<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/NCT03272919</url>
  </required_header>
  <id_info>
    <org_study_id>5170197</org_study_id>
    <nct_id>NCT03272919</nct_id>
  </id_info>
  <brief_title>Chemotherapy Induced Peripheral Neuropathy (CIPN)</brief_title>
  <official_title>Chemotherapy Induced Peripheral Neuropathy (CIPN): A Pilot Study of Intraneural Facilitation for Managing Chemotherapy-Induced Peripheral Neuropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loma Linda University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Loma Linda University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect of many forms of&#xD;
      chemotherapy having a negative impact on the quality of life for cancer survivors due to&#xD;
      numbness, decreased sensation, pain (of various intensities in the extremities), gait/balance&#xD;
      problems, and difficulty with fine motor skills of the hands and fingers.To date, there are&#xD;
      no preventive modalities to mitigate CIPN development.When CIPN becomes intolerable, optimal&#xD;
      doses of chemotherapy have to be reduced or discontinued, which may affect a patient's&#xD;
      overall survival. Intraneural facilitation (INF) is a technique developed by physical&#xD;
      therapists at Loma Linda University after careful study of the structure, pathophysiology and&#xD;
      biomechanics of peripheral nerves. The focus of INF is restoration of circulation to an&#xD;
      ischemic nerve. INF has been offered to subjects receiving treatment at LLUCC with anecdotal&#xD;
      success. The purpose of this study is to evaluate INF as a treatment modality under the rigor&#xD;
      of scientific inquiry to determine its effectiveness as a viable treatment option for breast&#xD;
      cancer patients with CIPN.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY OUTLINE: This is a single institution study. Patients with newly diagnosed breast&#xD;
      cancer stages I to III with any biomarker status (ER, PR and HER), without preexisting&#xD;
      peripheral neuropathy planning to receive treatment with platinum-based compounds&#xD;
      (Carboplatin and Cisplatin) and/or taxanes (Docetaxel and Paclitaxel) and chemotherapy naive&#xD;
      patients with gynecologic cancers including ovarian, uterine, and cervical cancer planning to&#xD;
      receive definitive number of platinum-based compounds (carboplatin or cisplatin) and/or&#xD;
      taxanes (docetaxel and paclitaxel) chemotherapy are potential study patients.&#xD;
&#xD;
      Subjects will be randomized into one of two treatment arms within 3 weeks of starting the&#xD;
      offending chemotherapy agents after fulfilling the other study eligibility requirements. Arm&#xD;
      1 (investigational) will receive INF twice a week for six weeks by the same treating physical&#xD;
      therapist (physical therapist #1). Arm 2 (control) will receive a standardized program of&#xD;
      muscle stretching and strengthening exercises twice a week for 6 weeks under the supervision&#xD;
      of treating physical therapist #1. Actual treatment time for both modalities is approximately&#xD;
      45 minutes. Measurements used to detect the presence and degree of peripheral neuropathy will&#xD;
      be administered by the same assessment physical therapist (physical therapist #2) at baseline&#xD;
      and at the end of weeks 3, 6, and 3 months post last physical therapy treatment. Assessment&#xD;
      tools are: ultrasound imaging on the popliteal and posterior tibia artery, the 20-item Pain&#xD;
      Quality Assessment Scale (PQAS, specifically addresses neuropathological symptomatology), the&#xD;
      National Comprehensive Cancer Network (NCCN) Distress thermometer (DT), and the Michigan&#xD;
      Neuropathy Screening Instrument (MNSI) will be assessed and recorded along with treatment&#xD;
      adherence. Treating physician will be recording National Cancer Institute Common Terminology&#xD;
      Criteria for Adverse Events (CTCAE) neuropathy score and performance status at routine&#xD;
      intervals during and after chemotherapy.&#xD;
&#xD;
      Objectives&#xD;
&#xD;
      Primary objective&#xD;
&#xD;
      • To compare the degree of neuropathy and distress between Arm 1 receiving INF therapy&#xD;
      compared to Arm 2 receiving usual care of muscle stretching and strengthening exercises based&#xD;
      on standardized measurements (PQAS, MNSI, NCCN DT, and AE assessment).&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
        -  To compare the Ultrasound measurements of peak systolic velocity, volume flow and&#xD;
           pulsatility of popliteal and posterior tibia artery between the two treatment arms for&#xD;
           assessing differences in vascular perfusion.&#xD;
&#xD;
        -  To compare the rate of any dose reductions and premature chemotherapy discontinuation&#xD;
           rates due to peripheral neuropathy between Arm 1 receiving INF therapy compared to Arm 2&#xD;
           receiving standardized program of muscle stretching and strengthening exercises.&#xD;
&#xD;
        -  To compare subject acceptability, burden and satisfaction with the assigned physical&#xD;
           therapy modality between the two arms based on patient satisfaction questionnaire&#xD;
           administered at the end of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 28, 2017</start_date>
  <completion_date type="Actual">May 25, 2022</completion_date>
  <primary_completion_date type="Actual">May 25, 2022</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Descriptive Statistics to measure the degree of peripheral neuropathy in the two arms based on the PQAS score.</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>The 20 item PQAS measures self reported aspects of nociceptive and neuropathic pain (intensity, sensation, depth, location) on a scale of 0 to 10.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Descriptive Statistics to measure the degree of distress in the two arms based on NCCN- DT</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>Study participants self report distress based on National Comprehensive Cancer Network's Distress Thermometer (DT) measures distress on a scale of 0 = no distress, 10=extreme distress.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Descriptive Statistics to measure the degree of peripheral neuropathy in the two arms based on MSNI scores</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>The MSNI is a physical screening instrument of the lower legs and feet for the assessment of neuropathy using visual inspection, vibration sensation, ankle reflexes and monofilament testing producing a score of 0 being normal and 10 meaning significant neuropathy as measured by the assessing physical therapist</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Descriptive Statistics to measure the degree of peripheral neuropathy in the two arms based on CTCAE grading</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>The CTCAE measures peripheral sensory neuropathy on a scale of 1=asymptomatic to 5=death as measured by the treating physician</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure the peak systolic velocity on ultrasound imaging in the popliteal and posterior tibia artery in the two arms.</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>Ultrasound imaging will be administered before and after treatment on the measurement days for subjects in both Arm 1 and Arm 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure the rate of premature chemotherapy discontinuation due to peripheral neuropathy by treatment group</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>The completion and premature discontinuation rates due to peripheral neuropathy for each subject will be counted for each Arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure the rate of dose reductions in chemotherapy due to peripheral neuropathy by treatment group</measure>
