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Body Composition Manipulation in CoLorectal cancEr (BiCyCLE): Neuromuscular Electrical Stimulation (NMES)

Not Applicable
Active, not recruiting
Conditions
Colon Cancer
Colorectal Cancer
Sarcopenic Obesity
Advanced Cancer
Recurrent Rectal Cancer
Colo-rectal Cancer
Sarcopenia
Rectal Cancer
Interventions
Device: Microstim 2v2 Stimulator
Registration Number
NCT04065984
Lead Sponsor
London North West Healthcare NHS Trust
Brief Summary

Muscle is lost as part of the rectal cancer disease process. Surgery to treat rectal cancer and its subsequent immobility leads to increased muscle loss. Neuromuscular electrical stimulation (NMES) has been shown in previous studies in the critically ill to maintain muscle mass. The investigators aim to examine whether NMES use in the pre and postoperative setting preserves muscle mass, speeds up recovery and improves outcomes in advanced rectal cancer patients undergoing curative surgery. This is a phase II double blind randomised controlled clinical trial.

Detailed Description

Myopenia (muscle wasting) occurs as part of the disease process of colorectal cancer, when coupled with the physiological demands and immobility of major surgery there is an even more profound loss in muscle mass.

Evidence suggests that patients who have greater muscle mass and better muscle quality have better post operative outcomes, fewer complications and longer survival. Patients who have pelvic surgery (complex major surgery to remove some or all the pelvic organs involved in the local spread cancer) for locally advanced rectal cancer (cancer of the last part of the large bowel) are highly immobile post operatively.

The investigators are planning to stimulate the thigh and back muscles pre and post operatively in patients undergoing surgery for locally advanced rectal cancer using a device known as a neuromuscular electrical stimulator (NMES). This device mimics exercise in patients, who are unable to exercise fully. The investigators hypothesise that this will prevent the muscle loss normally seen in advanced cancer patients and even, potentially, increase muscle bulk. The investigators will compare this patient group to a control group of patients who are having the same surgery but will use a placebo stimulation protocol. The investigators will compare short and long term outcomes, differences in inflammation and quality of life in both these patient groups.

Neuro-Muscular Electrical Stimulation has been used successfully to help provide physiotherapy in critically ill patients, in earlier studies it has shown preservation of muscle in cancer patients too.

The investigators want to identify whether NMES, as an adjunct to standard parenteral nutritional support and physiotherapy, can help maintain or even increase lean body mass and exert the anti-inflammatory effect of exercise. We want to see if using this device improves quality of life post operatively and improves patient outcomes.

The purpose of this study is to see whether muscle bulk can be preserved and muscle quality maintained in partially immobile post operative advanced rectal cancer patients. This will be done by using a neuromuscular electrical stimulator (NMES) device called a Microstim 2v2 (Odstock Medical Ltd, Salisbury, UK). The investigators are doing this because it is known from previous research that patients with more muscle and better quality muscle have better outcomes following colorectal cancer surgery. It is also known from studies in the critically ill that NMES can successfully increase muscle and can act as a surrogate for exercise. The investigators aim to identify whether muscle bulk and quality can be increased and improved in these patients and indeed, whether this reduces inflammation, improves recovery, outcomes and Quality of Life. the investigators also want to see if patients find the device easy and acceptable to use.

This will be run as a single centre double blind randomised controlled phase II trial.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
46
Inclusion Criteria
  • Adults age 18 and above
  • Male or female
  • Primary or recurrent locally advanced rectal cancer amenable to elective radical exenterative surgery
  • ASA grade I-III
  • Able and willing to consent
  • Participation in other concurrent trials is acceptable - following discussion with trial team of both studies.
Exclusion Criteria
  • Lack of patient consent
  • Wide spread metastases not amenable to curative resection
  • Contraindication to NMES (see appendix 6)
  • Pre existing neuromuscular degenerative disease
  • Participation in other trials where agreement on participation not made in advance by trial teams
  • Patients with solitary colon cancer above the level of the peritoneal reflexion which does not require complex pelvic surgery.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Neuro-Muscular electrical stimulation treatment armMicrostim 2v2 StimulatorActive muscle stimulation with a view that this will lead to muscle preservation through muscle fibre recruitment
Neuro-Muscular electrical stimulation Placebo armMicrostim 2v2 StimulatorStimulator set at a sub therapeutic threshold so as to not recruit muscle fibres
Primary Outcome Measures
NameTimeMethod
Mean muscle attenuation pre and postoperatively2 years

The difference in mean muscle attenuation (MA) measured in Hounsfield units between the pre- operative and 3 month post-operative CT scan in the NMES treatment group and the placebo NMES group.

Secondary Outcome Measures
NameTimeMethod
CT derived muscle measurements6 months

The difference in Lumbar skeletal Muscle Index (LSMI=height / area of skeletal muscle in cm2 at L3) derived from the third lumbar vertebral axial level of pre and 3 to 6 month postoperative CT scans using SliceOmatic software version 5.0 with ABACS L3 Plug-in automation tool.

CT derived fat measurements6 months

The difference in Visceral Adipose Tissue (cm2) derived from the third lumbar vertebral axial level of pre and 3 to 6 month postoperative CT scans using SliceOmatic software version 5.0 with ABACS L3 Plug-in automation tool.

Pre and Post-operative systemic inflammation6 months

C-reactive protein (CRP)

Pre and Post-operative systemic cellular immune response6 months

Neutrophil to Lymphocyte ratio (NLR)

Short-term post surgical complications6 months

Clavien-Dindo Score for postoperative complications (1-5)

Hospital Stay6 months

Length of hospital stay in days

Quality of Life (General - EQ- 5D- 5L)2 years

EuroQol 5-level EQ-5D version, consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).

Five dimensions are analysed: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored from 1 to 5 ranging from: no problems, slight problems, moderate problems, severe problems and extreme problems.

The patient ticks a box corresponding to indicate their status within each dimension. This results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.

Post-operative quality of life at 6 months and 12 months following surgery using the validated quality of life questionnaire ED-5Q-5L will be assessed as described above.

Quality of Life (Colorectal specific - EORTC QLQ - CR29)2 years

European Organisation for Research and Treatment of Cancer (EORTC) colorectal QoL module QLQ-CR29. The QLQ-CR29 contains 4 multi item scales and 19 single items assessing common symptoms and problems in colorectal cancer. The scales and single item measures range in score from 0 to 100. A high score for the functional scale and functional single-items represents a high level of functioning, whereas a high score for the symptom scales and symptom single-items represents a high level of symptomatology or problems.

Post-operative quality of life at 6 months and 12 months following surgery using the validated quality of life questionnaire EORTC QLQ - CR29

Function6 months

Function as assessed by the Berg Balance scale, sit-to-stand and 6-minute walk test at baseline and approximately 3 months following surgery

Thigh circumference2 years

Difference in thigh circumference both legs (at 15cm above the superior pole of the patella) preoperatively and at 3 month postoperatively.

Bio-impedance measures of body composition2 years

Bio-impedance analysis (BIA) metrics at set time points (baseline, day two post operatively, day twenty-eight post operatively (if in hospital) day of discharge, first post-operative follow u appointment.

Device satisfaction10 weeks

Patient satisfaction with using the NMES device.

Device dose response2 years

Dose response to NMES utilising the patient compliance diary and CT derived data.

Sequential CT changes in body composition5 years

Sequential changes measure on CT over a 5-year follow-up period following surgery

Trial Locations

Locations (1)

London North West University Healthcare NHS Trust

🇬🇧

London, Greater London, United Kingdom

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