<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/NCT04498208</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-57570</org_study_id>
    <nct_id>NCT04498208</nct_id>
  </id_info>
  <brief_title>Immune Modulation by Enhanced vs Standard Prehabilitation Program Before Major Surgery</brief_title>
  <official_title>Immune System Modulation by Enhanced vs Standard Prehabilitation Program in Patients Undergoing Elective Major Surgery - a Prospective Monocentric Randomized Single-blinded Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford 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>
      Over 30 million surgeries are performed annually in the US. Up to 30% of surgical patients&#xD;
      experience delayed surgical recovery, marked by prolonged post-surgical pain, opioid&#xD;
      consumption, and functional impairment, which contributes $8 billion annually to US health&#xD;
      care costs. Novel interventions that improve the resolution of pain, minimize opioid&#xD;
      exposure, and accelerate functional recovery after surgery are urgently needed.&#xD;
&#xD;
      Multi-modal pre-operative optimization programs (or &quot;prehab&quot;) integrating exercise,&#xD;
      nutrition, and stress reduction have been shown to safely and effectively improve outcomes&#xD;
      after surgery. However, no objective biological markers assess prehab effectiveness and are&#xD;
      able to tailor prehab programs to individual patients. Surgery is a profound immunological&#xD;
      perturbation, during which a complex network of innate and adaptive immune cells is mobilized&#xD;
      to organize the recovery process of wound healing, tissue repair, and pain resolution. As&#xD;
      such, the in-depth assessment of a patient's immune system before surgery is a promising&#xD;
      approach to tailor prehab programs to modifiable biological markers associated with surgical&#xD;
      recovery. The primary goal of this clinical trial is to determine the effect of a&#xD;
      personalized prehab program on patients immunological status before surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study design is a prospective monocenter single-blinded randomized controlled trial in&#xD;
      patients undergoing elective major abdominal surgery.&#xD;
&#xD;
        -  Patients will be recruited during the surgical consultation, at least 14 days prior to&#xD;
           surgery. If they choose to enroll, they will undergo randomization on the day of&#xD;
           enrollment.&#xD;
&#xD;
        -  Prehabilitation (Day 0): personalized or standard prehabilitation program will be&#xD;
           proposed to the patients for a period of 2 to 6 weeks. Immunological, nutritional,&#xD;
           physical, cognitive, anxiety and quality of life status will be quantified at baseline&#xD;
           by previously trained personnel.&#xD;
&#xD;
        -  From the beginning (Day 0) to the end of the prehabilitation program (Day 14 to Day 42):&#xD;
           every 7 days, a compliance questionnaire will be filled by phone, by a trained member of&#xD;
           the research team blinded to the treatment arm of the study&#xD;
&#xD;
        -  End of the prehabilitation period (Day 14 to Day 42): Immunological, nutritional,&#xD;
           physical, cognitive and anxiety status after prehabilitation will be recorded by a&#xD;
           trained member of the research team blinded to the treatment arm of the study.&#xD;
&#xD;
        -  Surgery (Day S)&#xD;
&#xD;
        -  Post operative period&#xD;
&#xD;
             -  From Day S (2 hours after surgery end) to discharge from the hospital, length of&#xD;
                stay, pain and adverse clinical events will be measured and recorded.&#xD;
&#xD;
             -  Immunological status will be assessed at Day S+1 by blood draw.&#xD;
&#xD;
             -  Cognitive function, neuropathic pain and quality of life will be assessed at Day S&#xD;
                + 30.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 7, 2020</start_date>
  <completion_date type="Anticipated">March 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2023</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>Supportive Care</primary_purpose>
    <masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite immunological score</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Composite immunological score containing a combination of blood immune cell frequencies and intracellular signaling responses. This score will be normalized to &quot;baseline&quot; (i.e. before prehabilitation) score for each patient.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of compliant patients</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Patient's compliance to prehabilitation programs will be evaluated using a modified Rehabilitation Adherence Measure scale, that will be filled by phone every 7 days during the prehabilitation program, i.e. 2 to 6 times by patient. Compliant patient will be defined by a mean score &gt;= 8/10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 Min Walk Test</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Changes in physical status will be examined using 6 Min Walk Test. The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timed Up and Go Test</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Changes in physical status will be examined using Timed Up and Go Test. The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Five Times Sit to Stand Test</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Changes in physical status will be examined using Five Times Sit to Stand Test. The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wall Squat Test</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Changes in physical status will be examined using Wall Squat Test. The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Body Mass Index will be recorded. The evaluation should be based on differences between pre- and post prehabilitation performance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amsterdam Preoperative Anxiety and Information Scale</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Prevalence and global severity of anxiety will be evaluated using the APAIS (Amsterdam Preoperative Anxiety and Information Scale). The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Catastrophizing Scale</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Prevalence and global severity of anxiety will be evaluated using the Pain Catastrophizing Scale. The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in diet</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Mediterranean Diet Score will be collected. The evaluation should be based on differences between pre- and post prehabilitation performance. A high intake of Mediterranean foods: cereals, legumes, fruit, vegetables, fish, Mon-unsaturated fatty acids to Saturated fatty acids (M/S) ratio, and wine were scored positive (1) and a high intake of the non-Mediterranean foods: dairy and meat negative (0). The score ranged from 0 to 9 and the higher the score the better the compliance to a traditional Mediterranean diet.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cognitive functions</measure>
    <time_frame>immediately preoperatively</time_frame>
    <description>Cognitive functions will evaluated by the qMCI test. The evaluation should be based on differences between pre- and post prehabilitation performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of postoperative complications</measure>
    <time_frame>Postoperatively through to 30 days after surgery</time_frame>
    <description>Postoperative complications will be scored by the Comprehensive Complication Index. The Comprehensive Complication Index (CCI®) is based on the complication grading by Clavien-Dindo Classification and implements every occurred complication after an intervention. The overall morbidity is reflected on a scale from 0 (no complication) to 100 (death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain</measure>
    <time_frame>Postoperatively through to 7 days after surgery</time_frame>
    <description>Pain scores will be assessed daily by the patient-reported Visual Analog Scale. Visual analog scale to assess the perceived stress on a horizontal, non-calibrated line of 10 cm, ranging from very low (0) to very high (10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative opioid consumption</measure>
    <time_frame>Postoperatively through to day 7</time_frame>
    <description>Cumulative opioid consumption will be obtained from the patients' charts up to 7 days after surgery or discharge from hospital if earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropathic pain</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>Neuropathic pain will be measured by the Patient Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality scale (PROMIS-PQ-Neuro). The questionnaire contains 5 items questions. Scores are based on patient responses to questions about pain intensity. 0 indicates no pain; 5 indicates the most pain imaginable. The total score may be up to 25.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>Hospital length of stay assessed from patients' medical administrative data in days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in quality of life</measure>
    <time_frame>30 days after surgery</time_frame>
    <description>Quality of life evaluated thanks to the SF-36 scale is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. Results will be normalized on &quot;baseline&quot; (before prehab) scores.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Surgery</condition>
  <condition>Immune System and Related Disorders</condition>
  <condition>Preoperative Care</condition>
  <condition>Gastrointestinal Disease</condition>
  <condition>Urological Disease</condition>
  <condition>Gynecologic Disease</condition>
  <condition>Thoracic Diseases</condition>
  <arm_group>
    <arm_group_label>Personalized prehabilitation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will participate in a personalized health optimization program combining one-on-one coaching, tailored to each patient's physical, nutritional, well-being and cognitive status baseline. Prehabilitation will last from a minimum of 14 days to a maximum of 42 days before surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard prehabilitation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in the control group will be provided with standard instructions in a hard-copy form specific to prehabilitation before surgery associating physical, nutritional, stress-reduction and cognitive recommendations without any personalized coaching for at least 14 days prior to surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Physical Prehabilitation</intervention_name>
