Clinical trial NCT04498208: 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
Overall status: COMPLETED
Phase: NA
Conditions: 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
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2020-08-04
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Composite immunological score
timeFrame: immediately preoperatively
Secondary outcomes:
measure: Proportion of compliant patients
timeFrame: immediately preoperatively
measure: 6 Min Walk Test
timeFrame: immediately preoperatively
measure: Timed Up and Go Test
timeFrame: immediately preoperatively
measure: Five Times Sit to Stand Test
timeFrame: immediately preoperatively
measure: Wall Squat Test
timeFrame: immediately preoperatively
measure: Body Mass Index
timeFrame: immediately preoperatively
measure: Amsterdam Preoperative Anxiety and Information Scale
timeFrame: immediately preoperatively
measure: Pain Catastrophizing Scale
timeFrame: immediately preoperatively
measure: Changes in diet
timeFrame: immediately preoperatively
measure: Changes in cognitive functions
timeFrame: immediately preoperatively
measure: Incidence of postoperative complications
timeFrame: Postoperatively through to 30 days after surgery
measure: Postoperative pain
timeFrame: Postoperatively through to 7 days after surgery
measure: Cumulative opioid consumption
timeFrame: Postoperatively through to day 7
measure: Neuropathic pain
timeFrame: 30 days after surgery
measure: Hospital length of stay
timeFrame: 30 days after surgery
measure: Changes in quality of life
timeFrame: 30 days after surgery
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Brice Gaudilliere, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Cindy Kin, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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: 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 Sep 15;199(6):2171-2180. doi: 10.4049/jimmunol.1700421. Epub 2017 Aug 9.
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: 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: 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.