xml: <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/NCT05966441</url>
    </required_header>
    <id_info>
      <org_study_id>Paclitaxel induced PN</org_study_id>
      <nct_id>NCT05966441</nct_id>
    </id_info>
    <brief_title>Role of Curcumin in Paclitaxel Induced PN</brief_title>
    <official_title>Evaluating the Effect of Curcumin in Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ain Shams University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Ain Shams University</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Paclitaxel induced peripheral neuropathy is the most common and serious side effect&#xD;
        associated with Paclitaxel treatment in breast cancer patients receiving Paclitaxel.&#xD;
  &#xD;
        The efficacy of antioxidant molecules as neuroprotective strategies to preventing the&#xD;
        development of peripheral neuropathy has been investigated in preclinical and clinical&#xD;
        studies. Vitamin E and Glutathione have been explored as adjuvant therapies to preventing&#xD;
        taxane-induced peripheral neuropathy. Other tested neuroprotective treatments with limited&#xD;
        success include amifostine, glutamine and acetyl l-carnitine. Curcumin's antioxidant capacity&#xD;
        is similar to other potent antioxidants, such as trolox (a vitamin E analog). Curcumin&#xD;
        inhibits lipid peroxidation in different tissues, regulates intracellular levels of&#xD;
        antioxidant enzymes (e.g., catalase, glutathione peroxidase and superoxide dismutase) and is&#xD;
        an effective intracellular reactive oxygen species (ROS) scavenger.&#xD;
  &#xD;
        The investigators are going to investigate the neuroprotective effect of Curcumin against&#xD;
        Paclitaxel induced peripheral neuropathy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The work is a prospective, randomized, open label controlled study. A total of 90 breast&#xD;
        cancer female patients will be enrolled in the study. Eligible patients will simply be&#xD;
        randomized using random allocation generator, after the end of anthracycline adjuvant therapy&#xD;
        to one of two groups, Group I: will receive paclitaxel regimen plus 2g of curcumin Group II:&#xD;
        will receive paclitaxel regimen only.&#xD;
  &#xD;
        The cases involved in the study will be recruited from Ain Shams Teaching Hospital.&#xD;
  &#xD;
        All patients presenting to the department were assessed for eligibility according to certain&#xD;
        inclusion and exclusion criteria.&#xD;
  &#xD;
        Details of the research steps that the subscriber will be exposed to:&#xD;
  &#xD;
          -  Base line evaluation then alignment in either intervention or control group either for&#xD;
             taking the interventional drug or standard of care in control group.&#xD;
  &#xD;
          -  Blood samples will be collected at baseline.&#xD;
  &#xD;
          -  Patient will be given a weekly supply of the medication and will be asked to take his&#xD;
             prescribed dose daily.&#xD;
  &#xD;
          -  Every week all patients will be asked about their symptoms and if they experience any&#xD;
             adverse drug reaction.&#xD;
  &#xD;
          -  Patients will receive the interventional drug until the last paclitaxel dose will be&#xD;
             taken.&#xD;
  &#xD;
          -  After 3 months, another full clinical examination and blood sample will be obtained.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 30, 2023</start_date>
    <completion_date type="Anticipated">March 10, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 15, 2023</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>Details of the research steps that the subscriber will be exposed to:&#xD;
  Base line evaluation then alignment in either intervention or control group either for taking the interventional drug or standard of care in control group.&#xD;
  Blood samples will be collected at baseline.&#xD;
  Patient will be given a weekly supply of the medication and will be asked to take his prescribed dose daily.&#xD;
  Every week all patients will be asked about their symptoms and if they experience any adverse drug reaction.&#xD;
  Patients will receive the interventional drug until the last paclitaxel dose will be taken.&#xD;
  After 3 months, another full clinical examination and blood sample will be obtained.</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Evaluate the effect of Curcumin on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients.</measure>
      <time_frame>Baseline</time_frame>
      <description>After each cycle, initial evaluation of response will be done guided by clinical examination and functional assessment and questionnaire.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Evaluate the effect of Curcumin on the damage of nerve fibers induced by paclitaxel.</measure>
      <time_frame>Baseline</time_frame>
      <description>Nerve growth factor level will be obtained at day 0 and at the end of the paclitaxel course</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Evaluate the effect of adding curcumin to paclitaxel-based chemotherapy on response rate in neoadjuvant therapy.</measure>
