Clinical trial NCT04065984: Body Composition Manipulation in CoLorectal cancEr (BiCyCLE): Neuromuscular Electrical Stimulation (NMES)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Rectal Cancer
Colorectal Cancer
Colon Cancer
Colo-rectal Cancer
Sarcopenia
Sarcopenic Obesity
Advanced Cancer
Recurrent Rectal Cancer
Keywords: Rectal Cancer
Colorectal Cancer
Recurrent Rectal Cancer
Advanced Rectal Cancer
Myopenia
Sarcopenia
Myosteatosis
Lead sponsor: London North West Healthcare NHS Trust
Sponsor class: OTHER
First posted: 2019-08-22
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean muscle attenuation pre and postoperatively
timeFrame: 2 years
Secondary outcomes:
measure: CT derived muscle measurements
timeFrame: 6 months
measure: CT derived fat measurements
timeFrame: 6 months
measure: Pre and Post-operative systemic inflammation
timeFrame: 6 months
measure: Pre and Post-operative systemic cellular immune response
timeFrame: 6 months
measure: Short-term post surgical complications
timeFrame: 6 months
measure: Hospital Stay
timeFrame: 6 months
measure: Quality of Life (General - EQ- 5D- 5L)
timeFrame: 2 years
measure: Quality of Life (Colorectal specific - EORTC QLQ - CR29)
timeFrame: 2 years
measure: Function
timeFrame: 6 months
measure: Thigh circumference
timeFrame: 2 years
measure: Bio-impedance measures of body composition
timeFrame: 2 years
measure: Device satisfaction
timeFrame: 10 weeks
measure: Device dose response
timeFrame: 2 years
measure: Sequential CT changes in body composition
timeFrame: 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: London North West University Healthcare NHS Trust
state: Greater London
Study officials:
affiliation: LNWUH NHS Trust
name: Edward T Pring, BSc MRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.