    <description>First, an evaluation of patient's aerobic capacity, functional mobility, functional strength, ambulation, fall risk, and overall mobility will be done by a trained member of the research team. Based on their functional level and preexisting conditions, therapeutic exercises will be recommended to optimize their strength, endurance, flexibility, and functional mobility in preparation for surgery. Decisions about the interventions are based on the assessment, individual patient characteristics, environmental factors, surgical type, and monitoring of the client's response and progress. Weekly sessions are 30-45 minutes long to monitor the client's response and progress their program. Based on their response to exercise (evaluated also by 2 apps: Timed Walk App and Smart Metronome &amp; Tuner App), re-evaluation via the assessments described above, change their plan of care (alter frequency, resistance, exercises) or discontinuation of treatment could be decided.</description>
    <arm_group_label>Personalized prehabilitation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Stress Reduction Prehabilitation</intervention_name>
    <description>Participants will have the opportunity to learn techniques for mindfulness that have been established to reduce stress and assist with pain management with a member of the research team. Patients will be offered to listen to audio recording of relaxation sessions. Each session contains a relaxation technique that the patient practices while listening to the recording. Then the technique is used the next as a baseline to introduce a new technique more advanced. For some patients who struggle with the techniques the program will be adapted. Patients will choose 2 or 3 techniques and work on them.</description>
    <arm_group_label>Personalized prehabilitation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive Prehabilitation</intervention_name>
    <description>Cognitive prehabilitation will consist on the daily use of Lumosity training program, an already existing free app built to increase memory skills. The program proposed by Lumosity is tailored to each patient. The use of Lumosity will be monitored at each in-person session. Patients will be expected to complete at least three 5-minute sessions of Lumosity training per day.</description>
    <arm_group_label>Personalized prehabilitation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Nutrition Prehabilitation</intervention_name>
    <description>Nutrition prehabilitation will involve transitioning the patient to the Mediterranean diet with targets regarding hydration and the proportion of fruits, vegetables, whole grains, and healthy fats the patient will consume in a given day. This nutritional program is flexible, and it allows for specific physician and nutritionist-recommended dietary needs to be incorporated. The patient is also given tools to encourage success in healthier eating, including recipes, sample menus, healthy restaurant options, meal kit options, and local CSA box options</description>
    <arm_group_label>Personalized prehabilitation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (≥ 18 years)&#xD;
&#xD;
          -  Competent to provide informed consent&#xD;
&#xD;
          -  Undergoing major elective surgery under general anesthesia in ≥14 days from enrollment&#xD;
             (abdominal, thoracic, plastic and neurosurgeries).&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Premorbid conditions or orthopedic impairments with contraindications to exercise&#xD;
&#xD;
          -  Cognitive disabilities defined as evolutive neurological or neurodegenerative disease&#xD;
&#xD;
          -  ASA score 4 or higher or patient under palliative care&#xD;
&#xD;
          -  Illiteracy (inability to read the English language).&#xD;
&#xD;
          -  Expected length of stay at hospital &lt; 48 hours&#xD;
&#xD;
          -  Patient under tutorship or curatorship&#xD;
&#xD;
          -  Pregnant or breast-feeding woman&#xD;
&#xD;
          -  Absence of informed consent or request to not participate to the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brice Gaudilliere, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cindy Kin, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Brice Gaudilliere, MD, PhD</last_name>
    <phone>617 230 5927</phone>
    <email>gbrice@stanford.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cindy Kin, MD, MS</last_name>
    <phone>650 646 0014</phone>
    <email>cindykin@stanford.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brice Gaudilliere</last_name>
      <phone>617-230-5927</phone>
      <email>gbrice@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>Franck Verdonk, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Martin Angst, Prof.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Julien Hedou</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gaudilliere B, Fragiadakis GK, Bruggner RV, Nicolau M, Finck R, Tingle M, Silva J, Ganio EA, Yeh CG, Maloney WJ, Huddleston JI, Goodman SB, Davis MM, Bendall SC, Fantl WJ, Angst MS, Nolan GP. Clinical recovery from surgery correlates with single-cell immune signatures. Sci Transl Med. 2014 Sep 24;6(255):255ra131. doi: 10.1126/scitranslmed.3009701.</citation>
    <PMID>25253674</PMID>
  </reference>
  <reference>
    <citation>Aghaeepour N, Kin C, Ganio EA, Jensen KP, Gaudilliere DK, Tingle M, Tsai A, Lancero HL, Choisy B, McNeil LS, Okada R, Shelton AA, Nolan GP, Angst MS, Gaudilliere BL. Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery. J Immunol. 2017 Aug 9:ji1700421. doi: 10.4049/jimmunol.1700421. Online ahead of print.</citation>
    <PMID>28794234</PMID>
  </reference>
  <reference>
