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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

January 30, 2012
December 16, 2013
July 2011
June 2013   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01523353 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 sesions [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Serious adverse events within exercise program [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    We 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.
Not Provided
Not Provided
 
Prehabilitation in Liver Surgery
Feasibility Study of Preoperative Exercise Intervention in the Resection of Colorectal Liver Metastasis.

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
  • Colorectal Cancer
  • Colorectal Liver Metastasis
  • Liver Surgery
  • Exercise Intervention
Behavioral: Exercise Intervention
4 week personalised exercise program on a static cycle. Supervised in a hospital environment
  • Active Comparator: Exercise Intervention
    4 week personalised exercise program on a static bicycle.
    Intervention: Behavioral: Exercise Intervention
  • No Intervention: Control Arm
    Patients having standard preoperative preparation and advice.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
37
June 2013
June 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01523353
11/H1005/3
No
Declan Dunne, Aintree University Hospitals NHS Foundation Trust
Aintree University Hospitals NHS Foundation Trust
Not Provided
Principal Investigator: Declan FJ Dunne, MBChB(Hons) Aintree University Hospitals NHS Foundation Trust
Aintree University Hospitals NHS Foundation Trust
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP