion of subjects who complete the study at week 8.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of clinical responders</measure>
    <time_frame>8 weeks</time_frame>
    <description>Proportion of week 8 clinical responders is defined by a Mayo Score reduction of ≥ 3 points</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Post-therapy fecal calprotectin (Cp)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Proportion of subjects with a post-therapy fecal calprotectin (Cp) concentration equal or less than 150 mg/g at week 8</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will consist of unflavored whey protein (manufactured by Natural Factors®)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>flaxseed lignan-enriched complex (FLC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will undergo treatment with FLC for an 8-week period; participants will take 300 mg flaxseed lignan-enriched complex (FLC) taken orally twice daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Flaxseed lignan-enriched complex (FLC)</intervention_name>
    <description>Subjects will undergo treatment with FLC for an 8-week period; participants will take 300 mg flaxseed lignan-enriched complex (FLC) taken orally twice daily</description>
    <arm_group_label>flaxseed lignan-enriched complex (FLC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will consist of unflavored whey protein (manufactured by Natural Factors®)</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Comparator: Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female or male aged 18 years and above&#xD;
&#xD;
          2. Patients diagnosed with mild to moderately severe, left-sided or pan-colonic UC (Mayo&#xD;
             Score 3 - 10 points)&#xD;
&#xD;
          3. Baseline vitamin D status and clinically indicated laboratory investigations such as&#xD;
             CBC, liver enzymes and serologic inflammatory marker high sensitivity c-reactive&#xD;
             protein (hsCRP).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients with the following conditions will be excluded:&#xD;
&#xD;
          -  colectomy&#xD;
&#xD;
          -  positive stool culture for common bacterial pathogens&#xD;
&#xD;
          -  history of drug or alcohol abuse&#xD;
&#xD;
          -  mental illness&#xD;
&#xD;
          -  concomitant immunological&#xD;
&#xD;
          -  hematologic or neoplastic disease&#xD;
&#xD;
          -  hepatic insufficiency&#xD;
&#xD;
          -  cardiac insufficiency&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  treatment with anti-tumor necrosis factor agents within 3 months&#xD;
&#xD;
          -  local steroids in the preceding 30 days and antibiotics less than 15 days before&#xD;
             screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Sharyle Fowler, MD,FRCPS</last_name>
    <phone>306-844-1125</phone>
    <email>sharyle.fowler@usask.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Royal University Hospital</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <zip>S7N 0W8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <contact>
      <last_name>Sharyle Fowler, MD</last_name>
      <phone>306-844-1125</phone>
      <email>sharyle.fowler@usask.ca</email>
    </contact>
    <investigator>
      <last_name>Jennifer Jones, MD, Msc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sharyle Fowler, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jane Alcorn, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gordon Zello, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Martin Reaney, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Juan-Nicolas Pena-Sanchez, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>June 11, 2018</last_update_submitted>
  <last_update_submitted_qc>June 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Saskatchewan</investigator_affiliation>
    <investigator_full_name>Sharyle Fowler</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <keyword>Inflammatory Bowel Disease (IBD), ulcerative colitis (UC), flaxseed lignan-enriched complex (FLC)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_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/NCT02201758
org study id: Bio 14-128
nct id: NCT02201758
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study proposes to examine the effect of diet as a modifiable risk factor among patients
      with ulcerative colitis (UC). Flax seeds contain many bioactive constituents which have
      anti-oxidative, anti-inflammatory, and anti-carcinogenic effects. These bioactive compounds
      represent novel classes of pharmacologically active compounds which may represent new options
      to treat chronic disease of the gastrointestinal tract. Participants with mild to moderately
      severe UC will supplement their current medications with flaxseed lignan-enriched complex
      (FLC). This is a 12 week double blind placebo controlled study with assessment throughout.
      Stool and blood samples (biomarkers) as well as bowel assessment via sigmoidoscopy will be
      evaluated before and after the intervention. The treatment arm consists of 300 mg FLC taken
      orally twice daily.
This project is a single centre, randomized, placebo-controlled pilot study in which subjects
      recruited to the study will undergo treatment with FLC for an 8-week period. The
      investigators will recruit patients with mild to moderately severe, left-sided or pan-colonic
      UC (Mayo Score 3 - 10 points). All participants will have vitamin D status evaluated at
      baseline and clinically indicated laboratory investigations including complete blood count
      (CBC), liver enzymes and serologic inflammatory marker high sensitivity c-reactive protein
      (hsCRP). Participants will be evaluated at weeks 0, 2, 4 and 8 during the treatment period
      and at week 10 at follow-up. Exclusion criteria will include a colectomy, positive stool
      culture for common bacterial pathogens, a history of drug or alcohol abuse, mental illness,
      concomitant immunological, hematologic or neoplastic disease, hepatic insufficiency, cardiac
      insufficiency, pregnancy, treatment with anti-tumor necrosis factor agents within 3 months,
      local steroids in the preceding 30 days, and antibiotics less than 15 days before screening.
      Participants may continue concomitant medications at stable dosages for at least 12 weeks
      before screening (medications include mesalamine, thiopurines, methotrexate, and probiotics).
      Participants will continue current medication if she/he is stable with it; no washout period
      is required. FLC will be a supplement therapy; dosages of concomitant medications must be
      maintained constant throughout the study.