    <citation>Fragiadakis GK, Gaudilliere B, Ganio EA, Aghaeepour N, Tingle M, Nolan GP, Angst MS. Patient-specific Immune States before Surgery Are Strong Correlates of Surgical Recovery. Anesthesiology. 2015 Dec;123(6):1241-55. doi: 10.1097/ALN.0000000000000887.</citation>
    <PMID>26655308</PMID>
  </reference>
  <reference>
    <citation>Barberan-Garcia A, Ubre M, Roca J, Lacy AM, Burgos F, Risco R, Momblan D, Balust J, Blanco I, Martinez-Palli G. Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial. Ann Surg. 2018 Jan;267(1):50-56. doi: 10.1097/SLA.0000000000002293.</citation>
    <PMID>28489682</PMID>
  </reference>
  <reference>
    <citation>Minnella EM, Awasthi R, Loiselle SE, Agnihotram RV, Ferri LE, Carli F. Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial. JAMA Surg. 2018 Dec 1;153(12):1081-1089. doi: 10.1001/jamasurg.2018.1645.</citation>
    <PMID>30193337</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>April 14, 2023</last_update_submitted>
  <last_update_submitted_qc>April 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Brice Gaudilliere</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Personalized program</keyword>
  <keyword>Physical Activity</keyword>
  <keyword>Stress-reduction</keyword>
  <keyword>Cognition</keyword>
  <keyword>Nutrition</keyword>
  <keyword>inflammatory</keyword>
  <keyword>immune response</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</mesh_term>
    <mesh_term>Thoracic Diseases</mesh_term>
    <mesh_term>Genital Diseases, Female</mesh_term>
    <mesh_term>Urologic 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/NCT04498208
org study id: IRB-57570
nct id: NCT04498208
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Over 30 million surgeries are performed annually in the US. Up to 30% of surgical patients
      experience delayed surgical recovery, marked by prolonged post-surgical pain, opioid
      consumption, and functional impairment, which contributes $8 billion annually to US health
      care costs. Novel interventions that improve the resolution of pain, minimize opioid
      exposure, and accelerate functional recovery after surgery are urgently needed.

      Multi-modal pre-operative optimization programs (or "prehab") integrating exercise,
      nutrition, and stress reduction have been shown to safely and effectively improve outcomes
      after surgery. However, no objective biological markers assess prehab effectiveness and are
      able to tailor prehab programs to individual patients. Surgery is a profound immunological
      perturbation, during which a complex network of innate and adaptive immune cells is mobilized
      to organize the recovery process of wound healing, tissue repair, and pain resolution. As
      such, the in-depth assessment of a patient's immune system before surgery is a promising
      approach to tailor prehab programs to modifiable biological markers associated with surgical
      recovery. The primary goal of this clinical trial is to determine the effect of a
      personalized prehab program on patients immunological status before surgery.
The study design is a prospective monocenter single-blinded randomized controlled trial in
      patients undergoing elective major abdominal surgery.

        -  Patients will be recruited during the surgical consultation, at least 14 days prior to
           surgery. If they choose to enroll, they will undergo randomization on the day of
           enrollment.

        -  Prehabilitation (Day 0): personalized or standard prehabilitation program will be
           proposed to the patients for a period of 2 to 6 weeks. Immunological, nutritional,
           physical, cognitive, anxiety and quality of life status will be quantified at baseline
           by previously trained personnel.

        -  From the beginning (Day 0) to the end of the prehabilitation program (Day 14 to Day 42):
           every 7 days, a compliance questionnaire will be filled by phone, by a trained member of
           the research team blinded to the treatment arm of the study

        -  End of the prehabilitation period (Day 14 to Day 42): Immunological, nutritional,
           physical, cognitive and anxiety status after prehabilitation will be recorded by a
           trained member of the research team blinded to the treatment arm of the study.

        -  Surgery (Day S)

        -  Post operative period

             -  From Day S (2 hours after surgery end) to discharge from the hospital, length of
                stay, pain and adverse clinical events will be measured and recorded.

             -  Immunological status will be assessed at Day S+1 by blood draw.

             -  Cognitive function, neuropathic pain and quality of life will be assessed at Day S
                + 30.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
measure: Composite immunological score
time frame: immediately preoperatively
description: Composite immunological score containing a combination of blood immune cell frequencies and intracellular signaling responses. This score will be normalized to "baseline" (i.e. before prehabilitation) score for each patient.
measure: Proportion of compliant patients
time frame: immediately preoperatively
description: Patient's compliance to prehabilitation programs will be evaluated using a modified Rehabilitation Adherence Measure scale, that will be filled by phone every 7 days during the prehabilitation program, i.e. 2 to 6 times by patient. Compliant patient will be defined by a mean score >= 8/10.
