<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/NCT03248193</url>
  </required_header>
  <id_info>
    <org_study_id>2017/00138</org_study_id>
    <nct_id>NCT03248193</nct_id>
  </id_info>
  <brief_title>Concomitant Limb Cryocompression and Scalp Cooling to Reduce Paclitaxel-induced Neuropathy and Alopecia</brief_title>
  <official_title>Concomitant Limb Cryocompression and Scalp Cooling to Reduce Paclitaxel-induced Neuropathy and Alopecia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National University Hospital, Singapore</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>
      Paclitaxel is a chemotherapy drug that is used to treat breast cancer, one of the most common&#xD;
      cancers. It causes two side effects very often - hair-loss and numbness. Until recently,&#xD;
      there have been no known ways to prevent or treat either side effect. Recently, cooling of&#xD;
      the scalp to prevent hair loss caused by paclitaxel was approved. Our team is developing a&#xD;
      method to prevent numbness caused by paclitaxel by using a device that cools the arms and the&#xD;
      legs, while applying mild pressure, and this technique is called cryocompression. As scalp&#xD;
      cooling use in day-to-day cancer care increases, future studies involving cryocompression to&#xD;
      treat neuropathy must take this into account, lest patients be denied or are required to&#xD;
      trade-off one treatment for the other. However, there is concern of causing a reduction in&#xD;
      core body temperature, which would not be safe or a general intolerance to this treatment.&#xD;
      Both scalp cooling and limb cryocompression individually have not shown to cause this, but&#xD;
      simultaneous use has not been studied previously. Clinical safety studies, in healthy&#xD;
      subjects and cancer patients would need to be conducted to prove this theory, which is being&#xD;
      proposed by currently.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Paclitaxel is a key chemotherapeutic agent used in the management of common cancers, such as&#xD;
      breast cancer. Chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel is a&#xD;
      common dose-limiting toxicity with no effective prevention or treatment. Limb cryocompression&#xD;
      is currently being developed as a method to reduce CIPN. Another common toxicity of&#xD;
      paclitaxel is chemotherapy induced alopecia (CIA), for which scalp-cooling is currently an&#xD;
      approved therapy to reduce the incidence of this adverse effect. As scalp cooling use in&#xD;
      day-to-day clinical practice increases, future studies involving hypothermia to treat&#xD;
      neuropathy must factor this into the treatment algorithm, lest patients be denied or are&#xD;
      required to trade-off one treatment for the other. However, there is concern of causing core&#xD;
      hypothermia and/or general intolerance to concomitant therapy. Both scalp-cooling and&#xD;
      cryocompression individually have not shown to cause this, but simultaneous use has not been&#xD;
      studied previously. Clinical safety studies, in healthy subjects and cancer patients would&#xD;
      need to be conducted first, before larger efficacy studies are performed. We propose that we&#xD;
      can deliver scalp-cooling and limb cryocompression with a single treatment modality to&#xD;
      prevent two toxicities of paclitaxel - CIA and CIPN. This study will consist of two parts: A)&#xD;
      Healthy subjects: To assess safety and tolerability of scalp and limb cryocompression, as&#xD;
      well as to determine the optimal temperature and pressure to be used, that will contribute to&#xD;
      the cryocompression protocol. The occurrence of core hypothermia or intolerance will be&#xD;
      closely monitored B) Cancer patients: Once the optimal cryocompression protocol is&#xD;
      established in healthy patients, a group of cancer patients will undergo concomitant limb&#xD;
      cryocompression and scalp cooling over multiple cycles of chemotherapy to establish safety&#xD;
      and tolerability of repeated therapy. Early clinical efficacy signal data will also be&#xD;
      collected, to prepare for the subsequent larger randomized efficacy study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 4, 2017</start_date>
  <completion_date type="Anticipated">April 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This study will consist of two parts:&#xD;
A) Healthy subjects: To assess safety and tolerability of scalp and limb hypothermia, as well as to determine the optimal temperature and pressure to be used. Establishing the occurrence or lack of core hypothermia will be studied.&#xD;
B) Cancer patients: Once the optimal temperature and pressure of scalp and limb hypothermia is established in healthy patients, a group of cancer patients will undergo concomitant scalp and limb hypothermia over multiple cycles of chemotherapy to establish safety and tolerability of repeated therapy.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Investigation of safety and tolerability of concomitant scalp cooling and limb cryocompression in healthy subjects: defined as the number of patients with treatment-related intolerance as assessed by CTCAE v4.0 and tolerability scales</measure>
