Preventing Sensory and Motor Dysfunctions in Children Receiving Neurotoxic Chemotherapy (PrepAIR)

Preventing Sensory and Motor Dysfunctions in Children Receiving Neurotoxic Chemotherapy - a Randomized Controlled, Multi-center Trial

The investigators would like to conduct a prospective, multicenter, two-armed trial (RCT with follow-up). Patients will be recruited from 7 centers (CH/D). All patients (and their guardians) scheduled to receive chemotherapy containing either a platinum derivate or vinca-alkaloid, will be asked to participate. Willing patients will then be randomized either into an intervention group or a control group. Patients in the intervention group will perform a standardized, age-adjusted, specific playful sensorimotor training (SMT) program twice a week for the duration of their medical therapy, in addition to usual care, while the control group receives treatment as usual. The CG will be given the opportunity to participate in the intervention after therapy. Data will be assessed at 3-4 time points: Prior to chemotherapy (baseline T0), after 12 weeks (T1), after completion of therapy for children that are treated >3 months (Tp) and after 12 months follow-up (T3). Additionally, status of Chemotherapy-induced peripheral neuropathy (CIPN) reported symptoms will be monitored twice in-between (6 weeks).

The investigators hypothesize that less children in the intervention group will develop symptoms of CIPN (TNS score) with its debilitating side-effects. Furthermore, children in the intervention group will be able to maintain relevant motor and sensory functions and their associated physical functions which will enable them to receive their planned medical therapy but also to stay on the age-appropriate motor development level, improve their quality life and enhance social reintegration after therapy.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Cancer; Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Behavioral: Playful sensorimotor training

Detailed Description

Modern therapy has improved survival for children with cancer. However, treatment has unintended consequences. Depending on the neurotoxic agent (platinum derivates or vinca-alkaloids), 52%-100% of children develop a peripheral neuropathy. Diagnosis is underreported and its impact as potentially initial cause for many sensory and motor symptoms underestimated. The severe symptoms such as loss of sensation, numbness, pain, absent reflexes as well as loss of balance control not only delays motor development milestones such as walking, running, jumping or climbing, diminishing children's quality of life and affecting their social reintegration, but is also of high clinical relevance. Additionally, recovery is poor and there are currently no effective options to prevent or treat the symptoms of Chemotherapy-induced peripheral neuropathy (CIPN). Promising results have so far been achieved with specific exercise interventions.

The investigators would therefore like to conduct a prospective, multicenter, two-armed trial (RCT with follow-up). Patients N=131 will be recruited from 7 centers: University Children's Hospital of Basel, the Inselspital Bern, Kantonsspital Aarau, Children Hospital for Eastern Switzerland St. Gallen, University Children Hospital Freiburg and the National Center for tumor diseases (NCT), University Children Hospital Heidelberg, Charité Berlin. All patients (and their guardians) scheduled to receive chemotherapy containing either a platinum derivate or vinca-alkaloid, will be asked to participate. Willing patients will then be randomized either into an intervention group or a control group (CG). Patients in the intervention group will perform a standardized, age-adjusted, specific playful sensorimotor training (SMT) program twice a week for the duration of their medical therapy, in addition to usual care, while the control group receives treatment as usual. The CG will be given the opportunity to participate in the intervention after therapy. Data will be assessed at 3-4 time points: Prior to chemotherapy (baseline T0), after 12 weeks (T1), after completion of therapy for children that are treated >3 months (Tp) and after 12 months follow-up (T3). Additionally, status of CIPN reported symptoms will be monitored twice in-between (6 weeks). The investigators hypothesize that less children in the intervention group will develop symptoms of CIPN (TNS score) with its debilitating side-effects. Furthermore, children in the intervention group will be able to maintain relevant motor and sensory functions and their associated physical functions which will enable them to receive their planned medical therapy but also to stay on the age-appropriate motor development level, improve their quality life and enhance social reintegration after therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 131
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fiona Streckmann, Dr.; Phone Number: +41 061 207 47 30; Email: fiona.streckmann@unibas.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • Not yet recruiting
    • Kantonspital Aarau
    • Contact: Jeanette Greiner, Dr
  • Basel, Switzerland, 4056
    • Recruiting
    • UKBB Kinderspital
    • Contact: Nicolas Von Der Weid; Phone Number: 617042995

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All tumor patients, aged 6-18 years, who are scheduled to receive neurotoxic chemotherapy with a platinum-derivate or vinca- alkaloid (e.g. vincristine, vinblastin mono, carboplatinum, cisplatin).

Exclusion Criteria:

• Exclusion criteria are known neuropathies of other cause (e.g. diabetes), disabilities or lack of German language that prevent the understanding of the informed consent as well as the instructions for training.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Patients in the intervention group will perform a standardized, age-adjusted, specific playful sensorimotor training (SMT) program twice a week for the duration of their medical therapy, in addition to usual care.	Behavioral: Playful sensorimotor training; For the max. duration of the first in-hospital phase (3weeks), all children will receive supervised training. When children go home they will be supplied with a manual, specific exercises and the necessary training devices. Regular supervision will allow to ensure that the training is performed at maximum benefit. Each session will last for about 20 to 30 minutes in total, including a child-specific warm-up and cool-down. The children will be asked to maintain balance in a previously acquired "short-foot-position", knees slightly flexed (30°), without shoes. Training will consist of 5 playful balance exercises chosen from a standardized pool of exercises according to the child's age, with increasing difficulty in order to allow for individual, optimal progression. Each of the 5 exercises will contain of 5 repetitions for 10sec. allowing for a 20sec. rest in between each set and a 1min rest between each exercise in order to avoid neural fatigue.
No Intervention: Control group; The control group receives treatment as usual. The control group will be given the opportunity to participate in the intervention after therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-/Post incidence of neuropathic symptoms via Ped-mTNS score	Primary endpoint is the Ped-mTNS score. It contains a short questionnaire as well as a clinical test battery. The questionnaire is composed of three sets of questions on sensory symptoms and pain, motor function, and autonomic function, and a five- part neurologic exam. The clinical test battery contains light touch sensation, evaluated with Semmes-Weinstein-monofilaments, pin sensibility (MediPin), vibration sensibility assessed with a biothesiometer, deep tendon reflexes of Achilles and patellar tendons and muscular strength examined by a manual muscle test36, each category is rated on a likert scale from 0-4 (0 indicating no symptoms and 4 severe symptoms).	Baseline (T0), subjective screening for symptoms of CIPN (via phone cell), 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 Months (TFU)
Pre/Post change of signs and symptoms of a neuropathy (VAS (0-10))	Signs and symptoms of CIPN	Baseline (T0), Screening for symptoms of CIPN (via phone cell), 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 Months (TFU)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcomes - Pre/post change of postural control	postural control - sway path on the Leonardo force plate	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of Dorsiflexion	dorsiflexion function, assessment of foot drop with a goniometer and hand-held dynamometer	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of strength in the lower extremity - knee extension	knee extension strength will be assessed with a hand-held dynamometer	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of lower limb power	lower limb power will be assessed with the countermovement jump	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of gait speed	10m walk test / walk to run transition time	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of neuropathic pain	CIPN-related pain will be assessed on a child-appropriate visual analogue scale (VAS)	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of level of physical activity	participation of exercise-related leisure activities	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of physical self-concept	childrens' physical self concept via questionnaire	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)
Pre/post change of patients' self-reported, health-related quality of life	childrens quality of life via questionnaire	Baseline (T0), after 12 weeks (T1), within 7days after last dosage of medical therapy (Tp), 12 months after last dose of Chemotherapy (TFU)

Collaborators and Investigators

• Sponsor: University of Basel
• Collaborators: Charite University, Berlin, Germany; University Hospital Inselspital, Berne; Kantonsspital Aarau; University Hospital Heidelberg; University Hospital Freiburg; Krebsforschung Schweiz, Bern, Switzerland; Clinical Trial Unit, University Hospital Basel, Switzerland; National Center for Tumor Diseases, Heidelberg; Ostschweizer Kinderspital
• Investigators: Principal Investigator: Fiona Streckmann, Dr., University of Basel, Department of Sport, Exercise and Health

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): March 31, 2025
• Study Completion (Anticipated): March 31, 2026

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: November 3, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Exercise; Cancer; Children; Lymphoma; Leukemia; Non-Hodgkin Lymphoma; Chemotherapy-induced peripheral neuropathy; CIPN; Sensorimotor Training
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: 2021-00527

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: data will be shared on request after completion of the study
• IPD Sharing Time Frame: data will be available after completion of the study and publication of the first manuscript
• IPD Sharing Access Criteria: on demand
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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