measure: 6 Min Walk Test
time frame: immediately preoperatively
description: Changes in physical status will be examined using 6 Min Walk Test. The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Timed Up and Go Test
time frame: immediately preoperatively
description: Changes in physical status will be examined using Timed Up and Go Test. The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Five Times Sit to Stand Test
time frame: immediately preoperatively
description: Changes in physical status will be examined using Five Times Sit to Stand Test. The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Wall Squat Test
time frame: immediately preoperatively
description: Changes in physical status will be examined using Wall Squat Test. The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Body Mass Index
time frame: immediately preoperatively
description: Body Mass Index will be recorded. The evaluation should be based on differences between pre- and post prehabilitation performance
measure: Amsterdam Preoperative Anxiety and Information Scale
time frame: immediately preoperatively
description: Prevalence and global severity of anxiety will be evaluated using the APAIS (Amsterdam Preoperative Anxiety and Information Scale). The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Pain Catastrophizing Scale
time frame: immediately preoperatively
description: Prevalence and global severity of anxiety will be evaluated using the Pain Catastrophizing Scale. The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Changes in diet
time frame: immediately preoperatively
description: Mediterranean Diet Score will be collected. The evaluation should be based on differences between pre- and post prehabilitation performance. A high intake of Mediterranean foods: cereals, legumes, fruit, vegetables, fish, Mon-unsaturated fatty acids to Saturated fatty acids (M/S) ratio, and wine were scored positive (1) and a high intake of the non-Mediterranean foods: dairy and meat negative (0). The score ranged from 0 to 9 and the higher the score the better the compliance to a traditional Mediterranean diet.
measure: Changes in cognitive functions
time frame: immediately preoperatively
description: Cognitive functions will evaluated by the qMCI test. The evaluation should be based on differences between pre- and post prehabilitation performance.
measure: Incidence of postoperative complications
time frame: Postoperatively through to 30 days after surgery
description: Postoperative complications will be scored by the Comprehensive Complication Index. The Comprehensive Complication Index (CCI®) is based on the complication grading by Clavien-Dindo Classification and implements every occurred complication after an intervention. The overall morbidity is reflected on a scale from 0 (no complication) to 100 (death).
measure: Postoperative pain
time frame: Postoperatively through to 7 days after surgery
description: Pain scores will be assessed daily by the patient-reported Visual Analog Scale. Visual analog scale to assess the perceived stress on a horizontal, non-calibrated line of 10 cm, ranging from very low (0) to very high (10)
measure: Cumulative opioid consumption
time frame: Postoperatively through to day 7
description: Cumulative opioid consumption will be obtained from the patients' charts up to 7 days after surgery or discharge from hospital if earlier.
measure: Neuropathic pain
time frame: 30 days after surgery
description: Neuropathic pain will be measured by the Patient Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality scale (PROMIS-PQ-Neuro). The questionnaire contains 5 items questions. Scores are based on patient responses to questions about pain intensity. 0 indicates no pain; 5 indicates the most pain imaginable. The total score may be up to 25.
measure: Hospital length of stay
time frame: 30 days after surgery
description: Hospital length of stay assessed from patients' medical administrative data in days
measure: Changes in quality of life
time frame: 30 days after surgery
description: Quality of life evaluated thanks to the SF-36 scale is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. Results will be normalized on "baseline" (before prehab) scores.
arm group label: Personalized prehabilitation
arm group type: Experimental
description: Patients will participate in a personalized health optimization program combining one-on-one coaching, tailored to each patient's physical, nutritional, well-being and cognitive status baseline. Prehabilitation will last from a minimum of 14 days to a maximum of 42 days before surgery
arm group label: Standard prehabilitation
arm group type: No Intervention
description: Patients in the control group will be provided with standard instructions in a hard-copy form specific to prehabilitation before surgery associating physical, nutritional, stress-reduction and cognitive recommendations without any personalized coaching for at least 14 days prior to surgery.
intervention type: Behavioral
intervention name: Physical Prehabilitation
description: First, an evaluation of patient's aerobic capacity, functional mobility, functional strength, ambulation, fall risk, and overall mobility will be done by a trained member of the research team. Based on their functional level and preexisting conditions, therapeutic exercises will be recommended to optimize their strength, endurance, flexibility, and functional mobility in preparation for surgery. Decisions about the interventions are based on the assessment, individual patient characteristics, environmental factors, surgical type, and monitoring of the client's response and progress. Weekly sessions are 30-45 minutes long to monitor the client's response and progress their program. Based on their response to exercise (evaluated also by 2 apps: Timed Walk App and Smart Metronome & Tuner App), re-evaluation via the assessments described above, change their plan of care (alter frequency, resistance, exercises) or discontinuation of treatment could be decided.
