Cryotherapy for Prevention of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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Oral mucositis (OM) is a common adverse effect of chemotherapy, radiotherapy and conditioning regimens before Hematopoietic Stem Cell Transplantation (HSCT). The aim of this study is to effectiveness of cryotherapy as a prophylactic treatment in children undergoing HSCT.

Detailed Description
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There is a complex pathobiology behind OM; chemo and radiotherapy affects the mucosa and submucosa causing DNA-strand brakes and generation of reactive oxygen species (ROS). This initiates a cascade of events, among others activation of transcription factors, up-regulation of pro-inflammatory cytokines, and activation of macrophages and proteases leading to tissue injury causing symptoms such as erythema, edema, ulceration, taste perception alterations, and mouth dryness. OM often causes local and systemic infections, fatigue, pain, and difficulties in basal functions such as swallowing (and hence drinking and eating) and talking and reduces patients' psychological well-being. Nearly 90 % of pediatric patients undergoing HSCT are afflicted with OM. In pediatric patients mucositis is reported as one of the most painful and debilitating side effects during cancer treatment.Beyond a significant suffering for the patient it is hence associated with higher costs for health care and increased mortality. The current scientific situation regarding prevention and treatment of OM has been summarized in Cochrane reports showing limited data on adults and practically missing data on children and adolescents. Concluding guidelines from these reports emphasize the need for well conducted randomized controlled trials (RCT's) to evaluate and refine treatments in order to establish evidence based interventions. The use of cryotherapy to prevent oral mucositis in patients who are receiving high-dose chemotherapy as a conditioning agent prior to HSCT continue to show evidence in the adult population. The aim of this study is to compare treatment with cryotherapy (Arm 1)with a standard oral care protocal (Arm 2) ARM 1 Children are instructed to use chew on ice-chips, ingest ice-cream or ice-water during infusion of chemotherapy as part of the conditioning treatment prior to HSCT. Melted ice should be replaced by new as soon as possible. Children receiving a 24-hour infusion are instructed to use cryotherapy for one hour 4 times a day. ARM 2 Standard care for prevention and management of oral mucositis Primary outcome Degree and duration of Oral mucositis Secondary outcomes Oral pain Opioid use Duration of parenteral nutrition Weight loss Duration of neutropenic fever Duration of antibiotic treatment Duration of hospitalization Emotional and psychological status C reactive protein (CRP) and s-albumin correlation to grade of Oral Mucositis

Official Title
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A Randomized Controlled Trial of Cryotherapy for Prevention and Reduction of Severity of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation.

Conditions
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Oral Mucositis, Pain, Infection, Nutrition Aspect of Cancer

Intervention / Treatment
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* Other: Cryotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 4-18 Undergoing Hematopoietic Stem Cell Transplantation in Sweden sufficient knowledge in swedish to understand the protocols - Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryotherapy<br>Cryotherapy during conditioning treatment with chemotherapy prior to HSCT | Other: Cryotherapy<br>* Cryotherapy with ice-chips, ice cream or ice water is given during conditioning treatment with chemotherapy prior to HSCT.<br>|
| No Intervention: Control<br>Standard oral Care. No Cryotherapy during conditioning treatment prior to HSCT | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucositis grade - WHO Oral Toxicity Scale | WHO-Oral toxicity scale Grade 0 - No mucositis Grade 1 - Erythema and/or soreness Grade 2 - Erythema and/or ulcers. Can eat solid food. Grade 3 - Erythema and/or Ulcers. No solid food but can ingest liquids. Grade 4 - Oral alimentation not possible. | Daily until engraftment, an expected average of 20 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucositis grade - Children´s International Mucositis Evaluation Scale (ChiMES) | Daily evaluation by child and parent. | Daily until engraftment, an expected average of 20 days. | 
| Pain - Childrens Hospital Eastern Ontario Pain Scale (CHEOPS) | Daily assessment by nurse | Daily until Engraftment an expected average of 20 days. | 
| Mouth Pain | Mouth Pain measured with Numerical Rating scale(NRS)for children >7 years and parents and Facial Pain Scale(FPS) for children < 7 years | Daily until Engraftment an expected average of 20 days | 
| Emotional and Psychological status | Beck youth inventories for depression and anxiety | Daily until engraftment, an expected average of 20 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Mucositis, Children, Cryotherapy, Hematopoietic Stem Cell Transplantation