    <time_frame>From the start of assessment until study completion, an average of 1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Investigation of safety and tolerability of concomitant scalp cooling and limb cryocompression in cancer patients: defined as the number of patients with treatment-related intolerance as assessed by CTCAE v4.0 and tolerability scales.</measure>
    <time_frame>From the start of assessment until study completion, an average of 1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in sensory nerve action potential on nerve conduction tests before and at the end of taxane-based chemotherapy with limb cryocompression.</measure>
    <time_frame>From the start of assessment until study completion, an average of 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in qualitative symptom scores before and at the end of taxane-based chemotherapy with limb cryocompression.</measure>
    <time_frame>From the start of assessment until study completion, an average of 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Chemotherapy-induced Peripheral Neuropathy (CIPN)</condition>
  <arm_group>
    <arm_group_label>Healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To assess safety and tolerability of scalp and limb hypothermia, as well as to determine the optimal temperature and pressure to be used. Establishing the occurrence or lack of core hypothermia will be studied.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cancer subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once the optimal temperature and pressure of scalp and limb hypothermia is established in healthy patients, a group of cancer patients will undergo concomitant scalp and limb hypothermia over multiple cycles of chemotherapy to establish safety and tolerability of repeated therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Concomitant limb cryocompression and scalp cooling</intervention_name>
    <description>Part 1: Establishing optimal temperature for hypothermia therapy. Healthy subjects will undergo 3 hours of cryocompression various temperature levels.&#xD;
Part 2: Establishing optimal pressure for hypothermia therapy. Each subject will undergo cryocompression (fixed at the lowest tolerated temperature established in Section 1) over 3 hours. The pressure ranges to be tested are either low, medium, or high.&#xD;
Part 3: Establishing safety and tolerability of scalp hypothermia. Scalp hypothermia will be administered over 3 hours using the cooling cap attached to the cooling device.&#xD;
Part 4: Establishing safety and tolerability of concomitant therapy. Subjects will undergo simultaneous scalp hypothermia and four-limb cryocompression at the temperature and pressure established in Sections 1 and 2. The concomitant therapy will be administered over 3 hours.</description>
    <arm_group_label>Healthy subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Concomitant limb cryocompression and scalp cooling</intervention_name>
    <description>The study population will comprise of cancer patients scheduled to receive weekly paclitaxel chemotherapy for a maximum of 12 cycles.&#xD;
Paclitaxel will be administered as a one-hour infusion. Concomitant scalp cooling and limb cryocompression sessions comprised of a pre-cooling period (one hour), continued with paclitaxel infusion and a post-cooling period (on average 30 minutes after the end of paclitaxel infusion). Overall, hypothermia will be administered for no longer than four hours.&#xD;
Cryocompression will be administered on patients based on the lowest tolerated temperature and optimal pressure as determined in healthy subjects.</description>
    <arm_group_label>Cancer subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        The inclusion criterion for the healthy subjects:&#xD;
&#xD;
          -  Age 21-80 years&#xD;
&#xD;
          -  Signed informed consent from patient.&#xD;
&#xD;
          -  No history of neuropathy&#xD;
&#xD;
          -  ECOG 0&#xD;
&#xD;
          -  No history of hospitalization in the past 6 months&#xD;
&#xD;
        The inclusion criteria for the cancer patients:&#xD;
&#xD;
          -  Age 21- 80 years.&#xD;
&#xD;
          -  Signed informed consent from patient&#xD;
&#xD;
          -  Scheduled to receive weekly paclitaxel chemotherapy&#xD;
&#xD;
        For both healthy subjects and cancer patients:&#xD;
&#xD;
          -  Open skin wound or ulcers of the limbs&#xD;
&#xD;
          -  A score of more than 5 in the Total Neuropathy Score (TNS) at baseline (see outcome&#xD;
             parameters) (Not applicable for healthy subjects)&#xD;
&#xD;
          -  History of Raynaud's phenomenon, peripheral vascular disease, or poorly controlled&#xD;
             diabetes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raghav Sundar</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University Hospital, Singapore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Raghav Sundar</last_name>
    <phone>(65) 6779 5555</phone>
    <email>raghav_sundar@nuhs.edu.sg</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joline Lim</last_name>
    <phone>(65) 6779 5555</phone>
    <email>joline_sj_lim@nuhs.edu.sg</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National University Hospital Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>119228</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raghav Sundar</last_name>
