Prevention of Chemotherapy-Related Polyneuropathy Via Sensorimotor Exercise Training

NCT02871284 | Completed

• 1 other identifier: S-630/2015/PIC
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy-induced peripheral neurotoxicity (CIPN) as a side effect of chemotherapy negatively affects patients' quality of life and may lead to treatment disturbances. CIPN is frequently recorded in patients treated with alkylating platinum-based drugs, antitubulins including the taxanes and vinca alkaloids, and other drugs including suramin, thalidomide, lenalidomide and the proteasome inhibitor bortezomib, representing one of the most severe and potentially dose-limiting non-hematological toxic effects. Sufficient treatment options or preventive measures are lacking. There is evidence that physical activity strategies are able to address existing CIPN symptoms and potentially increase quality of life in affected patients. CIPN symptoms involves restrictions of sensory and sometimes motor modalities, for example, deficits in plantar perception and dysfunction of postural control and one study in type II diabetes patients also suggested that structured exercise might have a preventive potential with regard to peripheral neuropathy incidence. Based on these findings, we aim to investigate the preventive potential of a sensorimotor intervention vs. machine-based resistance training vs. usual care (wait-list control group) in a randomized controlled three-arm intervention trial among cancer patients undergoing chemotherapy with high risk for CIPN. On the basis of power calculations, the goal is to include 82 patients per intervention arm resulting in a total patients number to be enrolled of n=246. CIPN symptoms will be assessed objectively via comprehensive clinical and electrodiagnostic examinations (Total Neuropathy Scale; TNS-reduced) and subjectively via questionnaires (EORTC QLQ-CIPN20 \& FACT-GOG-Ntx, EORTC QLQ-C30). Additionally CIPN and the effectiveness of the selected interventions will be objectively evaluated by spectral analysis of Centre of Pressure (COP) variations. Further key secondary endpoints are: physical performance, sleep quality and chemotherapy compliance.

Conditions

Exercise; Chemotherapy-induced Polyneuropathy

Keywords

cancer; anticancer treatment; exercise; physical activity; sensorimotor training; chemotherapy-induced polyneuropathy

Outcome Measures

Primary Outcomes (1)

• Total Neuropathy Scale (TNS)

  The TNS is based on symptoms, signs and basic instrumental evaluations and provides a much larger range of scoring values (0 - 40) than common oncological toxicity scales such as the National Cancer Institute (NCI) Common Toxicity Criteria (ranging from 0 - 4, cf. http://ctep.cancer.gov/forms), thus allowing the severity of CIPN to be graded more precisely. The TNS has so far been used to assess the neurotoxicity of various CIPN-relevant chemotherapeutic agents, and its results are clearly correlated with the clinically relevant results of NCI Common Toxicity Criteria, Ajani's and Eastern Cooperative Oncology Group toxicity scales, which are commonly used by oncologists.28-32 Within the PIC-Study the TNS-reduced will the primary endpoint. The TNS-reduced score excludes QST (quantitative sensory testing) vibration testing resulting in a TNS scale from 0-36.

  up to week 24 (and 3 & 6 month follow up)

Secondary Outcomes (9)

• Centre of Pressure (COP)

  up to week 24 (and 3 & 6 month follow up)

• Strength Performance

  up to week 24

• Cardiopulmonary Fitness

  up to week 24 (and 3 & 6 month follow up)

• EORTC QLQ-C30

  up to week 24 (and 3 & 6 month follow up)

• EORTC QLQ-CIPN20

  prior to each Chemotherapy cycle within the first 24 weeks (and 3 & 6 month follow up)

Other Outcomes (1)

• Safety of exercise interventions

  up to week 24

Study Arms (3)

Sensorimotor training (EI)

EXPERIMENTAL

The participants of the experimental intervention arm will take part in a 45 minutes sensorimotor training class two times a week for a maximum of 24 weeks at the NCT (National Center for Tumor Diseases). Highly qualified exercise therapists will guide the class. Class size will be no bigger than 8 patients to ensure adequate individual supervision and guidance. Additionally, participants will be asked to perform one weekly 15 minutes home-based sessions without supervision. Participants who are not able to come to the NCT Heidelberg 2x/week will be offered a home-based sensorimotor program including the same exercises. At the beginning, participants will receive an appointment for an individual face-to-face counseling session at the NCT. During this appointment, the patient will receive an exercise manual for individualized home-based sensorimotor training and a practical introduction by the exercise therapist.

Behavioral: Exercise

machine-based resistance training (AC)

ACTIVE COMPARATOR

Participants of the active control arm will receive machine-based resistance training. The supervised resistance exercise program will be undertaken twice weekly in small groups (not more than 12 people per group) of participants and will be guided by an exercise physiotherapist over a maximum of 24 weeks. All sessions will start with a warm-up and finish with a cool-down (comprising exercise on a cycle ergometer or treadmill at a relatively low intensity and stretching activities) and will take approximately 45 minutes. Additionally, participants will be asked to perform a weekly 15 minutes home-based resistance training session without supervision

Behavioral: Exercise

usual care

NO INTERVENTION

Participants will receive usual care with no additional exercise training or intervention

Interventions

Exercise BEHAVIORAL

Sensorimotor training (EI); machine-based resistance training (AC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosed with cancer and assigned to receive a chemotherapeutic regimen containing at least one of the following agents:
• a platinum analog, e.g., cisplatin, carboplatin, oxaliplatin
• a vinca alkaloid, e.g., vincristine
• a taxane, e.g., paclitaxel, docetaxel
• suramin
• thalidomide or lenalidomide
• bortezomib
• Physical capability that allows the performance of the training program implemented within the experimental intervention or the control intervention arm

You may not qualify if:

• Known polyneuropathy of any kind or any polyneuropathic signs or symptoms at baseline
• Abnormal electroneurographic findings at baseline
• Known metastasis to the central or peripheral nervous system
• Any physical or mental handicap that would hamper the performance of the training program implemented within the intervention arms
• Family history positive for any hereditary polyneuropathy
• Known history of alcohol or illegal drug abuse or any constellation of lab values suggesting alcoholism

Sponsors & Collaborators

• German Cancer Research Center: lead
• University Hospital Heidelberg: collaborator
• National Center for Tumor Diseases, Heidelberg: collaborator

Study Sites (1)

National Center for Tumor Diseases

Heidelberg, 69120, Germany

Location

Related Publications (1)

• Muller J, Weiler M, Schneeweiss A, Haag GM, Steindorf K, Wick W, Wiskemann J. Preventive effect of sensorimotor exercise and resistance training on chemotherapy-induced peripheral neuropathy: a randomised-controlled trial. Br J Cancer. 2021 Sep;125(7):955-965. doi: 10.1038/s41416-021-01471-1. Epub 2021 Jul 5.

  PMID: 34226683 DERIVED

MeSH Terms

Conditions

Motor Activity; Neoplasms

Interventions

Exercise

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: August 18, 2016
• Study Start: April 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: December 1, 2019
• Last Updated: June 1, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)