<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/NCT02195960</url>
  </required_header>
  <id_info>
    <org_study_id>Neuromed-ATH-EU2014</org_study_id>
    <nct_id>NCT02195960</nct_id>
  </id_info>
  <brief_title>Supplementation With Dietary Anthocyanins and Side Effects of Radiotherapy for Breast Cancer</brief_title>
  <acronym>ATHENA</acronym>
  <official_title>Supplementation With Dietary Anthocyanins and Side Effects of Radiotherapy for Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neuromed IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neuromed IRCCS</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Attention has been focused recently on the development of modalities that can protect healthy&#xD;
      organs from the harmful effects of radiation applied during different cancer treatment&#xD;
      schedules. As radiation-induced DNA damage involves oxidative stress, the protective role of&#xD;
      antioxidants has been tested in different dietary studies. Previous experience by the&#xD;
      collaborative team of the principal investigator and radiotherapists at the Catholic&#xD;
      University of Campobasso has shown in a retrospective study that moderate wine consumption&#xD;
      can reduce the side-effects of radiation therapy in patients with breast cancer. This effect&#xD;
      was presumably due to the polyphenol non alcoholic fraction of wine, a finding in agreement&#xD;
      with a cross-over intervention study in adult male volunteers, on protection by&#xD;
      de-alcoholized red wine from ex vivo radiation-induced DNA damage.&#xD;
&#xD;
      The purpose of this clinical trial will be to test the impact of supplementation with&#xD;
      anthocyanin-enriched food on the acute and medium-term side effects of radiotherapy in breast&#xD;
      cancer patients, in a prospective study design. Therefore a double blind, randomised,&#xD;
      placebo-controlled clinical trial will be organised by assigning patients with breast cancer&#xD;
      scheduled for radiotherapy to a diet supplemented with an anthocyanin soluble extract.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Detailed Description&#xD;
&#xD;
        1. Study Rationale:&#xD;
&#xD;
           Attention has been focused recently on the development of modalities that can protect&#xD;
           healthy organs from the harmful effects of radiation applied during different cancer&#xD;
           treatment schedules. As radiation-induced DNA and cellular damage involve oxidative&#xD;
           stress, the protective role of antioxidants will be tested on the toxic condition&#xD;
           induced by radiotherapy in breast cancer treatment. Consumption of polyphenol-rich&#xD;
           foods, such as fruits and vegetables, and beverages derived from plants, such as cocoa,&#xD;
           red wine and tea, may represent a beneficial diet in terms of oxidative protection.&#xD;
           Indeed, a retrospective study reports that that moderate wine consumption can reduce the&#xD;
           side-effects of radiation therapy in patients with breast cancer. This effect was&#xD;
           presumably due to the polyphenol non alcoholic fraction of wine, a finding in agreement&#xD;
           with a cross-over intervention study in adult male volunteers, on protection by&#xD;
           de-alcoholized red wine from ex vivo radiation-induced DNA damage. However, there are no&#xD;
           studies that address the relationship of polyphenol-rich food consumption with the toxic&#xD;
           effects of radiations in patients undergoing radiotherapy for breast cancer treatment.&#xD;
&#xD;
        2. Aim of the study. The main objectives of this study are to evaluate the association&#xD;
           between the effect of polyphenol-rich food supplementation and toxicity of radiotherapy&#xD;
           for breast cancer.&#xD;
&#xD;
        3. Study design: Randomized, placebo-controlled double-blind trial with 2 parallel arms:&#xD;
           soluble corn flour at high content in anthocyanins and placebo. Placebo consists of&#xD;
           soluble corn flour poor in anthocyanins. The treatment will start one week before&#xD;
           starting radiotherapy, and continue during all radiotherapy treatment (of 3 or 5 weeks).&#xD;
&#xD;
        4. Study Population and recruitment: A total of 300 consecutive breast cancer patients&#xD;
           eligible for radiotherapy. Participants will be identified at the Department of&#xD;
           Radiotherapy of the Giovanni Paolo II Foundation of Campobasso.&#xD;
&#xD;
      Eligible subjects will be recruited at their first consultation and subsequently referred to&#xD;
      the research investigators. The research staff in charge of the recruitment will pre-screen&#xD;
