Prehabilitation to Improve Heart Rate Variability (PRIME)

NCT06744413 | Recruiting DMC

• 1 other identifier: PNRR-MCNT2-2023-12377934
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 4

Brief Summary

Cancer patients require chronic management and care. For those individuals living with cancer, a comprehensive approach that acknowledges the interdisciplinary nature of their condition can help guide appropriate care strategies and support their overall well-being. Approximately 45% of patients diagnosed with cancer undergo surgery to remove their tumor. Despite the advancements in surgical techniques, anesthesia, and perioperative care, major cancer surgeries still pose a significant challenge leading to a considerable decline in physiological and functional capacity. Traditionally, efforts focused on postoperative rehabilitation to enhance recovery. Recently, prehabilitation, a form of rehabilitation which aims to improve functional capacity before surgery, has gained attention for its potential benefits in improving surgical outcomes. However, prehabilitation lacks objective assessment measures to evaluate its effectiveness. Developing validated outcome measures is essential to enhance the impact of prehabilitation on surgical outcomes and long-term care for cancer patients. Heart rate variability (HRV) is a physiological parameter that measures the variation in time intervals between consecutive heartbeats, reflecting the autonomic nervous system activity which might serve as a valuable solution for objective outcome measures in evaluating the effectiveness of prehabilitation for cancer patients, providing an objective tool to assess and monitor physiological response to stress, recovery capacity, and autonomic nervous system activity. A multicenter randomized controlled trial will be conducted to assess the impact of a multimodal prehabilitation program on HRV. Patients aged 18 or older, scheduled for elective major cancer surgery will be randomized to receive either prehabilitation or standard care. The prehabilitation arm will receive a program involving home-based physical, nutritional, and psychological interventions for at least four weeks. Participants allocated to the control group will receive usual care. Patients will be followed throughout the study using an innovative mobile application, allowing for real-time monitoring and data collection during the prehabilitation program. The study has two primary outcomes: A) to assess the impact of prehabilitation on increasing preoperative HRV in chronic cancer patients undergoing surgery; B) to assess the effect of prehabilitation on length of hospital stay.

Conditions

Cancer Surgery

Keywords

Cancer surgery; Prehabilitation; Multimodal prehabilitation program; Standard care treatment; Hospital stay; Functional walking; Nutrition; Diet; Exercise; Relaxation; Functional recovery; Anesthesiology

Outcome Measures

Primary Outcomes (2)

• Assess the impact of prehabilitation on heart rate variability

  This primary outcome measure will be the change in the standard deviation of normal-to-normal intervals (SDNN) from baseline to the day before surgery.

  Preoperative

• Days at home within first 30 days after surgery

  The mean number of days at home in the first 30 days after surgery will be compared between groups

  30-days after surgery

Secondary Outcomes (5)

• Quality of life at 30 days

  30-days after surgery

• 30-days postoperative complication

  30-days after surgery

• Correlation between preoperative standard deviation of all normal to normal R-R intervals (SDNN) and quality of life at 30 days postoperatively

  30-days after surgery

• Correlation between preoperative SDNN and DAH-30

  30-days after surgery

• Correlation between preoperative SDNN and postoperative complication

  30-days after surgery

Study Arms (2)

Prehabilitation

EXPERIMENTAL

Prehabilitation arm groups will receive preoperative intervention which includes exercise training, nutritional therapy and anxiety reducing techniques, aimed at preventing or attenuating surgery-driven functional decline.

Behavioral: Multimodal prehabilitation program

Control group

NO INTERVENTION

Standard care treatment: application of ERAS pathways (Enhanced Recovery After Surgery)

Interventions

Multimodal prehabilitation program BEHAVIORAL

A tailored intervention will be prescribed if specific physical, nutritional or psychological impairments will be identified during the assessment phase. Based on the data obtained during the multimodal assessment, different domains and levels of care will be prescribed, focusing on exercise training, and/or nutrition optimization, and/or distress-coping techniques. Different combinations of these three domains will be utilized to maximize their synergistic anabolic effect. The duration of the program will be set at 4 weeks.

Prehabilitation

Eligibility Criteria

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

You may qualify if:

• Scheduled to undergo elective major abdominal or thoracic cancer surgery;
• Scheduled to undergo surgery at least three weeks after enrollment;
• Age ≥ 18 years;
• Provide written informed consent;
• Willing and able to use smartphone application.