    <time_frame>upto 3 months post completion of assigned treatment</time_frame>
    <description>The dose reductions in chemotherapy due to peripheral neuropathy for each subject will be measured for each Arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Questionnaire to survey patients on acceptability, satisfaction and burden of treatment</measure>
    <time_frame>upto 3 months post completion of assigned treatment.</time_frame>
    <description>A written survey of 10 questions regarding subject acceptance, burden and satisfaction will be administered to each subject in both Arms at the end of treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Chemotherapy-induced Peripheral Neuropathy</condition>
  <arm_group>
    <arm_group_label>Arm 1: Investigational INF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intraneural Facilitation (INF) treatment is an effective way to restore blood flow to damaged nerves as neuropathy is strongly impacted by reduced blood flow.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: Standardized muscle stretching and strengthen</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>subjects will receive a standardized program of muscle stretching and strengthening exercise twice a week for six weeks under the supervision of treating physical therapist</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Arm 1: Investigational INF</intervention_name>
    <description>INF utilizes three holds or positions, which widens tiny openings in arteries surrounding nerves and improves blood flow to targeted nerves. The improved blood flow in these nerves stimulates healing and reduces or even stops nerve pain.</description>
    <arm_group_label>Arm 1: Investigational INF</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Arm 2: standardized muscle stretching and strength</intervention_name>
    <description>subjects will receive a standardized program of muscle stretching and strengthening exercise under the supervision of treating physical therapist.</description>
    <arm_group_label>Arm 2: Standardized muscle stretching and strengthen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed stages I to III breast cancer patients with any biomarker status (ER,&#xD;
             PR and HER) receiving treatment with platinum-based compounds (Carboplatin and&#xD;
             Cisplatin) and/or taxanes (Docetaxel and Paclitaxel).&#xD;
&#xD;
          -  Chemotherapy naive patients with gynecologic cancers including ovarian, uterine, and&#xD;
             cervical cancer planning to receive definitive number of platinum-based compounds&#xD;
             (carboplatin or cisplatin) and/or taxanes (docetaxel and paclitaxel) chemotherapy.&#xD;
&#xD;
          -  Planned to receive a minimum of 4 cycles of treatment with either of the offending&#xD;
             chemotherapy agents (a cycle of weekly paclitaxel is considered 3 doses).&#xD;
&#xD;
          -  Women aged ≥ 18 years at signing of informed consent&#xD;
&#xD;
          -  No pre-existing peripheral neuropathy (WPPN)&#xD;
&#xD;
          -  ECOG status 0 or 1&#xD;
&#xD;
          -  Able to provide written, informed consent to participate in the study and follow the&#xD;
             study procedures.&#xD;
&#xD;
          -  Cannot participate in another non-medical intervention/therapy for peripheral&#xD;
             neuropathy&#xD;
&#xD;
          -  Cannot receive more than 3 weeks of treatment with implicating chemotherapy prior to&#xD;
             start of study assigned therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Preexisting peripheral neuropathy.&#xD;
&#xD;
          -  Previous exposure to any of the implicated chemotherapy agents within the last 5 years&#xD;
             (platinum-based compounds, vinca alkaloids and/or taxanes) that could potentially&#xD;
             cause peripheral neuropathy&#xD;
&#xD;
          -  Evidence of significant medical illness, or psychiatric illness/social situation that&#xD;
             would, in the investigator's judgment, make the patient inappropriate for this study.&#xD;
&#xD;
          -  Stage IV or metastatic breast cancer&#xD;
&#xD;
          -  Any physical or neurological disability that would preclude patients from&#xD;
             participating in physical therapy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Women aged ≥ 18 years at signing of informed consent</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gayathri Nagaraj, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loma Linda University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ellen D'Errico, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loma Linda University School of Nursing</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loma Linda Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loma Linda University</investigator_affiliation>
    <investigator_full_name>Gayathri Nagaraj</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer, Peripheral neuropathy, Taxol, carboplatin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
  </condition_browse>
  <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/NCT03272919
org study id: 5170197
nct id: NCT03272919
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect of many forms of
      chemotherapy having a negative impact on the quality of life for cancer survivors due to
      numbness, decreased sensation, pain (of various intensities in the extremities), gait/balance
      problems, and difficulty with fine motor skills of the hands and fingers.To date, there are
      no preventive modalities to mitigate CIPN development.When CIPN becomes intolerable, optimal
      doses of chemotherapy have to be reduced or discontinued, which may affect a patient's
      overall survival. Intraneural facilitation (INF) is a technique developed by physical
      therapists at Loma Linda University after careful study of the structure, pathophysiology and
      biomechanics of peripheral nerves. The focus of INF is restoration of circulation to an
      ischemic nerve. INF has been offered to subjects receiving treatment at LLUCC with anecdotal
      success. The purpose of this study is to evaluate INF as a treatment modality under the rigor
      of scientific inquiry to determine its effectiveness as a viable treatment option for breast
      cancer patients with CIPN.
STUDY OUTLINE: This is a single institution study. Patients with newly diagnosed breast
      cancer stages I to III with any biomarker status (ER, PR and HER), without preexisting
      peripheral neuropathy planning to receive treatment with platinum-based compounds
      (Carboplatin and Cisplatin) and/or taxanes (Docetaxel and Paclitaxel) and chemotherapy naive
      patients with gynecologic cancers including ovarian, uterine, and cervical cancer planning to
      receive definitive number of platinum-based compounds (carboplatin or cisplatin) and/or
      taxanes (docetaxel and paclitaxel) chemotherapy are potential study patients.