      participants on the basis of inclusion/exclusion criteria and will explain the study at this&#xD;
      time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2014</start_date>
  <completion_date type="Actual">October 10, 2018</completion_date>
  <primary_completion_date type="Actual">June 26, 2017</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Corn cobs-derived extracts of soluble anthocyanins given to breast cancer patients undergoing radiotherapy, to test prevention of skin toxicity.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Patients, doctors, RT technicians, investigators and statisticians who participated or evaluated the study outcomes were blinded to the nature of the supplements. Anthocyanin and placebo stick packs and soluble granulated products were identical for organoleptic properties and coded as A and B by the producer. Only after completion of statistical analyses of trial results, blind codes were opened by the provider.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>side effects of radiotherapy</measure>
    <time_frame>4 or 6 weeks, according to the radiotherapy protocol</time_frame>
    <description>Prevention of side effects - skin toxicity - of radiotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute skin toxicity</measure>
    <time_frame>1 month after the end of treatment (8 or 10 weeks)</time_frame>
    <description>Secondary end-points are late toxicity, cosmetic results, local control, and survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral markers of inflammation</measure>
    <time_frame>before starting treatment, at the end (4 or 6 weeks) and 1 month after radiotherapy (8 or 10 weeks)</time_frame>
    <description>Blood cells count, markers of plasma and cell oxidation, markers of inflammatory response and oxidative DNA damage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral markers of bioavailability</measure>
    <time_frame>before starting and at the end of treatment (4 or 6 weeks)</time_frame>
    <description>Anthocyanins excretion will be evaluated in urine samples by analytical techniques.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>long-term skin toxicity</measure>
    <time_frame>6 and 12 months after the end of radiotherapy, corresponding to 7 or 7.5 months and 13 or 13.5 months from the beginning of the study</time_frame>
    <description>late toxicity, cosmetic results, local control, and survival</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">242</enrollment>
  <condition>Toxicity Due to Radiotherapy</condition>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>intake corn extract poor in anthocyanins: three daily stick packs containing water-soluble extract from corn cobs poor in anthocyanins</description>
  </arm_group>
  <arm_group>
    <arm_group_label>intake anthocyanin-rich corn extract</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>intake anthocyanin-rich corn extract: three daily stick packs containing water-soluble extract from high-anthocyanin rich corn cobs</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>intake corn extract poor in anthocyanins: three daily stick packs containing water-soluble extract from corn cobs poor in anthocyanins</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>intake anthocyanin-rich corn extract</intervention_name>
    <description>intake anthocyanin-rich corn extract: three daily stick packs containing water-soluble extract from high-anthocyanin rich corn cobs</description>
    <arm_group_label>intake anthocyanin-rich corn extract</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient must consent to be in the study and must have signed an approved consent&#xD;
             form conforming with institutional guidelines.&#xD;
&#xD;
          2. Patients must be ≥ 18 years old.&#xD;
&#xD;
          3. On histological examination, the tumor must be DCIS or invasive carcinoma of the&#xD;
             breast.&#xD;
&#xD;
          4. Surgical treatment of the breast must have been lumpectomy or quadrantectomy. The&#xD;
             margins of the resected specimen must be histologically free of tumor (DCIS and&#xD;
             invasive). Reexcision of surgical margins is permitted.&#xD;
&#xD;
          5. Patients with invasive breast cancer are required to have axillary staging which can&#xD;
             include sentinel node biopsy alone (if sentinel node is negative), sentinel node&#xD;
             biopsy followed by axillary dissection or sampling with a minimum total of 6 axillary&#xD;
             nodes (if sentinel node is positive), or axillary dissection alone (with a minimum of&#xD;
             6 axillary nodes). (Axillary staging is not required for patients with DCIS.)&#xD;
&#xD;
          6. The patient must be randomized within 45 days following the last surgery for breast&#xD;
