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Immune Modulation by Enhanced vs Standard Prehabilitation Program Before Major Surgery

Primary Purpose

Surgery, Immune System and Related Disorders, Preoperative Care

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Physical Prehabilitation
Stress Reduction Prehabilitation
Cognitive Prehabilitation
Nutrition Prehabilitation
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Surgery focused on measuring Personalized program, Physical Activity, Stress-reduction, Cognition, Nutrition, inflammatory, immune response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Personalized prehabilitation

Standard prehabilitation

Arm 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

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.

Outcomes

Primary Outcome Measures

Composite immunological score
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

Proportion of compliant patients
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.
6 Min Walk Test
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.
Timed Up and Go Test
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.
Five Times Sit to Stand Test
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.
Wall Squat Test
Changes in physical status will be examined using Wall Squat Test. The evaluation should be based on differences between pre- and post prehabilitation performance.
Body Mass Index
Body Mass Index will be recorded. The evaluation should be based on differences between pre- and post prehabilitation performance
Amsterdam Preoperative Anxiety and Information Scale
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.
Pain Catastrophizing Scale
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.
Changes in diet
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.
Changes in cognitive functions
Cognitive functions will evaluated by the qMCI test. The evaluation should be based on differences between pre- and post prehabilitation performance.
Incidence of postoperative complications
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).
Postoperative pain
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)
Cumulative opioid consumption
Cumulative opioid consumption will be obtained from the patients' charts up to 7 days after surgery or discharge from hospital if earlier.
Neuropathic pain
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.
Hospital length of stay
Hospital length of stay assessed from patients' medical administrative data in days
Changes in quality of life
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.

Full Information

First Posted
July 28, 2020
Last Updated
October 9, 2023
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT04498208
Brief Title
Immune Modulation by Enhanced vs Standard Prehabilitation Program Before Major Surgery
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 7, 2020 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgery, Immune System and Related Disorders, Preoperative Care, Gastrointestinal Disease, Urological Disease, Gynecologic Disease, Thoracic Diseases
Keywords
Personalized program, Physical Activity, Stress-reduction, Cognition, Nutrition, inflammatory, immune response

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Care ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Personalized prehabilitation
Arm Type
Experimental
Arm 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 Title
Standard prehabilitation
Arm Type
No Intervention
Arm 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(s)
Physical Prehabilitation
Intervention 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.
Intervention Type
Behavioral
Intervention Name(s)
Stress Reduction Prehabilitation
Intervention 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.
Intervention Type
Behavioral
Intervention Name(s)
Cognitive Prehabilitation
Intervention 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.
Intervention Type
Behavioral
Intervention Name(s)
Nutrition Prehabilitation
Intervention 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
Primary Outcome Measure Information:
Title
Composite immunological score
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.
Time Frame
immediately preoperatively
Secondary Outcome Measure Information:
Title
Proportion of compliant patients
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.
Time Frame
immediately preoperatively
Title
6 Min Walk Test
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.
Time Frame
immediately preoperatively
Title
Timed Up and Go Test
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.
Time Frame
immediately preoperatively
Title
Five Times Sit to Stand Test
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.
Time Frame
immediately preoperatively
Title
Wall Squat Test
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.
Time Frame
immediately preoperatively
Title
Body Mass Index
Description
Body Mass Index will be recorded. The evaluation should be based on differences between pre- and post prehabilitation performance
Time Frame
immediately preoperatively
Title
Amsterdam Preoperative Anxiety and Information Scale
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.
Time Frame
immediately preoperatively
Title
Pain Catastrophizing Scale
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.
Time Frame
immediately preoperatively
Title
Changes in diet
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.
Time Frame
immediately preoperatively
Title
Changes in cognitive functions
Description
Cognitive functions will evaluated by the qMCI test. The evaluation should be based on differences between pre- and post prehabilitation performance.
Time Frame
immediately preoperatively
Title
Incidence of postoperative complications
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).
Time Frame
Postoperatively through to 30 days after surgery
Title
Postoperative pain
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)
Time Frame
Postoperatively through to 7 days after surgery
Title
Cumulative opioid consumption
Description
Cumulative opioid consumption will be obtained from the patients' charts up to 7 days after surgery or discharge from hospital if earlier.
Time Frame
Postoperatively through to day 7
Title
Neuropathic pain
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.
Time Frame
30 days after surgery
Title
Hospital length of stay
Description
Hospital length of stay assessed from patients' medical administrative data in days
Time Frame
30 days after surgery
Title
Changes in quality of life
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.
Time Frame
30 days after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brice Gaudilliere, MD, PhD
Phone
617 230 5927
Email
gbrice@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Cindy Kin, MD, MS
Phone
650 646 0014
Email
cindykin@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brice Gaudilliere, MD, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cindy Kin, MD, MS
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brice Gaudilliere
Phone
617-230-5927
Email
gbrice@stanford.edu
First Name & Middle Initial & Last Name & Degree
Franck Verdonk, MD, PhD
First Name & Middle Initial & Last Name & Degree
Martin Angst, Prof.
First Name & Middle Initial & Last Name & Degree
Julien Hedou

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25253674
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.
Results Reference
background
PubMed Identifier
28794234
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.
Results Reference
background
PubMed Identifier
26655308
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.
Results Reference
background
PubMed Identifier
28489682
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.
Results Reference
background
PubMed Identifier
30193337
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.
Results Reference
background

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Immune Modulation by Enhanced vs Standard Prehabilitation Program Before Major Surgery

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