      <time_frame>baseline</time_frame>
      <description>CT scan will be done before first dose of paclitaxel and at the end of the course</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Chemotherapy-induced Peripheral Neuropathy</condition>
    <arm_group>
      <arm_group_label>Experimental group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive their Paclitaxel-based chemotherapy along with Curcumin at a dose of oral 2g daily till the end of chemotherapy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Patients will receive their Paclitaxel-based chemotherapy only</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Curcumin</intervention_name>
      <description>The safety of curcumin has been widely demonstrated, and curcumin has a variety of potential pharmaceutical applications. Curcumin exhibits antioxidant, anti-inflammatory and anticancer properties and has been described as neuroprotective against neurological disorders.&#xD;
  Many of curcumin's pharmacological benefits arise from its antioxidant or anti-inflammatory properties. Curcumin appears to have significant potential for treatment of diseases that result from oxidative stress.&#xD;
  Curcumin is provided in soft gelatin capsules each capsule contains 1 g of curcumin and patient is asked to take 2 capsules daily</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Experimental group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Paclitaxel</intervention_name>
      <description>Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer Paclitaxel dose in adjuvant therapy after doxorubicin and cyclophosphamide every 3 weeks 175mg/m2 IV or Weekly 80 mg/m2 IV..&#xD;
  Paclitaxel dose in neoadjuvant therapy every 3 weeks 175 mg/m2 IV.</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Experimental group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Clinical diagnosis of early stage breast cancer with age &gt; 18 years.&#xD;
  &#xD;
            -  Performance status of the patients based on Eastern Cooperative Oncology Group (ECOG)&#xD;
               from 0 to 2.&#xD;
  &#xD;
            -  Patients must receive paclitaxel 80 mg/m2 weekly or 175 mg/m2 every 3 weeks for 12&#xD;
               weeks.&#xD;
  &#xD;
            -  Patients clinical parameters should be (ANC ≥ 1500/mm3). Platelet count 100,000/mm3)&#xD;
               (serum total bilirubin &lt; 1.5 mg/dl) and (creatinine &lt; 1.5 mg/dl).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients they had any signs and symptoms of clinical neuropathy.&#xD;
  &#xD;
            -  Diabetes mellitus&#xD;
  &#xD;
            -  Patients receiving vitamin supplementation including vitamin B1, B6 and B12&#xD;
  &#xD;
            -  Patients receiving antidepressants, anticoagulants, opioids or anticonvulsants&#xD;
  &#xD;
            -  Patients had a hypersensitivity to curcumin.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Sherif Gawish, master student</last_name>
      <phone>00201019700299</phone>
      <email>sherif.gawish2020@gmail.com</email>
    </overall_contact>
    <reference>
      <citation>Zhang X, Guan Z, Wang X, Sun D, Wang D, Li Y, Pei B, Ye M, Xu J, Yue X. Curcumin Alleviates Oxaliplatin-Induced Peripheral Neuropathic Pain through Inhibiting Oxidative Stress-Mediated Activation of NF-kappaB and Mitigating Inflammation. Biol Pharm Bull. 2020 Feb 1;43(2):348-355. doi: 10.1248/bpb.b19-00862. Epub 2019 Nov 26.</citation>
      <PMID>31776306</PMID>
    </reference>
    <reference>
      <citation>Al Moundhri MS, Al-Salam S, Al Mahrouqee A, Beegam S, Ali BH. The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, biochemical, and histopathological studies. J Med Toxicol. 2013 Mar;9(1):25-33. doi: 10.1007/s13181-012-0239-x.</citation>
      <PMID>22648527</PMID>
    </reference>
    <reference>
      <citation>Babu A, Prasanth KG, Balaji B. Effect of curcumin in mice model of vincristine-induced neuropathy. Pharm Biol. 2015 Jun;53(6):838-48. doi: 10.3109/13880209.2014.943247. Epub 2014 Nov 28.</citation>
      <PMID>25429779</PMID>
    </reference>
    <reference>
      <citation>Saghatelyan T, Tananyan A, Janoyan N, Tadevosyan A, Petrosyan H, Hovhannisyan A, Hayrapetyan L, Arustamyan M, Arnhold J, Rotmann AR, Hovhannisyan A, Panossian A. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2020 Apr 18;70:153218. doi: 10.1016/j.phymed.2020.153218. Online ahead of print.</citation>
      <PMID>32335356</PMID>
    </reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>April 7, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 21, 2023</last_update_submitted>
    <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Paclitaxel</keyword>
    <keyword>Curcumin</keyword>
    <keyword>Breast Cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Curcumin</mesh_term>
      <mesh_term>Paclitaxel</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05966441
  org study id: Paclitaxel induced PN
  nct id: NCT05966441
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  Paclitaxel induced peripheral neuropathy is the most common and serious side effect
        associated with Paclitaxel treatment in breast cancer patients receiving Paclitaxel.
  