             cancer (lumpectomy, re-excision of margins, or axillary staging procedure) or within&#xD;
             30 days following the last chemotherapy cycle.&#xD;
&#xD;
          7. Patients with a history of non-breast malignancies are eligible if they have been&#xD;
             disease-free for 5 or more years prior to randomization and are deemed by their&#xD;
             physician to be at low risk for recurrence. Patients with the following cancers are&#xD;
             eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the&#xD;
             cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous&#xD;
             cell carcinoma of the skin.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Axillary nodes with definite evidence of microscopic or macroscopic extracapsular&#xD;
             extension.&#xD;
&#xD;
          2. One or more positive non-axillary sentinel node(s). (Note that intramammary nodes are&#xD;
             staged as axillary nodes.)&#xD;
&#xD;
          3. Palpable or radiographically suspicious ipsilateral or contralateral axillary,&#xD;
             supraclavicular, infraclavicular, or internal mammary nodes, unless there is&#xD;
             histologic confirmation that these nodes are negative for tumor.&#xD;
&#xD;
          4. Suspicious microcalcifications, densities, or palpable abnormalities (in the&#xD;
             ipsilateral or contralateral breast) unless biopsied and found to be benign.&#xD;
&#xD;
          5. Non-epithelial breast malignancies such as sarcoma or lymphoma.&#xD;
&#xD;
          6. Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or&#xD;
             separated by 4 or more centimeters.&#xD;
&#xD;
          7. Paget's disease of the nipple.&#xD;
&#xD;
          8. Synchronous bilateral invasive or non-invasive breast cancer.&#xD;
&#xD;
          9. Surgical margins that cannot be microscopically assessed or are positive at pathologic&#xD;
             evaluation. (If surgical margins are rendered free of disease by reexcision, the&#xD;
             patient is eligible.)&#xD;
&#xD;
         10. Breast implants. (Patients who have had implants removed are eligible.)&#xD;
&#xD;
         11. Prior breast or thoracic radiation therapy for any condition.&#xD;
&#xD;
         12. Collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase&#xD;
             level above normal or with an active skin rash, systemic lupus erythematosus, or&#xD;
             scleroderma.&#xD;
&#xD;
         13. Pregnancy or lactation at the time of proposed randomization. Women of reproductive&#xD;
             potential must agree to use an effective non-hormonal method of contraception during&#xD;
             therapy.&#xD;
&#xD;
         14. Psychiatric or addictive disorders or other conditions that, in the opinion of the&#xD;
             investigator, would preclude the patient from meeting the study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria Benedetta Donati, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Neuromed IRCCS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Radiotherapy</name>
      <address>
        <city>Campobasso</city>
        <state>CB</state>
        <zip>86100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>June 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>January 26, 2021</last_update_submitted>
  <last_update_submitted_qc>January 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Neuromed IRCCS</investigator_affiliation>
    <investigator_full_name>Maria Benedetta Donati</investigator_full_name>
    <investigator_title>head laboratory</investigator_title>
  </responsible_party>
  <keyword>skin toxicity, radiotherapy, antioxidants</keyword>
  <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/NCT02195960
org study id: Neuromed-ATH-EU2014
nct id: NCT02195960
lead sponsor: 
has dmc: No
Attention has been focused recently on the development of modalities that can protect healthy
      organs from the harmful effects of radiation applied during different cancer treatment
      schedules. As radiation-induced DNA damage involves oxidative stress, the protective role of
      antioxidants has been tested in different dietary studies. Previous experience by the
      collaborative team of the principal investigator and radiotherapists at the Catholic
      University of Campobasso has shown in a retrospective study that moderate wine consumption
      can reduce the side-effects of radiation therapy in patients with breast cancer. This effect
      was presumably due to the polyphenol non alcoholic fraction of wine, a finding in agreement
      with a cross-over intervention study in adult male volunteers, on protection by
      de-alcoholized red wine from ex vivo radiation-induced DNA damage.