arm group label: Personalized prehabilitation
intervention type: Behavioral
intervention name: Stress Reduction Prehabilitation
description: Participants will have the opportunity to learn techniques for mindfulness that have been established to reduce stress and assist with pain management with a member of the research team. Patients will be offered to listen to audio recording of relaxation sessions. Each session contains a relaxation technique that the patient practices while listening to the recording. Then the technique is used the next as a baseline to introduce a new technique more advanced. For some patients who struggle with the techniques the program will be adapted. Patients will choose 2 or 3 techniques and work on them.
arm group label: Personalized prehabilitation
intervention type: Behavioral
intervention name: Cognitive Prehabilitation
description: Cognitive prehabilitation will consist on the daily use of Lumosity training program, an already existing free app built to increase memory skills. The program proposed by Lumosity is tailored to each patient. The use of Lumosity will be monitored at each in-person session. Patients will be expected to complete at least three 5-minute sessions of Lumosity training per day.
arm group label: Personalized prehabilitation
intervention type: Behavioral
intervention name: Nutrition Prehabilitation
description: Nutrition prehabilitation will involve transitioning the patient to the Mediterranean diet with targets regarding hydration and the proportion of fruits, vegetables, whole grains, and healthy fats the patient will consume in a given day. This nutritional program is flexible, and it allows for specific physician and nutritionist-recommended dietary needs to be incorporated. The patient is also given tools to encourage success in healthier eating, including recipes, sample menus, healthy restaurant options, meal kit options, and local CSA box options
arm group label: Personalized prehabilitation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brice Gaudilliere, MD, PhD
role: Principal Investigator
affiliation: Stanford University
last name: Cindy Kin, MD, MS
role: Principal Investigator
affiliation: Stanford University
last name: Brice Gaudilliere, MD, PhD
phone: 617 230 5927
email: gbrice@stanford.edu
last name: Cindy Kin, MD, MS
phone: 650 646 0014
email: cindykin@stanford.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United States
citation: Gaudilliere B, Fragiadakis GK, Bruggner RV, Nicolau M, Finck R, Tingle M, Silva J, Ganio EA, Yeh CG, Maloney WJ, Huddleston JI, Goodman SB, Davis MM, Bendall SC, Fantl WJ, Angst MS, Nolan GP. Clinical recovery from surgery correlates with single-cell immune signatures. Sci Transl Med. 2014 Sep 24;6(255):255ra131. doi: 10.1126/scitranslmed.3009701.
PMID: 25253674
citation: Aghaeepour N, Kin C, Ganio EA, Jensen KP, Gaudilliere DK, Tingle M, Tsai A, Lancero HL, Choisy B, McNeil LS, Okada R, Shelton AA, Nolan GP, Angst MS, Gaudilliere BL. Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery. J Immunol. 2017 Aug 9:ji1700421. doi: 10.4049/jimmunol.1700421. Online ahead of print.
PMID: 28794234
citation: Fragiadakis GK, Gaudilliere B, Ganio EA, Aghaeepour N, Tingle M, Nolan GP, Angst MS. Patient-specific Immune States before Surgery Are Strong Correlates of Surgical Recovery. Anesthesiology. 2015 Dec;123(6):1241-55. doi: 10.1097/ALN.0000000000000887.
PMID: 26655308
citation: Barberan-Garcia A, Ubre M, Roca J, Lacy AM, Burgos F, Risco R, Momblan D, Balust J, Blanco I, Martinez-Palli G. Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial. Ann Surg. 2018 Jan;267(1):50-56. doi: 10.1097/SLA.0000000000002293.
PMID: 28489682
citation: Minnella EM, Awasthi R, Loiselle SE, Agnihotram RV, Ferri LE, Carli F. Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial. JAMA Surg. 2018 Dec 1;153(12):1081-1089. doi: 10.1001/jamasurg.2018.1645.
PMID: 30193337
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Brice Gaudilliere
investigator title: Principal Investigator
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
mesh term: Thoracic Diseases
mesh term: Genital Diseases, Female
mesh term: Urologic Diseases
sharing ipd: No