        The efficacy of antioxidant molecules as neuroprotective strategies to preventing the
        development of peripheral neuropathy has been investigated in preclinical and clinical
        studies. Vitamin E and Glutathione have been explored as adjuvant therapies to preventing
        taxane-induced peripheral neuropathy. Other tested neuroprotective treatments with limited
        success include amifostine, glutamine and acetyl l-carnitine. Curcumin's antioxidant capacity
        is similar to other potent antioxidants, such as trolox (a vitamin E analog). Curcumin
        inhibits lipid peroxidation in different tissues, regulates intracellular levels of
        antioxidant enzymes (e.g., catalase, glutathione peroxidase and superoxide dismutase) and is
        an effective intracellular reactive oxygen species (ROS) scavenger.
  
        The investigators are going to investigate the neuroprotective effect of Curcumin against
        Paclitaxel induced peripheral neuropathy.
  The work is a prospective, randomized, open label controlled study. A total of 90 breast
        cancer female patients will be enrolled in the study. Eligible patients will simply be
        randomized using random allocation generator, after the end of anthracycline adjuvant therapy
        to one of two groups, Group I: will receive paclitaxel regimen plus 2g of curcumin Group II:
        will receive paclitaxel regimen only.
  
        The cases involved in the study will be recruited from Ain Shams Teaching Hospital.
  
        All patients presenting to the department were assessed for eligibility according to certain
        inclusion and exclusion criteria.
  
        Details of the research steps that the subscriber will be exposed to:
  
          -  Base line evaluation then alignment in either intervention or control group either for
             taking the interventional drug or standard of care in control group.
  
          -  Blood samples will be collected at baseline.
  
          -  Patient will be given a weekly supply of the medication and will be asked to take his
             prescribed dose daily.
  
          -  Every week all patients will be asked about their symptoms and if they experience any
             adverse drug reaction.
  
          -  Patients will receive the interventional drug until the last paclitaxel dose will be
             taken.
  
