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

BiCyCLE: Neuro-Muscular Electrical Stimulation (NMES) and Its Effect on Changes in Body Composition Following Surgery for Locally Advanced Rectal Cancer - a Single Centre Double Blind Randomised Controlled Phase II Clinical Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Rectal Cancer; Sarcopenia; Advanced Cancer; Colon Cancer; Colo-rectal Cancer; Sarcopenic Obesity; Recurrent Rectal Cancer
• Intervention / Treatment: Device: Microstim 2v2 Stimulator

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, HA1 3UJ
      • London North West University Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neuro-Muscular electrical stimulation treatment arm; Active muscle stimulation with a view that this will lead to muscle preservation through muscle fibre recruitment	Device: Microstim 2v2 Stimulator; Neuro-muscular electrical stimulator portable device (9v battery) connected to the skin participant over the muscle body of choice using self adhesive electro-gel pads. Treatment devices and placebo devices.
Sham Comparator: Neuro-Muscular electrical stimulation Placebo arm; Stimulator set at a sub therapeutic threshold so as to not recruit muscle fibres	Device: Microstim 2v2 Stimulator; Neuro-muscular electrical stimulator portable device (9v battery) connected to the skin participant over the muscle body of choice using self adhesive electro-gel pads. Treatment devices and placebo devices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean muscle attenuation pre and postoperatively	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CT derived muscle measurements	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.	6 months
CT derived fat measurements	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.	6 months
Pre and Post-operative systemic inflammation	C-reactive protein (CRP)	6 months
Pre and Post-operative systemic cellular immune response	Neutrophil to Lymphocyte ratio (NLR)	6 months
Short-term post surgical complications	Clavien-Dindo Score for postoperative complications (1-5)	6 months
Hospital Stay	Length of hospital stay in days	6 months
Quality of Life (General - EQ- 5D- 5L)	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.	2 years
Quality of Life (Colorectal specific - EORTC QLQ - CR29)	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	2 years
Function	Function as assessed by the Berg Balance scale, sit-to-stand and 6-minute walk test at baseline and approximately 3 months following surgery	6 months
Thigh circumference	Difference in thigh circumference both legs (at 15cm above the superior pole of the patella) preoperatively and at 3 month postoperatively.	2 years
Bio-impedance measures of body composition	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.	2 years
Device satisfaction	Patient satisfaction with using the NMES device.	10 weeks
Device dose response	Dose response to NMES utilising the patient compliance diary and CT derived data.	2 years
Sequential CT changes in body composition	Sequential changes measure on CT over a 5-year follow-up period following surgery	5 years

Collaborators and Investigators

• Sponsor: London North West Healthcare NHS Trust
• Investigators: Principal Investigator: Edward T Pring, BSc MRCS, LNWUH NHS Trust

Publications and helpful links

General Publications

• Malietzis G, Currie AC, Johns N, Fearon KC, Darzi A, Kennedy RH, Athanasiou T, Jenkins JT. Skeletal Muscle Changes After Elective Colorectal Cancer Resection: A Longitudinal Study. Ann Surg Oncol. 2016 Aug;23(8):2539-47. doi: 10.1245/s10434-016-5188-1. Epub 2016 Mar 22.
• Malietzis G, Johns N, Al-Hassi HO, Knight SC, Kennedy RH, Fearon KC, Aziz O, Jenkins JT. Low Muscularity and Myosteatosis Is Related to the Host Systemic Inflammatory Response in Patients Undergoing Surgery for Colorectal Cancer. Ann Surg. 2016 Feb;263(2):320-5. doi: 10.1097/SLA.0000000000001113.
• Malietzis G, Currie AC, Athanasiou T, Johns N, Anyamene N, Glynne-Jones R, Kennedy RH, Fearon KC, Jenkins JT. Influence of body composition profile on outcomes following colorectal cancer surgery. Br J Surg. 2016 Apr;103(5):572-80. doi: 10.1002/bjs.10075.
• Grande AJ, Silva V, Maddocks M. Exercise for cancer cachexia in adults: Executive summary of a Cochrane Collaboration systematic review. J Cachexia Sarcopenia Muscle. 2015 Sep;6(3):208-11. doi: 10.1002/jcsm.12055. Epub 2015 Jul 7.
• Maddocks M, Lewis M, Chauhan A, Manderson C, Hocknell J, Wilcock A. Randomized controlled pilot study of neuromuscular electrical stimulation of the quadriceps in patients with non-small cell lung cancer. J Pain Symptom Manage. 2009 Dec;38(6):950-6. doi: 10.1016/j.jpainsymman.2009.05.011.
• Pring ET, Gould LE, Malietzis G, Lung P, Bharal M, Fadodun T, Bassett P, Naghibi M, Taylor C, Drami I, Chauhan D, Street T, Francis NK, Athanasiou T, Saxton JM, Jenkins JT; BiCyCLE Research Group. BiCyCLE NMES-neuromuscular electrical stimulation in the perioperative treatment of sarcopenia and myosteatosis in advanced rectal cancer patients: design and methodology of a phase II randomised controlled trial. Trials. 2021 Sep 15;22(1):621. doi: 10.1186/s13063-021-05573-2.

Helpful Links

• Trial Website

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2019
• Primary Completion (Actual): March 6, 2021
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Sarcopenia; Rectal Cancer; Myosteatosis; Myopenia; Recurrent Rectal Cancer; Advanced Rectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Intestinal Neoplasms; Rectal Diseases; Muscular Atrophy; Atrophy; Colorectal Neoplasms; Rectal Neoplasms; Sarcopenia
• Other Study ID Numbers: 242022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan at present for data sharing however patients will consent for fully anonymised data sharing to occur. No identifiable information will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No