      Subjects will be randomized into one of two treatment arms within 3 weeks of starting the
      offending chemotherapy agents after fulfilling the other study eligibility requirements. Arm
      1 (investigational) will receive INF twice a week for six weeks by the same treating physical
      therapist (physical therapist #1). Arm 2 (control) will receive a standardized program of
      muscle stretching and strengthening exercises twice a week for 6 weeks under the supervision
      of treating physical therapist #1. Actual treatment time for both modalities is approximately
      45 minutes. Measurements used to detect the presence and degree of peripheral neuropathy will
      be administered by the same assessment physical therapist (physical therapist #2) at baseline
      and at the end of weeks 3, 6, and 3 months post last physical therapy treatment. Assessment
      tools are: ultrasound imaging on the popliteal and posterior tibia artery, the 20-item Pain
      Quality Assessment Scale (PQAS, specifically addresses neuropathological symptomatology), the
      National Comprehensive Cancer Network (NCCN) Distress thermometer (DT), and the Michigan
      Neuropathy Screening Instrument (MNSI) will be assessed and recorded along with treatment
      adherence. Treating physician will be recording National Cancer Institute Common Terminology
      Criteria for Adverse Events (CTCAE) neuropathy score and performance status at routine
      intervals during and after chemotherapy.

      Objectives

      Primary objective

      • To compare the degree of neuropathy and distress between Arm 1 receiving INF therapy
      compared to Arm 2 receiving usual care of muscle stretching and strengthening exercises based
      on standardized measurements (PQAS, MNSI, NCCN DT, and AE assessment).

