Whole-body Vibration Training to Reduce the Symptoms of Chemotherapy-induced Peripheral Neuropathy (VANISH)

Effects of Individually Tailored Whole-body Vibration Training on the Symptoms of Chemotherapy-induced Peripheral Neuropathy: a Randomized-controlled Trial

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically meaningful side effect of cancer treatment. It is induced by neurotoxic chemotherapeutic agents, causing severe sensory and/or motor deficits such as pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control, insecure gait, and higher risk of falling. It is associated with significant disability and poor recovery, not only reducing patients' autonomy and quality of life but also limiting medical cancer therapy, which subsequently may affect the clinical outcome and compromise survival. To date, CIPN cannot be prevented and approved and effective treatment options are lacking.

Promising results regarding CIPN have recently been achieved with exercise. Own preliminary work revealed that patients profit from sensorimotor training (SMT), experiencing significant relief from CIPN induced symptoms. In a pilot study we therefore also evaluated whole body vibration training, a further neuromuscular stimulating exercise intervention. Results suggest that whole body vibration (WBV) is not only feasible and safe for neuropathic cancer patients but can attenuate motor and sensory deficits.

We therefore propose a two-armed, multicenter, randomized controlled trial (RCT with a follow-up period), including 44 patients with neurologically confirmed CIPN, in order to evaluate the effects of WBV on the relevant symptoms of CIPN. Primary endpoint is the patient reported reduction of CIPN-related symptoms (FACT-GOG-Ntx). Secondary endpoints will include compound muscle action potentials, distal motor latency, conduction velocity, and F-waves from the tibial and peroneal nerve as well as antidromic sensory nerve conduction studies of the sural nerve, feasibility, non-invasive electromyographic (EMG) activity of mm. tibialis anterior, soleus, gastrocnemius medialis, rectus femoris, vastus medialis and biceps femoris, peripheral deep sensitivity, proprioception, balance control as well as pain, quality of life and the level of physical activity. Patients will be assessed before and after a 12 week intervention and again after 12 weeks of follow-up. Interim tests will be performed 6 weeks into the intervention as well as every 3 weeks during the follow-up.

We hypothesize that individually tailored whole body vibration training will reduce relevant symptoms of CIPN. Our results could contribute to improve supportive care in oncology, thereby enhancing patients' quality of life and coincidentally enabling the optimal medical therapy.

Study Overview

• Status: Unknown
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Behavioral: Whole-body vibration training

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4052
    • Recruiting
    • University of Basel
    • Contact: Fiona Streckmann, PhD; Email: fiona.streckmann@unibas.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• oncological patients with neurologically confirmed CIPN
• age: 18-80 years
• performance status of 0-2 according to the toxicity and response criteria of the Eastern Cooperative Oncology Group
• patients underwent neurotoxic chemotherapy with one of the following agents: Taxanes (docetaxel with a cumulative dose of ≥ 225mg/m2 or paclitaxel with a cumulative dose of ≥ 525mg/m2), Vinca-alkaloids (vincristine with a cumulative dose of ≥ 4.2mg/m2 or vinblastine with a cumulative dose of 24mg/m2), Platinum-derivatives (Oxaliplatin with a cumulative dose of ≥ 510mg/m2, Cisplatinum with a cumulative dose of ≥ 200mg/m2)

Exclusion Criteria:

• pre-existing neuropathy of other cause (e.g. diabetes)
• given contraindications for WBV (instable osteolysis, osteosynthesis, acute thrombosis, foot ulcers and a fracture of a lower extremity in the last two years)
• a myocardial infarction, angina pectoris or heart disease (NYHA III-IV) within the past six months
• a mental condition or lack of the German language that prevents the understanding of the written informed consent
• metastases of the central nervous system and epilepsy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Patients in the intervention group will receive a defined exercise program twice a week in addition to their usual treatment. Training sessions start immediately after randomization and will be supervised by trained sport students. They will take place twice a week, for twelve weeks in specific training rooms designed to meet the needs of oncological patients in the respective centers. The vibration exercises will take place on a side-alternating vibration platform (GalileoTM, Pforzheim, Germany) ®) according to the previously determined optimal (highest neuromuscular response) setting for each individual. Each session will last for about 15 to 30 minutes, leaving sufficient time for regeneration. Training will consist of four vibration exercises, chosen from a standardized pool of exercises with increasing difficulty in order to allow for individual, optimal progression. All sessions will be documented by the supervisor.	Behavioral: Whole-body vibration training; Whole-body vibration exercise
No Intervention: Control; Patients in the control group will receive treatment as usual and will be given the opportunity to participate in the intervention after completion of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FACT/GOG-Ntx questionnaire [Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity]	It will be used to document and assess the severity of the subjective peripheral neuropathy (PNP) symptoms. This questionnaire has been validated and is widely applied in clinical practise. It contains eleven items which allow an assessment of the extent of PNP symptoms - from "not at all" to "very much".	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compound muscle action potentials (CMAP)	obtained from the tibial and peroneal nerve	Baseline
Distal motor latency	obtained from the tibial and peroneal nerve	Baseline
Nerve conduction velocity	obtained from the tibial and peroneal nerve	Baseline
Sensory nerve action potentials (SNAPs)	recorded from the lateral malleolus with surface electrodes	Baseline
Peripheral deep sensitivity	evaluated with a Rydel-Seiffer tuning fork (128Hz) on a scale from 0 to 8; due to age related neural deconditioning, values ≤4 are pathological for patients ≥ 60years old, while for patients under 60 years old, ≤5 is regarded as pathological	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Reflex action	The Achilles tendon reflex as well as the patellar tendon reflex is assessed with a reflex hammer and graded on a 3 point scale (1=agile, 2=weak, 3=missing).	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Sense of position	This test examines whether patients can recognize a change of position in their first toe, with their eyes closed.	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Perception of touch	The examiner symmetrically strokes the outsides of the patients' legs and feet in order to detect reduced or altered sensation due to demyelination or axonal degeneration.	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Muscular strength	The strength of the leg muscles is assessed by requesting the patient to actively move their legs against the resistance of the examiner's arm. The examiner then grades the strength on a six point scale (0=no activity, 1=visual contraction without motor effect, 2=movement under elimination of gravity, 3=movement under gravity, 4=movement against slight resistance 5=normal force).	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
EMG recordings	Normalized (to static standing without vibration condition) integrated EMG activity of mm. tibialis anterior, soleus, gastrocnemius (medial head), mm. rectus femoris, vastus medialis, biceps femoris. EMG recordings will be performed using bipolar Ag/AgCl surface electrodes placed over the mm. soleus, gastrocnemius medialis, tibialis anterior, rectus femoris, vastus medialis and biceps femoris of the right leg. A reference electrode will be placed on the patella. To keep interelectrode resistance below 2 kOhm, the skin areas for the electrodes will have to be shaved, degreased and slightly abraded. The EMG signals will then be transmitted to the amplifier (band-pass filter 10 Hz-1 kHz, 1,0009 amplified) via shielded cables and recorded with 4 kHz.	1 week (first 2 training sessions)
CIPN-related pain	Visual analogue scale (VAS) in order to assess neuropathic pain as well as the dysesthesias	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Postural control	Center of pressure during upright static and dynamic stance	Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Quality of life - questionnaire		Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up
Physical activity questionnaire		Change over the course of the study, from baseline to post 12-week intervention to post 12-week follow-up

Collaborators and Investigators

• Sponsor: University of Basel
• Collaborators: University Hospital, Basel, Switzerland; University Hospital of Cologne; German Sport University, Cologne; University of Freiburg
• Investigators: Principal Investigator: Fiona Streckmann, PhD, University of Basel

Publications and helpful links

General Publications

• Streckmann F, Hess V, Bloch W, Decard BF, Ritzmann R, Lehmann HC, Balke M, Koliamitra C, Oschwald V, Elter T, Zahner L, Donath L, Roth R, Faude O. Individually tailored whole-body vibration training to reduce symptoms of chemotherapy-induced peripheral neuropathy: study protocol of a randomised controlled trial-VANISH. BMJ Open. 2019 Apr 24;9(4):e024467. doi: 10.1136/bmjopen-2018-024467.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimate): January 26, 2017

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: March 8, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: 2016-01527

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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