      <phone>+65 6779 5555</phone>
      <email>raghav_sundar@nuhs.edu.sg</email>
    </contact>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst. 2008 Mar;13(1):27-46. doi: 10.1111/j.1529-8027.2008.00156.x.</citation>
    <PMID>18346229</PMID>
  </reference>
  <reference>
    <citation>Sundar R, Bandla A, Tan SS, Liao LD, Kumarakulasinghe NB, Jeyasekharan AD, Ow SG, Ho J, Tan DS, Lim JS, Vijayan J, Therimadasamy AK, Hairom Z, Ang E, Ang S, Thakor NV, Lee SC, Wilder-Smith EP. Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study. Front Oncol. 2017 Jan 10;6:274. doi: 10.3389/fonc.2016.00274. eCollection 2016.</citation>
    <PMID>28119855</PMID>
  </reference>
  <reference>
    <citation>Bandla A, Sundar R, Liao LD, Sze Hui Tan S, Lee SC, Thakor NV, Wilder-Smith EP. Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls. Acta Oncol. 2016;55(4):430-6. doi: 10.3109/0284186X.2015.1075664. Epub 2015 Sep 11.</citation>
    <PMID>26360921</PMID>
  </reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>August 9, 2017</last_update_submitted>
  <last_update_submitted_qc>August 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>paclitaxel</keyword>
  <keyword>neuropathy</keyword>
  <keyword>hypothermia</keyword>
  <keyword>cryocompression</keyword>
  <keyword>alopecia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    <mesh_term>Alopecia</mesh_term>
    <mesh_term>Alopecia Areata</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/NCT03248193
org study id: 2017/00138
nct id: NCT03248193
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Paclitaxel is a chemotherapy drug that is used to treat breast cancer, one of the most common
      cancers. It causes two side effects very often - hair-loss and numbness. Until recently,
      there have been no known ways to prevent or treat either side effect. Recently, cooling of
      the scalp to prevent hair loss caused by paclitaxel was approved. Our team is developing a
      method to prevent numbness caused by paclitaxel by using a device that cools the arms and the
      legs, while applying mild pressure, and this technique is called cryocompression. As scalp
      cooling use in day-to-day cancer care increases, future studies involving cryocompression to
      treat neuropathy must take this into account, lest patients be denied or are required to
      trade-off one treatment for the other. However, there is concern of causing a reduction in
      core body temperature, which would not be safe or a general intolerance to this treatment.
      Both scalp cooling and limb cryocompression individually have not shown to cause this, but
      simultaneous use has not been studied previously. Clinical safety studies, in healthy
      subjects and cancer patients would need to be conducted to prove this theory, which is being
      proposed by currently.
Paclitaxel is a key chemotherapeutic agent used in the management of common cancers, such as
      breast cancer. Chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel is a
      common dose-limiting toxicity with no effective prevention or treatment. Limb cryocompression
      is currently being developed as a method to reduce CIPN. Another common toxicity of
      paclitaxel is chemotherapy induced alopecia (CIA), for which scalp-cooling is currently an
      approved therapy to reduce the incidence of this adverse effect. As scalp cooling use in
      day-to-day clinical practice increases, future studies involving hypothermia to treat
      neuropathy must factor this into the treatment algorithm, lest patients be denied or are
      required to trade-off one treatment for the other. However, there is concern of causing core
      hypothermia and/or general intolerance to concomitant therapy. Both scalp-cooling and
      cryocompression individually have not shown to cause this, but simultaneous use has not been
      studied previously. Clinical safety studies, in healthy subjects and cancer patients would
      need to be conducted first, before larger efficacy studies are performed. We propose that we
      can deliver scalp-cooling and limb cryocompression with a single treatment modality to
      prevent two toxicities of paclitaxel - CIA and CIPN. This study will consist of two parts: A)
      Healthy subjects: To assess safety and tolerability of scalp and limb cryocompression, as
      well as to determine the optimal temperature and pressure to be used, that will contribute to
      the cryocompression protocol. The occurrence of core hypothermia or intolerance will be
      closely monitored B) Cancer patients: Once the optimal cryocompression protocol is
      established in healthy patients, a group of cancer patients will undergo concomitant limb
      cryocompression and scalp cooling over multiple cycles of chemotherapy to establish safety
      and tolerability of repeated therapy. Early clinical efficacy signal data will also be
      collected, to prepare for the subsequent larger randomized efficacy study.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: This study will consist of two parts:
A) Healthy subjects: To assess safety and tolerability of scalp and limb hypothermia, as well as to determine the optimal temperature and pressure to be used. Establishing the occurrence or lack of core hypothermia will be studied.
