Prehabilitation in Liver Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Declan Dunne, Aintree University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01523353
First received: January 30, 2012
Last updated: December 16, 2013
Last verified: February 2012
  Purpose

Each year in the UK around 1500 patients undergo surgery for bowel cancer that has spread to the liver. This is major surgery that offers a chance of cure, but can be associated with complications. Fitter patients are less likely to have serious complications. We are interested in finding out whether a short exercise program can improve patient fitness before surgery and whether this can reduce surgical complications.

We plan to measure the fitness of patients who are going to have liver surgery. We will then give them an exercise programme for 4 weeks, after which we will assess their fitness again.

We are also interested in whether fitter people have better Liver function. To assess this we will take a small sample of liver tissue during the operation for laboratory analysis of its function.

Hypothesis

  1. A short period of exercise can significantly improve fitness prior to liver surgery
  2. Greater Fitness is associated with better liver function.

Condition Intervention Phase
Colorectal Cancer
Colorectal Liver Metastasis
Liver Surgery
Exercise Intervention
Behavioral: Exercise Intervention
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Feasibility Study of Preoperative Exercise Intervention in the Resection of Colorectal Liver Metastasis.

Resource links provided by NLM:


Further study details as provided by Aintree University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Anaerobic threshold prior to liver resection [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    This is a measure of cardiopulmonary fitness as detected by a cardiopulmonary exercise test.


Secondary Outcome Measures:
  • Hospital Length of stay [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    length of hospital admission from date of surgery

  • Post operative morbidity [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    As measured using Clavien classification and postoperative morbidity scores

  • Quality of Life [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    SF -36 and EORTC questionaires at 5 weeks, 6 weeks postoperatively, and 3 months postoperatively

  • Mortality [ Time Frame: 30 day and 90 day postoperative ] [ Designated as safety issue: Yes ]
  • Attendance at exercise sessions [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Serious adverse events within exercise program [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    The investigators are not expecting and serious adverse events during the program.

  • other measures of cardiopulmonary function [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Detected by cardiopulmonary exercise prior to surgery.

  • Recovery of fitness [ Time Frame: 6 and 12 weeks post operatively ] [ Designated as safety issue: No ]
    recovery of cardiopulmonary exercise test determined fitness post surgery.


Enrollment: 37
Study Start Date: July 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Exercise Intervention
4 week personalised exercise program on a static bicycle.
Behavioral: Exercise Intervention
4 week personalised exercise program on a static cycle. Supervised in a hospital environment
No Intervention: Control Arm
Patients having standard preoperative preparation and advice.

  Hide Detailed Description

Detailed Description:

Prehabilitation in Liver Surgery

Introduction Thirty per cent of patients with colorectal cancer have metastatic disease at time of presentation, and a further 20% will develop liver metastases after the primary colorectal malignancy has been resected. Liver resection offers the prospect of cure for a proportion of these patients and, with the increasing use of effective neo-adjuvant chemotherapy, this proportion is increasing. However, liver surgery is associated with significant morbidity and mortality and this may be higher in patients with comorbidity, poor cardiorespiratory fitness and in those who have received neo-adjuvant chemotherapy.

Cardiopulmonary exercise testing (CPET) is a non-invasive assessment of cardiovascular and pulmonary function, which can be quantified by measures such as anaerobic threshold (AT) and VO2peak. The anaerobic threshold is a measure of sustainable exercise, where the VO2peak is a measure of maximal exercise capacity. The AT has been assessed in different surgical groups and has been shown as a useful predictor of postoperative complications and survival. Early work has demonstrated that short periods of preoperative exercise intervention can improve AT and VO2peak. However, no work has to date been undertaken in patients prior to liver surgery.

Hepatic glucose metabolism provides much of the energy requirements of the postoperative period. Work has demonstrated that exercise training increases hepatic glucose production, and that its inhibition has a marked effect on endurance capability. This may be particularly relevant when surgical resections can involve resection of up to 80% of hepatic tissue. However, a link between hepatic gluconeogenic capacity and fitness as assessed by cardiopulmonary exercise testing has not been established.

A demonstrable link between gluconeogenic capacity and cardiopulmonary fitness and an explanation of its underpinning physiology would help explain some of the systemic effects of drug hepatotoxicity. It would also allow development of strategies to improve gluconeogenic capacity that may reduce complications and improve tolerance of many hepatoxic agents such as chemotherapy.

Hypothesis

  1. A short exercise program can significantly improve the CPET defined anaerobic threshold prior to liver surgery in a cancer population and this will be associated with reduced post-operative morbidity and mortality.
  2. Hepatic gluconeogenic capacity will be associated with cardiopulmonary fitness.
  3. Gluconeogenic capacity will be associated with mitochondrial number and quantity of enzymes which are integral to gluconeogenesis such as PEPCK

Methods Patients with colorectal liver metastases suitable for hepatic resection will undergo a baseline CPET and then be randomised to either preoperative exercise intervention or standard care. Patients within the intervention arm will undergo a 4 week exercise program consisting of 3 interval sessions per week on a stationary bike. This will be individually tailored according to their initial exercise test. In the week prior to surgery all patients will then undergo a further CPET. At surgery liver tissue will be taken to determine hepatic gluconeogenic capacity. CPET tests will then be performed where possible in patients at 6 weeks and 3 months following surgery. Post-operative complications (Clavien classification and Postoperative morbidity score (POMS)) and 30 and 90-day mortality will be recorded. Quality of life assessments (EORTC/SF-36) will be taken at recruitment, the week prior to surgery, 6 weeks after surgery and 3 months following surgery.

Laboratory Analysis Hepatic gluconeogenic capacity will be assessed by direct analysis of fresh slices of hepatic tissue taken at the time of surgery. Slices will be taken using the Krumdiek MD6000 tissue slicer. These will be weighed an incubated in a buffer containing lactate. Glucose will be measured using the Glucose Oxidase assay, and calculated per mg wet weight of hepatic tissue. Further analysis of mitochondrial number and ATP production, and enzymatic levels will be conducted following initial results.

Statistical considerations This is a study of a continuous response variable from matched pairs of study subjects and will need 38 patients to detect a true difference 1.5ml/min/kg, with a probability 0.8 and Type I error 0.05). Anticipated recruitment period is 10 months assuming a dropout rate of 20%. Randomisation is by computerised block randomisation, and patients will be stratified by receipt of neo-adjuvant chemotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Planned resection of colorectal liver metastasis
  • Able to perform cycle based exercise program
  • Age over 18

Exclusion Criteria:

  • Unable to consent
  • Unable to perform cycle based exercise program
  • Age under 18
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01523353

Locations
United Kingdom
Aintree University Hospital
Liverpool, Merseyside, United Kingdom, L9 7AL
Sponsors and Collaborators
Aintree University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Declan FJ Dunne, MBChB(Hons) Aintree University Hospitals NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Declan Dunne, Surgical Research Fellow, Aintree University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01523353     History of Changes
Other Study ID Numbers: 11/H1005/3
Study First Received: January 30, 2012
Last Updated: December 16, 2013
Health Authority: United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by Aintree University Hospitals NHS Foundation Trust:
Prehabilitation
Exercise
Colorectal Cancer
Surgery

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases

ClinicalTrials.gov processed this record on September 18, 2014