You may not qualify if:

• Presenting with very poor functional capacity;
• American Society of Anesthesiologists (ASA) physical status classes 5-6;
• Disabling orthopedic, neuromuscular, and psychiatric diseases or other conditions that preclude participation in a prehabilitation program.

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead
• Dott. Fabio Guarracino: collaborator
• Prof. Gilda Cinnella: collaborator
• Dott. Filippo Sanfilippo: collaborator

Study Sites (4)

Azienda Ospedaliero Universitaria Policlinico San Marco di Catania

Catania, 95100, Italy

ACTIVE NOT RECRUITING

Università di Foggia

Foggia, 71100, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

RECRUITING

Related Publications (32)

• The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. Am J Epidemiol. 1989 Apr;129(4):687-702.

  PMID: 2646917 BACKGROUND

• Zhou X, Ma Z, Zhang L, Zhou S, Wang J, Wang B, Fu W. Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis. J Psychosom Res. 2016 Oct;89:20-5. doi: 10.1016/j.jpsychores.2016.08.004. Epub 2016 Aug 8.

  PMID: 27663106 BACKGROUND

• Thompson PD, Arena R, Riebe D, Pescatello LS; American College of Sports Medicine. ACSM's new preparticipation health screening recommendations from ACSM's guidelines for exercise testing and prescription, ninth edition. Curr Sports Med Rep. 2013 Jul-Aug;12(4):215-7. doi: 10.1249/JSR.0b013e31829a68cf. No abstract available.

  PMID: 23851406 BACKGROUND

• Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

  PMID: 8598068 BACKGROUND

• Tarvainen MP, Niskanen JP, Lipponen JA, Ranta-Aho PO, Karjalainen PA. Kubios HRV--heart rate variability analysis software. Comput Methods Programs Biomed. 2014;113(1):210-20. doi: 10.1016/j.cmpb.2013.07.024. Epub 2013 Aug 6.

  PMID: 24054542 BACKGROUND

• Scheede-Bergdahl C, Minnella EM, Carli F. Multi-modal prehabilitation: addressing the why, when, what, how, who and where next? Anaesthesia. 2019 Jan;74 Suppl 1:20-26. doi: 10.1111/anae.14505.

  PMID: 30604416 BACKGROUND

• Orange ST, Northgraves MJ, Marshall P, Madden LA, Vince RV. Exercise prehabilitation in elective intra-cavity surgery: A role within the ERAS pathway? A narrative review. Int J Surg. 2018 Aug;56:328-333. doi: 10.1016/j.ijsu.2018.04.054. Epub 2018 May 3.

  PMID: 29730070 BACKGROUND

• Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, Baig W, Flapan AD, Cowley A, Prescott RJ, Neilson JM, Fox KA. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation. 1998 Oct 13;98(15):1510-6. doi: 10.1161/01.cir.98.15.1510.

  PMID: 9769304 BACKGROUND

• Myles PS, Shulman MA, Heritier S, Wallace S, McIlroy DR, McCluskey S, Sillar I, Forbes A. Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia. BMJ Open. 2017 Aug 18;7(8):e015828. doi: 10.1136/bmjopen-2017-015828.

  PMID: 28821518 BACKGROUND

• Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D, Christophi C, Leslie K, McGuinness S, Parke R, Serpell J, Chan MTV, Painter T, McCluskey S, Minto G, Wallace S; Australian and New Zealand College of Anaesthetists Clinical Trials Network and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery. N Engl J Med. 2018 Jun 14;378(24):2263-2274. doi: 10.1056/NEJMoa1801601. Epub 2018 May 9.

  PMID: 29742967 BACKGROUND

• Mostarda C, Castro-Filha J, Reis AD, Sevilio M Jr, Dias CJ, Silva-Filho AC, Garcia JBS, do Desterro Nascimento M, Coelho-Junior HJ, Rodrigues B. Short-term combined exercise training improves cardiorespiratory fitness and autonomic modulation in cancer patients receiving adjuvant therapy. J Exerc Rehabil. 2017 Oct 30;13(5):599-607. doi: 10.12965/jer.1735048.524. eCollection 2017 Oct.