B) Cancer patients: Once the optimal temperature and pressure of scalp and limb hypothermia is established in healthy patients, a group of cancer patients will undergo concomitant scalp and limb hypothermia over multiple cycles of chemotherapy to establish safety and tolerability of repeated therapy.
primary purpose: Prevention
masking: None (Open Label)
measure: Investigation of safety and tolerability of concomitant scalp cooling and limb cryocompression in healthy subjects: defined as the number of patients with treatment-related intolerance as assessed by CTCAE v4.0 and tolerability scales
time frame: From the start of assessment until study completion, an average of 1 year
measure: Investigation of safety and tolerability of concomitant scalp cooling and limb cryocompression in cancer patients: defined as the number of patients with treatment-related intolerance as assessed by CTCAE v4.0 and tolerability scales.
time frame: From the start of assessment until study completion, an average of 1 year
measure: Difference in sensory nerve action potential on nerve conduction tests before and at the end of taxane-based chemotherapy with limb cryocompression.
time frame: From the start of assessment until study completion, an average of 2 years
measure: Difference in qualitative symptom scores before and at the end of taxane-based chemotherapy with limb cryocompression.
time frame: From the start of assessment until study completion, an average of 2 years
arm group label: Healthy subjects
arm group type: Experimental
description: To assess safety and tolerability of scalp and limb hypothermia, as well as to determine the optimal temperature and pressure to be used. Establishing the occurrence or lack of core hypothermia will be studied.
arm group label: Cancer subjects
arm group type: Experimental
description: Once the optimal temperature and pressure of scalp and limb hypothermia is established in healthy patients, a group of cancer patients will undergo concomitant scalp and limb hypothermia over multiple cycles of chemotherapy to establish safety and tolerability of repeated therapy.
intervention type: Device
intervention name: Concomitant limb cryocompression and scalp cooling
description: Part 1: Establishing optimal temperature for hypothermia therapy. Healthy subjects will undergo 3 hours of cryocompression various temperature levels.
Part 2: Establishing optimal pressure for hypothermia therapy. Each subject will undergo cryocompression (fixed at the lowest tolerated temperature established in Section 1) over 3 hours. The pressure ranges to be tested are either low, medium, or high.
Part 3: Establishing safety and tolerability of scalp hypothermia. Scalp hypothermia will be administered over 3 hours using the cooling cap attached to the cooling device.
Part 4: Establishing safety and tolerability of concomitant therapy. Subjects will undergo simultaneous scalp hypothermia and four-limb cryocompression at the temperature and pressure established in Sections 1 and 2. The concomitant therapy will be administered over 3 hours.
arm group label: Healthy subjects
intervention type: Device
intervention name: Concomitant limb cryocompression and scalp cooling
description: The study population will comprise of cancer patients scheduled to receive weekly paclitaxel chemotherapy for a maximum of 12 cycles.
Paclitaxel will be administered as a one-hour infusion. Concomitant scalp cooling and limb cryocompression sessions comprised of a pre-cooling period (one hour), continued with paclitaxel infusion and a post-cooling period (on average 30 minutes after the end of paclitaxel infusion). Overall, hypothermia will be administered for no longer than four hours.
Cryocompression will be administered on patients based on the lowest tolerated temperature and optimal pressure as determined in healthy subjects.
arm group label: Cancer subjects
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Raghav Sundar
role: Principal Investigator
affiliation: National University Hospital, Singapore
last name: Raghav Sundar
phone: (65) 6779 5555
email: raghav_sundar@nuhs.edu.sg
last name: Joline Lim
phone: (65) 6779 5555
email: joline_sj_lim@nuhs.edu.sg
facility: 
status: Recruiting
contact: 
country: Singapore
citation: Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst. 2008 Mar;13(1):27-46. doi: 10.1111/j.1529-8027.2008.00156.x.
PMID: 18346229
citation: Sundar R, Bandla A, Tan SS, Liao LD, Kumarakulasinghe NB, Jeyasekharan AD, Ow SG, Ho J, Tan DS, Lim JS, Vijayan J, Therimadasamy AK, Hairom Z, Ang E, Ang S, Thakor NV, Lee SC, Wilder-Smith EP. Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study. Front Oncol. 2017 Jan 10;6:274. doi: 10.3389/fonc.2016.00274. eCollection 2016.
PMID: 28119855
citation: Bandla A, Sundar R, Liao LD, Sze Hui Tan S, Lee SC, Thakor NV, Wilder-Smith EP. Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls. Acta Oncol. 2016;55(4):430-6. doi: 10.3109/0284186X.2015.1075664. Epub 2015 Sep 11.
PMID: 26360921
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
mesh term: Alopecia
mesh term: Alopecia Areata
sharing ipd: No