<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/NCT01715480</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00033630</org_study_id>
    <nct_id>NCT01715480</nct_id>
  </id_info>
  <brief_title>Effect of Broccoli Sprouts Homogenate on SS RBC</brief_title>
  <acronym>BSH</acronym>
  <official_title>Physiological Effect of Sulforaphane Obtained From Broccoli Sprouts Homogenates (BSH) on the HbF and Anti-oxidative Capacity of Human Sickle Red Blood Cells (SS RBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Doris Duke Charitable Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall purpose of this study is to obtain a better understanding of the biological&#xD;
      response of red blood cells to sulforaphane contained in fresh broccoli sprouts that have&#xD;
      been put through a blending process. This study will use commercially available fresh&#xD;
      broccoli sprouts certified by Brassica Protection Products LLC (BroccoSprouts®). This product&#xD;
      can also be purchased at some local grocery stores in the produce section. It is believed&#xD;
      that NRF2, a transcription factor encoded by the NFE2L2 gene, plays a role in the regulation&#xD;
      of defense against oxidative stress. The detrimental accelerated breakdown of sickle cell&#xD;
      disease (SCD) red blood cells (SS RBC) is partially due to reduced anti-oxidative capacity.&#xD;
      Previous analysis of SS RBC microRNAs revealed that a reduced level of NRF2, the master&#xD;
      regulator of anti-oxidative stress capacity, contributes to reduced resistance to oxidative&#xD;
      stress and increased hemolysis; NRF2 also induces fetal hemoglobin (HbF), which is known to&#xD;
      prevent SS RBC sickling.&#xD;
&#xD;
      First, erythroid progenitors from normal and SCD subjects will be tested ex-vivo to find out&#xD;
      how sulforaphane, a natural NRF2 activator, affects the oxidative stress capacity, HbF&#xD;
      expression, and microRNA expression of red cells.&#xD;
&#xD;
      Second, a pilot clinical trial will be conducted to determine the safety and physiological&#xD;
      effects of 3 weeks of daily consumption of broccoli sprout homogenate in a cohort of Hb&#xD;
      SS/SB0 thalassemia adult SCD patients. During this study, subjects RBCs will be assayed for&#xD;
      changes in anti-oxidative stress capacity and microRNA composition in mature SCD red blood&#xD;
      cells.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2012</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>In vitro response of HbAA and HbSS erythroid cells to NRF2 activation by sulforaphane.</measure>
    <time_frame>3 months</time_frame>
    <description>Erythroid progenitor cells from 3 volunteers with Hb AA and 3 subjects with Hb SS disease will be exposed to sulforaphane and then their expression levels of genes regulated by Nrf2 will be measured.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety, physiological effects and cellular effects of daily consumption of broccoli sprout homogenate in a cohort of Hb SS/SB0 thalassemia adult SCD patients</measure>
    <time_frame>1-2 years</time_frame>
    <description>Adult subjects with Hb SS/SB0 thalassemia will be recruited to participate in this part of the study. Subjects will be asked to consume broccoli sprout that have been blended into a milkshake-like substance daily for three consecutive weeks. Safety measures will include recording of vital signs and adverse signs and symptoms. Assessment of physiological effects will include measurement of blood chemistries, counts, LDH, and hemoglobin F level. Measurements of cellular effects will include changes in microRNA gene profiling, gene expression profiling, and quantitation of anti-oxidant capacity.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Sickle Red Blood Cell</condition>
  <condition>Fetal Hemoglobin</condition>
  <condition>Oxidative Stress</condition>
  <arm_group>
    <arm_group_label>Broccoli sprout homogenate ingestion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will ingest broccoli sprout homogenate in the form of a shake.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Broccosprouts® (Brassica Protection Products LLC) homogenate</intervention_name>
    <description>In the in-vitro part of the study, sulphoraphane will be added into the culture media used to grow and differentiate the erythroid cells from blood samples obtained from three Hb AA volunteers and three Hb SS subjects. The subjects will have a single clinic visit for the blood donation.&#xD;
In the second part of the study, enrolled subjects will be asked to consume homogenates of broccoli sprouts by mouth daily for three weeks. They will have a maximum of five clinic visits for medical assessments and lab draws during this time. They will then have a final clinic visit after a washout period of six weeks.</description>
    <arm_group_label>Broccoli sprout homogenate ingestion</arm_group_label>
    <other_name>Broccoli sprout</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Hemoglobin (Hb) SS or Hb Sβ0 thalassemia by electrophoresis&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Hematocrit (Hct) ≥ 20% and Hb &gt; 6.0 g/dL&#xD;
&#xD;
          -  Capacity to understand and sign informed consent and can adhere to the daily regimen&#xD;
             of BSH&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  RBC transfusion or change in hydroxyurea dose during the 3 months prior to study entry&#xD;
&#xD;