  PMID: 29114536 BACKGROUND

• Scott WR. Conflicting levels of rationality: regulators, managers, and professionals in the medical care sector. J Health Adm Educ. 1985 Spring;3(2 Pt 2):113-31. No abstract available.

  PMID: 10276329 BACKGROUND

• Marinelli V, Danzi OP, Mazzi MA, Secchettin E, Tuveri M, Bonamini D, Rimondini M, Salvia R, Bassi C, Del Piccolo L. PREPARE: PreoPerative Anxiety REduction. One-Year Feasibility RCT on a Brief Psychological Intervention for Pancreatic Cancer Patients Prior to Major Surgery. Front Psychol. 2020 Mar 5;11:362. doi: 10.3389/fpsyg.2020.00362. eCollection 2020.

  PMID: 32194490 BACKGROUND

• Lundstrom CJ, Foreman NA, Biltz G. Practices and Applications of Heart Rate Variability Monitoring in Endurance Athletes. Int J Sports Med. 2023 Jan;44(1):9-19. doi: 10.1055/a-1864-9726. Epub 2022 Jul 19.

  PMID: 35853460 BACKGROUND

• Leite MR, Ramos EM, Kalva-Filho CA, Rodrigues FM, Freire AP, Tacao GY, de Toledo AC, Cecilio MJ, Vanderlei LC, Ramos D. Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD. Respirology. 2015 Feb;20(2):273-8. doi: 10.1111/resp.12424. Epub 2014 Nov 9.

  PMID: 25381699 BACKGROUND

• Lavin-Perez AM, Collado-Mateo D, Mayo X, Liguori G, Humphreys L, Jimenez A. Can Exercise Reduce the Autonomic Dysfunction of Patients With Cancer and Its Survivors? A Systematic Review and Meta-Analysis. Front Psychol. 2021 Aug 24;12:712823. doi: 10.3389/fpsyg.2021.712823. eCollection 2021.

  PMID: 34504462 BACKGROUND

• Larsen AI, Gjesdal K, Hall C, Aukrust P, Aarsland T, Dickstein K. Effect of exercise training in patients with heart failure: a pilot study on autonomic balance assessed by heart rate variability. Eur J Cardiovasc Prev Rehabil. 2004 Apr;11(2):162-7. doi: 10.1097/01.hjr.0000124214.21584.bb.

  PMID: 15187821 BACKGROUND

• Landoni G, Lomivorotov VV, Alvaro G, Lobreglio R, Pisano A, Guarracino F, Calabro MG, Grigoryev EV, Likhvantsev VV, Salgado-Filho MF, Bianchi A, Pasyuga VV, Baiocchi M, Pappalardo F, Monaco F, Boboshko VA, Abubakirov MN, Amantea B, Lembo R, Brazzi L, Verniero L, Bertini P, Scandroglio AM, Bove T, Belletti A, Michienzi MG, Shukevich DL, Zabelina TS, Bellomo R, Zangrillo A; CHEETAH Study Group. Levosimendan for Hemodynamic Support after Cardiac Surgery. N Engl J Med. 2017 May 25;376(21):2021-2031. doi: 10.1056/NEJMoa1616325. Epub 2017 Mar 21.

  PMID: 28320259 BACKGROUND

• Landoni G, Lomivorotov VV, Nigro Neto C, Monaco F, Pasyuga VV, Bradic N, Lembo R, Gazivoda G, Likhvantsev VV, Lei C, Lozovskiy A, Di Tomasso N, Bukamal NAR, Silva FS, Bautin AE, Ma J, Crivellari M, Farag AMGA, Uvaliev NS, Carollo C, Pieri M, Kunstyr J, Wang CY, Belletti A, Hajjar LA, Grigoryev EV, Agro FE, Riha H, El-Tahan MR, Scandroglio AM, Elnakera AM, Baiocchi M, Navalesi P, Shmyrev VA, Severi L, Hegazy MA, Crescenzi G, Ponomarev DN, Brazzi L, Arnoni R, Tarasov DG, Jovic M, Calabro MG, Bove T, Bellomo R, Zangrillo A; MYRIAD Study Group. Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery. N Engl J Med. 2019 Mar 28;380(13):1214-1225. doi: 10.1056/NEJMoa1816476. Epub 2019 Mar 19.

  PMID: 30888743 BACKGROUND

• Lambert JE, Hayes LD, Keegan TJ, Subar DA, Gaffney CJ. The Impact of Prehabilitation on Patient Outcomes in Hepatobiliary, Colorectal, and Upper Gastrointestinal Cancer Surgery: A PRISMA-Accordant Meta-analysis. Ann Surg. 2021 Jul 1;274(1):70-77. doi: 10.1097/SLA.0000000000004527.

  PMID: 33201129 BACKGROUND

• Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987 Feb 1;59(4):256-62. doi: 10.1016/0002-9149(87)90795-8.

  PMID: 3812275 BACKGROUND

• Kemp AH, Quintana DS. The relationship between mental and physical health: insights from the study of heart rate variability. Int J Psychophysiol. 2013 Sep;89(3):288-96. doi: 10.1016/j.ijpsycho.2013.06.018. Epub 2013 Jun 22.

  PMID: 23797149 BACKGROUND

• Kaikkonen KM, Korpelainen RI, Tulppo MP, Kaikkonen HS, Vanhala ML, Kallio MA, Keinanen-Kiukaanniemi SM, Korpelainen JT. Physical activity and aerobic fitness are positively associated with heart rate variability in obese adults. J Phys Act Health. 2014 Nov;11(8):1614-21. doi: 10.1123/jpah.2012-0405. Epub 2014 Feb 5.

  PMID: 24508687 BACKGROUND

• Jarczok MN, Weimer K, Braun C, Williams DP, Thayer JF, Gundel HO, Balint EM. Heart rate variability in the prediction of mortality: A systematic review and meta-analysis of healthy and patient populations. Neurosci Biobehav Rev. 2022 Dec;143:104907. doi: 10.1016/j.neubiorev.2022.104907. Epub 2022 Oct 13.

  PMID: 36243195 BACKGROUND

• Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, Cobb FR, Pryor DB. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am J Cardiol. 1989 Sep 15;64(10):651-4. doi: 10.1016/0002-9149(89)90496-7.

  PMID: 2782256 BACKGROUND

• Fadul N, Strasser F, Palmer JL, Yusuf SW, Guo Y, Li Z, Allo J, Bruera E. The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report. J Pain Symptom Manage. 2010 Feb;39(2):283-90. doi: 10.1016/j.jpainsymman.2009.06.014.

  PMID: 20152590 BACKGROUND

• Durrand J, Singh SJ, Danjoux G. Prehabilitation. Clin Med (Lond). 2019 Nov;19(6):458-464. doi: 10.7861/clinmed.2019-0257.

  PMID: 31732585 BACKGROUND

• Dekker JM, Crow RS, Folsom AR, Hannan PJ, Liao D, Swenne CA, Schouten EG. Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities. Circulation. 2000 Sep 12;102(11):1239-44. doi: 10.1161/01.cir.102.11.1239.

  PMID: 10982537 BACKGROUND

• De Couck M, van Brummelen D, Schallier D, De Greve J, Gidron Y. The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients. Oncol Rep. 2013 Nov;30(5):2435-41. doi: 10.3892/or.2013.2725. Epub 2013 Sep 9.

  PMID: 24026706 BACKGROUND

• Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96. doi: 10.1097/SLA.0b013e3181b13ca2.

  PMID: 19638912 BACKGROUND

• Brooks R. EuroQol: the current state of play. Health Policy. 1996 Jul;37(1):53-72. doi: 10.1016/0168-8510(96)00822-6.

  PMID: 10158943 BACKGROUND

• Bell M, Eriksson LI, Svensson T, Hallqvist L, Granath F, Reilly J, Myles PS. Days at Home after Surgery: An Integrated and Efficient Outcome Measure for Clinical Trials and Quality Assurance. EClinicalMedicine. 2019 Apr 27;11:18-26. doi: 10.1016/j.eclinm.2019.04.011. eCollection 2019 May-Jun.

  PMID: 31317130 BACKGROUND

MeSH Terms

Conditions

Motor Activity

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Fabio Guarracino, Doctor

  Azienda Ospedaliero, Universitaria Pisana

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabio Guarracino, Dr

CONTACT

+393281652528; f.guarracino@ao-pisa.toscana.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 20, 2024
• Study Start: December 20, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)