      The purpose of this clinical trial will be to test the impact of supplementation with
      anthocyanin-enriched food on the acute and medium-term side effects of radiotherapy in breast
      cancer patients, in a prospective study design. Therefore a double blind, randomised,
      placebo-controlled clinical trial will be organised by assigning patients with breast cancer
      scheduled for radiotherapy to a diet supplemented with an anthocyanin soluble extract.
Detailed Description

        1. Study Rationale:

           Attention has been focused recently on the development of modalities that can protect
           healthy organs from the harmful effects of radiation applied during different cancer
           treatment schedules. As radiation-induced DNA and cellular damage involve oxidative
           stress, the protective role of antioxidants will be tested on the toxic condition
           induced by radiotherapy in breast cancer treatment. Consumption of polyphenol-rich
           foods, such as fruits and vegetables, and beverages derived from plants, such as cocoa,
           red wine and tea, may represent a beneficial diet in terms of oxidative protection.
           Indeed, a retrospective study reports that that moderate wine consumption can reduce the
           side-effects of radiation therapy in patients with breast cancer. This effect was
           presumably due to the polyphenol non alcoholic fraction of wine, a finding in agreement
           with a cross-over intervention study in adult male volunteers, on protection by
           de-alcoholized red wine from ex vivo radiation-induced DNA damage. However, there are no
           studies that address the relationship of polyphenol-rich food consumption with the toxic
           effects of radiations in patients undergoing radiotherapy for breast cancer treatment.

        2. Aim of the study. The main objectives of this study are to evaluate the association
           between the effect of polyphenol-rich food supplementation and toxicity of radiotherapy
           for breast cancer.

        3. Study design: Randomized, placebo-controlled double-blind trial with 2 parallel arms:
           soluble corn flour at high content in anthocyanins and placebo. Placebo consists of
           soluble corn flour poor in anthocyanins. The treatment will start one week before
           starting radiotherapy, and continue during all radiotherapy treatment (of 3 or 5 weeks).

        4. Study Population and recruitment: A total of 300 consecutive breast cancer patients
           eligible for radiotherapy. Participants will be identified at the Department of
           Radiotherapy of the Giovanni Paolo II Foundation of Campobasso.

      Eligible subjects will be recruited at their first consultation and subsequently referred to
      the research investigators. The research staff in charge of the recruitment will pre-screen
      participants on the basis of inclusion/exclusion criteria and will explain the study at this
      time.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Corn cobs-derived extracts of soluble anthocyanins given to breast cancer patients undergoing radiotherapy, to test prevention of skin toxicity.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Patients, doctors, RT technicians, investigators and statisticians who participated or evaluated the study outcomes were blinded to the nature of the supplements. Anthocyanin and placebo stick packs and soluble granulated products were identical for organoleptic properties and coded as A and B by the producer. Only after completion of statistical analyses of trial results, blind codes were opened by the provider.
measure: side effects of radiotherapy
time frame: 4 or 6 weeks, according to the radiotherapy protocol
description: Prevention of side effects - skin toxicity - of radiotherapy
measure: Acute skin toxicity
time frame: 1 month after the end of treatment (8 or 10 weeks)
description: Secondary end-points are late toxicity, cosmetic results, local control, and survival.
measure: Peripheral markers of inflammation
time frame: before starting treatment, at the end (4 or 6 weeks) and 1 month after radiotherapy (8 or 10 weeks)
description: Blood cells count, markers of plasma and cell oxidation, markers of inflammatory response and oxidative DNA damage
measure: Peripheral markers of bioavailability
time frame: before starting and at the end of treatment (4 or 6 weeks)
description: Anthocyanins excretion will be evaluated in urine samples by analytical techniques.
measure: long-term skin toxicity
time frame: 6 and 12 months after the end of radiotherapy, corresponding to 7 or 7.5 months and 13 or 13.5 months from the beginning of the study
description: late toxicity, cosmetic results, local control, and survival
arm group label: placebo
arm group type: Placebo Comparator
description: intake corn extract poor in anthocyanins: three daily stick packs containing water-soluble extract from corn cobs poor in anthocyanins
arm group label: intake anthocyanin-rich corn extract
arm group type: Active Comparator
description: intake anthocyanin-rich corn extract: three daily stick packs containing water-soluble extract from high-anthocyanin rich corn cobs
intervention type: Dietary Supplement
intervention name: Placebo
description: intake corn extract poor in anthocyanins: three daily stick packs containing water-soluble extract from corn cobs poor in anthocyanins
arm group label: placebo
intervention type: Dietary Supplement
intervention name: intake anthocyanin-rich corn extract
description: intake anthocyanin-rich corn extract: three daily stick packs containing water-soluble extract from high-anthocyanin rich corn cobs
arm group label: intake anthocyanin-rich corn extract
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria Benedetta Donati, MD PhD
role: Principal Investigator
affiliation: Neuromed IRCCS
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Neuromed IRCCS
investigator full name: Maria Benedetta Donati
investigator title: head laboratory
sharing ipd: No