      The introduction of biologics, steroids, or antibiotics or any dose increase of existing
      medication during the study will be considered a treatment failure. Subjects meeting
      inclusion and exclusion criteria will be randomized by a computer-generated algorithm in a
      1:1 fashion to one of two treatment arms. Treatment Arm 1 will consist of 300 mg FLC taken
      orally twice daily. The 600 mg dose of FLC is based on clinical research that suggests a
      minimum dose of 500 mg/day dose of FLC is tolerable and necessary to observe significant
      health benefits (i.e. reduction of cardiovascular risk). The placebo will consist of
      unflavored whey protein (manufactured by Natural Factors®). FLC and placebo packets will be
      prepared by study personnel in the College of Pharmacy and Nutrition under the supervision of
      a licensed pharmacist. Participants and investigators will be blinded to treatment
      allocation.

      The primary outcome of interest will be the comparative proportion of subjects who complete
      the study at week 8. Secondary endpoints will include the proportion of week 8 clinical
      responders (as defined by a Mayo Score reduction of ≥ 3 points) and the proportion of
      subjects with a post-therapy fecal calprotectin (Cp) concentration ≤ 150 μg/g at week 8.

      The study will be powered to detect the primary endpoint, which is the proportion of subjects
      completing the study at week 8 in the FLC versus the placebo-treated group. Power
      calculations based upon a two-sided 95% confidence interval (α = 0.05) with an estimated
      study completion rate of 0.40 in the placebo-treated group and 0.80 in the FLC treated group
      indicate that 28 subjects will need to be recruited per group in order to detect a difference
      (β = 0.80). Relevant covariates including smoking status, gender, age, disease duration and
      disease severity will be compared between intervention and placebo groups using the χ2 test
      of independence for categorical variables and ANOVA for continuous variables. Missing data
      will be handled through multiple imputation techniques with appropriate sensitivity analysis
      to investigate the effects of different imputation methods.

      The use of the FLC complex holds promise in attenuating inflammation found in IBD. The
      investigators suspect that using FLC in patients with mild to moderately severe UC will be
      well-tolerated and efficacious. Data derived from this pilot study will inform planned future
      national, double-blind, placebo-controlled intervention trials on the therapeutic potential
      of flaxseed derived products in IBD and will be the first study of its kind to investigate
      FLC as therapy in IBD.

      The data derived from this pilot study will help to determine whether flaxseed derived
      bioactive is a safe and cost-effective alternative therapeutic option for the treatment of
      patients with IBD.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Flaxseed Lignan-Enriched Complex (FLC) vs. placebo
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Complete study period
time frame: 8 weeks
description: The primary outcome of interest will be the comparative proportion of subjects who complete the study at week 8.
measure: Proportion of clinical responders
time frame: 8 weeks
description: Proportion of week 8 clinical responders is defined by a Mayo Score reduction of ≥ 3 points
measure: Post-therapy fecal calprotectin (Cp)
time frame: 8 weeks
description: Proportion of subjects with a post-therapy fecal calprotectin (Cp) concentration equal or less than 150 mg/g at week 8
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will consist of unflavored whey protein (manufactured by Natural Factors®)
arm group label: flaxseed lignan-enriched complex (FLC)
arm group type: Experimental
description: Subjects will undergo treatment with FLC for an 8-week period; participants will take 300 mg flaxseed lignan-enriched complex (FLC) taken orally twice daily
intervention type: Dietary Supplement
intervention name: Flaxseed lignan-enriched complex (FLC)
description: Subjects will undergo treatment with FLC for an 8-week period; participants will take 300 mg flaxseed lignan-enriched complex (FLC) taken orally twice daily
arm group label: flaxseed lignan-enriched complex (FLC)
intervention type: Other
intervention name: Placebo
description: Placebo will consist of unflavored whey protein (manufactured by Natural Factors®)
arm group label: Placebo
other name: Placebo Comparator: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sharyle Fowler, MD,FRCPS
phone: 306-844-1125
email: sharyle.fowler@usask.ca
facility: 
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Saskatchewan
investigator full name: Sharyle Fowler
investigator title: M.D.
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer