The Effect of Cold Therapy on Peripheral Neuropathy
The Effect of Cold Therapy on Peripheral Neuropathy: A Pilot Randomized Controlled Trial
This study examines the feasibility, acceptability, and efficacy of cold therapy on vincristine-induced peripheral neuropathy (VIPN) in pediatric patients with cancer.
Vincristine (VCR) is one of the most used vinca alkaloid chemotherapy in pediatric oncology patients. It leads to symptoms of peripheral neuropathy, numbness in the hands and feet, tingling, muscle/joint pain, burning sensation, decreased peripheral reflexes, and constipation. These symptoms negatively affect the daily life and quality of life of children. Therefore, it is essential to managing peripheral neuropathy. We aim to decrease the level of VIPN and pain and improve patients' quality of life.
Unfortunately, the neurotoxicity mechanisms of vinca alkaloids are not well known, which is one of the significant limitations in developing effective treatments to prevent VIPN among pediatric oncology patients. We were unable to locate a randomized controlled trial that has evaluated the effectiveness, tolerability, and acceptability of cold therapy on VIPN for pediatric oncology patients. Our study findings will be the first in Turkish national and international literature, and we believe that our results will provide evidence for clinical nursing practice.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
An estimated 400,000 children and adolescents aged 0-19 years are diagnosed with cancer each year. More than 80% of children with cancer are cured in high-income countries, where comprehensive care is generally available, whereas survival remains below 30% in some low- and middle-income countries. Considering the global burden of childhood cancer, it is important to characterize the long-term adverse effects of cancer treatment and to develop strategies for their assessment, monitoring, prevention, and management.
Many chemotherapy agents can cause acute and chronic injury and dysfunction of the peripheral nervous system, termed chemotherapy-induced peripheral neuropathy (CIPN). CIPN is an important treatment-related complication and may affect sensory, motor, and autonomic functions. Peripheral nerve toxicity has been associated with several classes of chemotherapy, including vinca alkaloids, platinum compounds, taxanes, epothilones, bortezomib, and thalidomide. Acute CIPN may develop during chemotherapy and may necessitate dose reduction or treatment discontinuation. Reported CIPN incidence varies considerably according to patient characteristics, treatment regimens, and assessment methods. Common manifestations in children and adolescents include numbness, tingling, neuropathic pain in the upper and lower extremities, weakness, reduced ankle dorsiflexion, foot drop, and impaired balance. These symptoms and associated functional impairments may persist beyond completion of cancer treatment.
Vincristine (VCR) is a vinca alkaloid commonly used in pediatric oncology and is included in chemotherapy regimens for acute lymphoblastic leukemia, lymphomas, neuroblastoma, sarcomas, and central nervous system tumors. Vincristine-induced peripheral neuropathy (VIPN) is characterized by autonomic, sensory, and motor manifestations. Reported rates of VIPN vary substantially, partly because of differences in assessment methods. VIPN symptoms may develop after only a few VCR administrations and can include paresthesia, constipation, muscle weakness, areflexia, neuropathic pain, and sensory loss.
Management of VIPN primarily focuses on symptoms and may include medications used for neuropathic pain. VCR dose reduction or treatment interruption may be required in clinically significant cases, potentially limiting optimal cancer treatment. VIPN and associated neuropathic pain may negatively affect quality of life (QoL) during and after cancer treatment.
Both pharmacological and non-pharmacological approaches have been investigated for the management of peripheral neuropathy. However, the mechanisms underlying chemotherapy-related neurotoxicity are not fully understood, limiting the development of effective strategies for preventing VIPN in pediatric oncology patients. Cryotherapy has been investigated as a potential approach for preventing chemotherapy-induced peripheral neuropathy. Its proposed mechanism involves local vasoconstriction, which may reduce blood flow and consequently decrease chemotherapy exposure in cooled peripheral tissues. Potential limitations of cryotherapy include cold-related skin injury, discomfort or intolerance, practical difficulties with administration, and uncertainty regarding its effectiveness.
Although cryotherapy has been investigated for chemotherapy-induced peripheral neuropathy in adults, evidence regarding its use in children and adolescents with cancer is limited. Further research is therefore needed to evaluate its effectiveness, tolerability, and feasibility in pediatric oncology populations. This study aims to evaluate the effectiveness, tolerability, and acceptability of cold therapy for VIPN among pediatric oncology patients in Turkey.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Istanbul, Turkey (Türkiye)
- Koc University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
Inclusion criteria: (i) aged 7-18 years; the lower age limit of 7 years was selected to ensure reliable completion of the self-report pain and quality-of-life instruments used in the study, (ii) receiving VCR therapy, (iii) diagnosed with leukemia, medulloblastoma, rhabdomyosarcoma, or Wilms tumor, (iv) able to speak and understand Turkish, (v) receiving initial treatment, and (vi) provision of written informed consent by legal guardians and assent from children.
Exclusion criteria: Risk factors for peripheral neuropathy were considered exclusion criteria (Kandula et al., 2016; Smith et al., 2021; van de Velde et al., 2017). Risk factor criteria were: (i) receiving a dose of VCR >2 mg/m2, (ii) receiving VCR and azole antifungal treatment simultaneously, (iii) a hematological malignancy with neurological disease, (iv) a history of peripheral neuropathy, (v) diabetes, or (vi) self-reported cold sensitivity. Additionally, children who received chemotherapy or other treatments via the peripheral veins of the hands or feet were not included, as cold application was contraindicated in these cases.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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No Intervention: Control group
Children in the control group received standard care with no additional intervention for VIPN prevention.
Standard care included gabapentin (5-10 mg/kg/day in 2-3 divided doses, titrated up to 50 mg/kg/day as clinically indicated) and vitamin B6 (150 mg/m²/day in 2 divided doses), according to institutional protocol.
Before the first VCR dose, pain and VIPN were assessed using the Wong-Baker FACES® Pain Rating Scale and NCI CTCAE Peripheral Neuropathy Scale and were assessed weekly thereafter.
QoL was assessed monthly using the child self-report PedsQL 3.0 Cancer Module.
No pre-VCR QoL assessment was performed; thus, the first PedsQL assessment was the first monthly follow-up rather than a true baseline.
Assessments were interviewer-administered by the research assistant.
VCR was administered according to institutional protocol.
Final pain and VIPN were assessed 1 week after the final VCR dose.
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Experimental: Cold Therapy/Intervention Group
In addition to standard care, children in the intervention group received cold therapy during vincristine (VCR) administration using NatraCure Cold Therapy gloves and socks containing gel packs stored at -18°C to -20°C.
Gloves and socks were applied 5 min before VCR administration, maintained throughout the infusion, and continued for 5 min afterward (approximately 15 min/session).
Gel packs were replaced every 5 min to maintain cooling.
Children were monitored for cold-related adverse effects or intolerance, and the intervention was discontinued if necessary.
Pain and VIPN were assessed before the first VCR dose and weekly thereafter using the Wong-Baker FACES® Pain Rating Scale and NCI CTCAE Peripheral Neuropathy Scale.
Quality of life was assessed monthly using the PedsQL 3.0 Cancer Module; no pre-VCR baseline QoL assessment was performed.
Final pain and VIPN outcomes and satisfaction were assessed 1 week after the final VCR dose.
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These gloves and socks will be adjusted and tied to the child's wrists and ankles.
There are sizes suitable for all ages and the dimensions of the gloves and socks can be adjusted with a snap fastener.
The gloves and socks contain a soft Lycra lining and four inner gel cold packs to ensure full length cold therapy treatments.
When the children wear these gloves and socks, they can still move their fingers and toes easily.
In addition, it is a great advantage that the iced gel packs do not touch the child's skin directly.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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National Cancer Institute Common Terminology Criteria for Adverse Events v5 Peripheral Neuropathy Scale
Time Frame: Before starting each VCR application, the child's VIPN in the last week post the previous application will be evaluated. One week after the last VCR dose, the child's VIPN will be evaluated.
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The NCI CTCAE version 5.0 (ctep.cancer.gov)
includes toxicity criteria for adverse events such as peripheral sensory and motor neuropathy, constipation, and neuralgia.
The grading scale, used by health professionals is from 0-5, with 0=no toxicity and 5=death.
In this study, a research assistant (PhD student in pediatric nursing) responsible for data collection will be trained to perform CTCAE scoring, review all medical records, and assign CTCAE version 5.0 sensory and motor scores according to the published criteria based on clinician documentation of signs and symptoms.
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Before starting each VCR application, the child's VIPN in the last week post the previous application will be evaluated. One week after the last VCR dose, the child's VIPN will be evaluated.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Wong-Baker FACES® Pain Rating Scale
Time Frame: Before starting each VCR application, the child's pain in the last week post the previous application will be evaluated. One week after the last VCR dose, the child's pain will be evaluated.
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This scale consists of six facial expressions.
Facial expressions range from 0 points "no pain-very happy" to 10 points "unbearable pain-crying" (Wong-Baker FACES Foundation, 2016).
The self-report scale is commonly used for children aged 3-18 (Martin et al., 2018).
It has good validity and reliability for measuring pain intensity (Ball et al., 2017), and is psychometrically appropriate and widely used in clinical practice (Stinson et al., 2006).
The psychometric properties of this scale are also suitable for evaluation by parent proxy (Schiavenato, 2008).
The scale has been translated into Turkish.
(Wong-Baker FACES Foundation, 2016).
For the present study, the Wong-Baker FACES® scale will be used for evaluating children's self-report and parental reports of the child's pain.
This pain scale is commonly used in Turkey to evaluate children's pain.
It is used as a standard measurement tool in the pain assessment of children aged 3-18 in all pediatric clinics in Turkey.
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Before starting each VCR application, the child's pain in the last week post the previous application will be evaluated. One week after the last VCR dose, the child's pain will be evaluated.
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module Survey
Time Frame: Before starting each VCR application, the child's QoL in the last week post the previous application will be evaluated. One week after the last VCR dose, the child's QoL will be evaluated.
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This scale was developed to measure the health-related QoL of children and adolescents aged 2-18 years (Varni et al., 2002).
The reliability and validity of the Turkish Version of the PedsQL 3.0 Cancer Module testing was performed by Kabak et al. (2016).
The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer-specific health-related QoL.
The 27-item multidimensional PedsQL 3.0 Cancer Module Acute Version encompasses 8 subscales: 1) pain and hurt (2 items), 2) nausea (5 items), 3) procedural anxiety (3 items), 4) treatment anxiety (3 items), 5) worry (3 items), 6) cognitive problems (5 items), 7) perceived physical appearance (3 items), and 8) communication (3 items).
The child self-report and parent-proxy report are filled in considering QoL over the previous seven days.
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Before starting each VCR application, the child's QoL in the last week post the previous application will be evaluated. One week after the last VCR dose, the child's QoL will be evaluated.
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- KOCUNIVERSITY
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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