      Secondary objectives

        -  To compare the Ultrasound measurements of peak systolic velocity, volume flow and
           pulsatility of popliteal and posterior tibia artery between the two treatment arms for
           assessing differences in vascular perfusion.

        -  To compare the rate of any dose reductions and premature chemotherapy discontinuation
           rates due to peripheral neuropathy between Arm 1 receiving INF therapy compared to Arm 2
           receiving standardized program of muscle stretching and strengthening exercises.

        -  To compare subject acceptability, burden and satisfaction with the assigned physical
           therapy modality between the two arms based on patient satisfaction questionnaire
           administered at the end of treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Descriptive Statistics to measure the degree of peripheral neuropathy in the two arms based on the PQAS score.
time frame: upto 3 months post completion of assigned treatment
description: The 20 item PQAS measures self reported aspects of nociceptive and neuropathic pain (intensity, sensation, depth, location) on a scale of 0 to 10.
measure: Descriptive Statistics to measure the degree of distress in the two arms based on NCCN- DT
time frame: upto 3 months post completion of assigned treatment
description: Study participants self report distress based on National Comprehensive Cancer Network's Distress Thermometer (DT) measures distress on a scale of 0 = no distress, 10=extreme distress.
measure: Descriptive Statistics to measure the degree of peripheral neuropathy in the two arms based on MSNI scores
time frame: upto 3 months post completion of assigned treatment
description: The MSNI is a physical screening instrument of the lower legs and feet for the assessment of neuropathy using visual inspection, vibration sensation, ankle reflexes and monofilament testing producing a score of 0 being normal and 10 meaning significant neuropathy as measured by the assessing physical therapist
measure: Descriptive Statistics to measure the degree of peripheral neuropathy in the two arms based on CTCAE grading
time frame: upto 3 months post completion of assigned treatment
description: The CTCAE measures peripheral sensory neuropathy on a scale of 1=asymptomatic to 5=death as measured by the treating physician
measure: Measure the peak systolic velocity on ultrasound imaging in the popliteal and posterior tibia artery in the two arms.
time frame: upto 3 months post completion of assigned treatment
description: Ultrasound imaging will be administered before and after treatment on the measurement days for subjects in both Arm 1 and Arm 2
measure: Measure the rate of premature chemotherapy discontinuation due to peripheral neuropathy by treatment group
time frame: upto 3 months post completion of assigned treatment
description: The completion and premature discontinuation rates due to peripheral neuropathy for each subject will be counted for each Arm.
measure: Measure the rate of dose reductions in chemotherapy due to peripheral neuropathy by treatment group
time frame: upto 3 months post completion of assigned treatment
description: The dose reductions in chemotherapy due to peripheral neuropathy for each subject will be measured for each Arm.
measure: Questionnaire to survey patients on acceptability, satisfaction and burden of treatment
time frame: upto 3 months post completion of assigned treatment.
description: A written survey of 10 questions regarding subject acceptance, burden and satisfaction will be administered to each subject in both Arms at the end of treatment.
arm group label: Arm 1: Investigational INF
arm group type: Experimental
description: Intraneural Facilitation (INF) treatment is an effective way to restore blood flow to damaged nerves as neuropathy is strongly impacted by reduced blood flow.
arm group label: Arm 2: Standardized muscle stretching and strengthen
arm group type: Other
description: subjects will receive a standardized program of muscle stretching and strengthening exercise twice a week for six weeks under the supervision of treating physical therapist
intervention type: Other
intervention name: Arm 1: Investigational INF
description: INF utilizes three holds or positions, which widens tiny openings in arteries surrounding nerves and improves blood flow to targeted nerves. The improved blood flow in these nerves stimulates healing and reduces or even stops nerve pain.
arm group label: Arm 1: Investigational INF
intervention type: Other
intervention name: Arm 2: standardized muscle stretching and strength
description: subjects will receive a standardized program of muscle stretching and strengthening exercise under the supervision of treating physical therapist.
arm group label: Arm 2: Standardized muscle stretching and strengthen
criteria: 
gender: Female
gender based: Yes
gender description: Women aged ≥ 18 years at signing of informed consent
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gayathri Nagaraj, MD
role: Principal Investigator
affiliation: Loma Linda University Medical Center
last name: Ellen D'Errico, PHD
role: Principal Investigator
affiliation: Loma Linda University School of Nursing
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Loma Linda University
investigator full name: Gayathri Nagaraj
investigator title: Associate Professor of Medicine
mesh term: Peripheral Nervous System Diseases
sharing ipd: No