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Immune Modulation by Enhanced vs Standard Prehabilitation Program Before Major Surgery

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ClinicalTrials.gov Identifier: NCT04498208
Recruitment Status : Recruiting
First Posted : August 4, 2020
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Brice Gaudilliere, Stanford University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Surgery Immune System and Related Disorders Preoperative Care Gastrointestinal Disease Urological Disease Gynecologic Disease Thoracic Diseases Behavioral: Physical Prehabilitation Behavioral: Stress Reduction Prehabilitation Behavioral: Cognitive Prehabilitation Behavioral: Nutrition Prehabilitation Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
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
Actual Study Start Date : October 7, 2020
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : January 1, 2022

Arm Intervention/treatment
Experimental: Personalized prehabilitation
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
Behavioral: Physical Prehabilitation
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.

Behavioral: Stress Reduction Prehabilitation
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.

Behavioral: Cognitive Prehabilitation
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.

Behavioral: Nutrition Prehabilitation
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

No Intervention: Standard prehabilitation
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.



Primary Outcome Measures :
  1. Composite immunological score [ Time Frame: immediately preoperatively ]
    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.


Secondary Outcome Measures :
  1. Proportion of compliant patients [ Time Frame: immediately preoperatively ]
    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.

  2. 6 Min Walk Test [ Time Frame: immediately preoperatively ]
    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.

  3. Timed Up and Go Test [ Time Frame: immediately preoperatively ]
    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.

  4. Five Times Sit to Stand Test [ Time Frame: immediately preoperatively ]
    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.

  5. Wall Squat Test [ Time Frame: immediately preoperatively ]
    Changes in physical status will be examined using Wall Squat Test. The evaluation should be based on differences between pre- and post prehabilitation performance.

  6. Body Mass Index [ Time Frame: immediately preoperatively ]
    Body Mass Index will be recorded. The evaluation should be based on differences between pre- and post prehabilitation performance

  7. Amsterdam Preoperative Anxiety and Information Scale [ Time Frame: immediately preoperatively ]
    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.

  8. Pain Catastrophizing Scale [ Time Frame: immediately preoperatively ]
    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.

  9. Changes in diet [ Time Frame: immediately preoperatively ]
    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.

  10. Changes in cognitive functions [ Time Frame: immediately preoperatively ]
    Cognitive functions will evaluated by the qMCI test. The evaluation should be based on differences between pre- and post prehabilitation performance.

  11. Incidence of postoperative complications [ Time Frame: Postoperatively through to 30 days after surgery ]
    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).

  12. Postoperative pain [ Time Frame: Postoperatively through to 7 days after surgery ]
    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)

  13. Cumulative opioid consumption [ Time Frame: Postoperatively through to day 7 ]
    Cumulative opioid consumption will be obtained from the patients' charts up to 7 days after surgery or discharge from hospital if earlier.

  14. Neuropathic pain [ Time Frame: 30 days after surgery ]
    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.

  15. Hospital length of stay [ Time Frame: 30 days after surgery ]
    Hospital length of stay assessed from patients' medical administrative data in days

  16. Changes in quality of life [ Time Frame: 30 days after surgery ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients (≥ 18 years)
  • Competent to provide informed consent
  • Undergoing major elective surgery under general anesthesia in ≥14 days from enrollment (abdominal, thoracic, plastic and neurosurgeries).
  • Fluent in English

Exclusion Criteria:

  • Premorbid conditions or orthopedic impairments with contraindications to exercise
  • Cognitive disabilities defined as evolutive neurological or neurodegenerative disease
  • ASA score 4 or higher or patient under palliative care
  • Illiteracy (inability to read the English language).
  • Expected length of stay at hospital < 48 hours
  • Patient under tutorship or curatorship
  • Pregnant or breast-feeding woman
  • Absence of informed consent or request to not participate to the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04498208


Contacts
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Contact: Brice Gaudilliere, MD, PhD 617 230 5927 gbrice@stanford.edu
Contact: Cindy Kin, MD, MS 650 646 0014 cindykin@stanford.edu

Locations
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United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Brice Gaudilliere    617-230-5927    gbrice@stanford.edu   
Sub-Investigator: Franck Verdonk, MD, PhD         
Sub-Investigator: Martin Angst, Prof.         
Sub-Investigator: Julien Hedou         
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Brice Gaudilliere, MD, PhD Stanford University
Principal Investigator: Cindy Kin, MD, MS Stanford University
Publications:

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Responsible Party: Brice Gaudilliere, Principal Investigator, Stanford University
ClinicalTrials.gov Identifier: NCT04498208    
Other Study ID Numbers: IRB-57570
First Posted: August 4, 2020    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Brice Gaudilliere, Stanford University:
Personalized program
Physical Activity
Stress-reduction
Cognition
Nutrition
inflammatory
immune response
Additional relevant MeSH terms:
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Gastrointestinal Diseases
Digestive System Diseases
Thoracic Diseases
Urologic Diseases
Respiratory Tract Diseases