          -  After 3 months, another full clinical examination and blood sample will be obtained.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Details of the research steps that the subscriber will be exposed to:
  Base line evaluation then alignment in either intervention or control group either for taking the interventional drug or standard of care in control group.
  Blood samples will be collected at baseline.
  Patient will be given a weekly supply of the medication and will be asked to take his prescribed dose daily.
  Every week all patients will be asked about their symptoms and if they experience any adverse drug reaction.
  Patients will receive the interventional drug until the last paclitaxel dose will be taken.
  After 3 months, another full clinical examination and blood sample will be obtained.
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Evaluate the effect of Curcumin on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients.
  time frame: Baseline
  description: After each cycle, initial evaluation of response will be done guided by clinical examination and functional assessment and questionnaire.
  measure: Evaluate the effect of Curcumin on the damage of nerve fibers induced by paclitaxel.
  time frame: Baseline
  description: Nerve growth factor level will be obtained at day 0 and at the end of the paclitaxel course
  measure: Evaluate the effect of adding curcumin to paclitaxel-based chemotherapy on response rate in neoadjuvant therapy.
  time frame: baseline
  description: CT scan will be done before first dose of paclitaxel and at the end of the course
  arm group label: Experimental group
  arm group type: Experimental
  description: Patients will receive their Paclitaxel-based chemotherapy along with Curcumin at a dose of oral 2g daily till the end of chemotherapy.
  arm group label: Control group
  arm group type: Placebo Comparator
  description: Patients will receive their Paclitaxel-based chemotherapy only
  intervention type: Dietary Supplement
  intervention name: Curcumin
  description: The safety of curcumin has been widely demonstrated, and curcumin has a variety of potential pharmaceutical applications. Curcumin exhibits antioxidant, anti-inflammatory and anticancer properties and has been described as neuroprotective against neurological disorders.
  Many of curcumin's pharmacological benefits arise from its antioxidant or anti-inflammatory properties. Curcumin appears to have significant potential for treatment of diseases that result from oxidative stress.
  Curcumin is provided in soft gelatin capsules each capsule contains 1 g of curcumin and patient is asked to take 2 capsules daily
  arm group label: Control group
  arm group label: Experimental group
  intervention type: Drug
  intervention name: Paclitaxel
  description: Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer Paclitaxel dose in adjuvant therapy after doxorubicin and cyclophosphamide every 3 weeks 175mg/m2 IV or Weekly 80 mg/m2 IV..
  Paclitaxel dose in neoadjuvant therapy every 3 weeks 175 mg/m2 IV.
  arm group label: Control group
  arm group label: Experimental group
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Sherif Gawish, master student
  phone: 00201019700299
  email: sherif.gawish2020@gmail.com
  citation: Zhang X, Guan Z, Wang X, Sun D, Wang D, Li Y, Pei B, Ye M, Xu J, Yue X. Curcumin Alleviates Oxaliplatin-Induced Peripheral Neuropathic Pain through Inhibiting Oxidative Stress-Mediated Activation of NF-kappaB and Mitigating Inflammation. Biol Pharm Bull. 2020 Feb 1;43(2):348-355. doi: 10.1248/bpb.b19-00862. Epub 2019 Nov 26.
  PMID: 31776306
  citation: Al Moundhri MS, Al-Salam S, Al Mahrouqee A, Beegam S, Ali BH. The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, biochemical, and histopathological studies. J Med Toxicol. 2013 Mar;9(1):25-33. doi: 10.1007/s13181-012-0239-x.
  PMID: 22648527
  citation: Babu A, Prasanth KG, Balaji B. Effect of curcumin in mice model of vincristine-induced neuropathy. Pharm Biol. 2015 Jun;53(6):838-48. doi: 10.3109/13880209.2014.943247. Epub 2014 Nov 28.
  PMID: 25429779
  citation: Saghatelyan T, Tananyan A, Janoyan N, Tadevosyan A, Petrosyan H, Hovhannisyan A, Hayrapetyan L, Arustamyan M, Arnhold J, Rotmann AR, Hovhannisyan A, Panossian A. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2020 Apr 18;70:153218. doi: 10.1016/j.phymed.2020.153218. Online ahead of print.
  PMID: 32335356
  responsible party type: Sponsor
  mesh term: Peripheral Nervous System Diseases
  mesh term: Curcumin
  mesh term: Paclitaxel