          -  Ongoing pregnancy&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Renal insufficiency (BUN &gt;21 mg/dL and/or Creatinine &gt;1.4 mg/dL)&#xD;
&#xD;
          -  History of allergy to sulfonamides&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jen-Tsan A Chi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marilyn J Telen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Sangokoya C, Telen MJ, Chi JT. microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease. Blood. 2010 Nov 18;116(20):4338-48. doi: 10.1182/blood-2009-04-214817. Epub 2010 Aug 13.</citation>
    <PMID>20709907</PMID>
  </reference>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>March 6, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>May 27, 2015</last_update_submitted>
  <last_update_submitted_qc>May 27, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 28, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>broccoli sprout</keyword>
  <keyword>sickle cell</keyword>
  <keyword>NRF2</keyword>
  <!-- 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/NCT01715480
org study id: Pro00033630
nct id: NCT01715480
lead sponsor: 
collaborator: 
has dmc: Yes
The overall purpose of this study is to obtain a better understanding of the biological
      response of red blood cells to sulforaphane contained in fresh broccoli sprouts that have
      been put through a blending process. This study will use commercially available fresh
      broccoli sprouts certified by Brassica Protection Products LLC (BroccoSprouts®). This product
      can also be purchased at some local grocery stores in the produce section. It is believed
      that NRF2, a transcription factor encoded by the NFE2L2 gene, plays a role in the regulation
      of defense against oxidative stress. The detrimental accelerated breakdown of sickle cell
      disease (SCD) red blood cells (SS RBC) is partially due to reduced anti-oxidative capacity.
      Previous analysis of SS RBC microRNAs revealed that a reduced level of NRF2, the master
      regulator of anti-oxidative stress capacity, contributes to reduced resistance to oxidative
      stress and increased hemolysis; NRF2 also induces fetal hemoglobin (HbF), which is known to
      prevent SS RBC sickling.

      First, erythroid progenitors from normal and SCD subjects will be tested ex-vivo to find out
      how sulforaphane, a natural NRF2 activator, affects the oxidative stress capacity, HbF
      expression, and microRNA expression of red cells.

      Second, a pilot clinical trial will be conducted to determine the safety and physiological
      effects of 3 weeks of daily consumption of broccoli sprout homogenate in a cohort of Hb
      SS/SB0 thalassemia adult SCD patients. During this study, subjects RBCs will be assayed for
      changes in anti-oxidative stress capacity and microRNA composition in mature SCD red blood
      cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: In vitro response of HbAA and HbSS erythroid cells to NRF2 activation by sulforaphane.
time frame: 3 months
description: Erythroid progenitor cells from 3 volunteers with Hb AA and 3 subjects with Hb SS disease will be exposed to sulforaphane and then their expression levels of genes regulated by Nrf2 will be measured.
measure: Safety, physiological effects and cellular effects of daily consumption of broccoli sprout homogenate in a cohort of Hb SS/SB0 thalassemia adult SCD patients
time frame: 1-2 years
description: Adult subjects with Hb SS/SB0 thalassemia will be recruited to participate in this part of the study. Subjects will be asked to consume broccoli sprout that have been blended into a milkshake-like substance daily for three consecutive weeks. Safety measures will include recording of vital signs and adverse signs and symptoms. Assessment of physiological effects will include measurement of blood chemistries, counts, LDH, and hemoglobin F level. Measurements of cellular effects will include changes in microRNA gene profiling, gene expression profiling, and quantitation of anti-oxidant capacity.
arm group label: Broccoli sprout homogenate ingestion
arm group type: Experimental
description: Subjects will ingest broccoli sprout homogenate in the form of a shake.
intervention type: Dietary Supplement
intervention name: Broccosprouts® (Brassica Protection Products LLC) homogenate
description: In the in-vitro part of the study, sulphoraphane will be added into the culture media used to grow and differentiate the erythroid cells from blood samples obtained from three Hb AA volunteers and three Hb SS subjects. The subjects will have a single clinic visit for the blood donation.
In the second part of the study, enrolled subjects will be asked to consume homogenates of broccoli sprouts by mouth daily for three weeks. They will have a maximum of five clinic visits for medical assessments and lab draws during this time. They will then have a final clinic visit after a washout period of six weeks.
arm group label: Broccoli sprout homogenate ingestion
other name: Broccoli sprout
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jen-Tsan A Chi, MD, PhD
role: Principal Investigator
affiliation: Duke University
last name: Marilyn J Telen, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
citation: Sangokoya C, Telen MJ, Chi JT. microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease. Blood. 2010 Nov 18;116(20):4338-48. doi: 10.1182/blood-2009-04-214817. Epub 2010 Aug 13.
PMID: 20709907
responsible party type: Sponsor