Immune Modulation by Enhanced vs Standard Prehabilitation Program Before Major Surgery

NCT04498208 | Completed

• 1 other identifier: IRB-57570
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  immediately preoperatively

Secondary Outcomes (16)

• Proportion of compliant patients

  immediately preoperatively

• 6 Min Walk Test

  immediately preoperatively

• Timed Up and Go Test

  immediately preoperatively

• Five Times Sit to Stand Test

  immediately preoperatively

• Wall Squat Test

  immediately preoperatively

Study Arms (2)

Personalized prehabilitation

EXPERIMENTAL

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; Behavioral: Stress Reduction Prehabilitation; Behavioral: Cognitive Prehabilitation; Behavioral: Nutrition Prehabilitation

Standard prehabilitation

NO INTERVENTION

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.

Interventions

Physical Prehabilitation BEHAVIORAL

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.

Personalized prehabilitation

Stress Reduction Prehabilitation BEHAVIORAL

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.

Personalized prehabilitation

Cognitive Prehabilitation BEHAVIORAL

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.

Personalized prehabilitation

Nutrition Prehabilitation BEHAVIORAL

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

Personalized prehabilitation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (7)

• 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 BACKGROUND

• 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.

  PMID: 28794234 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Cambriel A, Tsai A, Choisy B, Sabayev M, Hedou J, Shelton E, Singh K, Amar J, Badea V, Bruckman S, Ganio E, Einhaus J, Feyaerts D, Stelzer I, Sato M, Langeron O, Bonham TA, Gaudilliere D, Shelton A, Kin C, Gaudilliere B, Verdonk F. Immune Modulation by Personalized vs Standard Prehabilitation Before Major Surgery: A Randomized Clinical Trial. JAMA Surg. 2026 Jan 1;161(1):20-30. doi: 10.1001/jamasurg.2025.4917.

  PMID: 41222945 DERIVED

• Cambriel A, Tsai A, Choisy B, Sabayev M, Hedou J, Shelton E, Singh K, Amar J, Badea V, Bruckman S, Ganio E, Einhaus J, Feyaerts D, Stelzer I, Sato M, Langeron O, Bonham TA, Gaudilliere D, Shelton A, Kin C, Gaudilliere B, Verdonk F. Immune Modulation by Personalized vs. Standard Prehabilitation Before Major Surgery: A Randomized Controlled Trial. medRxiv [Preprint]. 2025 Jun 4:2025.06.03.25328894. doi: 10.1101/2025.06.03.25328894.

  PMID: 40502574 DERIVED

MeSH Terms

Conditions

Gastrointestinal Diseases; Urologic Diseases; Genital Diseases, Female; Thoracic Diseases; Motor Activity

Condition Hierarchy (Ancestors)

Digestive System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Respiratory Tract Diseases; Behavior

Study Officials

• Brice Gaudilliere, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Cindy Kin, MD, MS

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: August 4, 2020
• Study Start: October 7, 2020
• Primary Completion: April 21, 2024
• Study Completion: April 21, 2024
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)