Acupressure for Children in Treatment for a Childhood Cancer

Study Overview
=================
Brief Summary
-----------------
Background: Despite advances in symptom management, children undergoing cancer treatment or receiving a chemotherapy-based Hematopoietic Stem Cell Transplant (HSCT) often suffer from moderate to severe symptoms of nausea/vomiting, pain, and fatigue along with psychological distress. Pharmacologic treatments of symptoms can cause side-effects. Patients, parents, and clinicians have expressed interest in including non-pharmacologic approaches to improve symptom management. Acupuncture/acupressure is a promising adjunctive therapy to usual care. More evidence is needed from well-designed trials with larger samples and rigorous designs in order to make definitive recommendations about the routine inclusion of acupressure among pediatric patients being treated for childhood cancer or receiving a HSCT. Design and Methods 100 dyads (one child with one parent/caregiver) will be randomized 1:1 into 2 study arms (50 children in each arm). Arm A participants will be offered usual care and professional acupressure five times weekly (15-20 minute sessions) and a parent/caregiver will be instructed in acupressure delivery for the child as symptoms arise. Arm B participants will receive usual care alone. (At the study end, Arm B parents will be offered acupressure instructions.) Children will be enrolled for  30 days which can occur with one month of continuous hospital-based treatment or two months of intermittent hospital-based treatment (inpatient or regular outpatient treatment). Parent and child participants will receive a follow-up interview one month after completion of the intervention (Arm A) or the final symptom assessment (Arm B). Significance This is the first study to evaluate the effectiveness and safety of an acupressure intervention to decrease treatment-related symptoms in 100 patients in treatment for a childhood cancer or receiving a chemo-therapy based HSCT.

Detailed Description
-----------------
AIMS Aim 1: To assess the feasibility of an acupressure intervention plus usual care and to assess the benefits and risks compared to usual care alone for children receiving hospital-based treatment for a childhood cancer or a HSCT. The study hypothesizes that patients in the acupressure arm will report decreased nausea/vomiting and improved management of treatment -related symptoms compared to the usual care only arm. We will test the following hypotheses: 1a. Primary outcomes: Children receiving acupressure will report reduced nausea/vomiting measured as a composite variable compared to the usual care alone group. 1b. Secondary outcomes: Children receiving the acupressure intervention will have reduced levels of each; nausea, vomiting, and rescue antiemetic use compared to the usual care alone group. 1c. Secondary outcomes: Children receiving acupressure will report reduced pain interference and pain intensity, reduced fatigue, anxiety, depression, other treatment-related symptoms, and greater positive affect compared to the usual care group. Children receiving acupressure will use less rescue pain medication compared to the usual care alone group. d. Greater dose of acupressure will lead to greater improvement of primary and secondary outcomes. Aim 2: To assess the benefits and challenges of providing the acupressure intervention for parents. a. The parent/caregiver in Arm A will report decreased post-traumatic stress symptoms, reduced anxiety and depression, and increased caregiving self-efficacy 4 weeks after the end of professional acupressure. 2b. An open-ended question for parents/caregivers in the intervention arm will elicit information on the experience of providing acupressure for their children. Additional Qualitative Aims: Qualitative Aim 1: To explore the child's experience of receiving acupressure and the caregiver's experience of delivering acupressure to the child through a semi-structured interview with the caregiver, with a focus on well-being. We will explore how acupressure impacts the proposed components of well- being: hedonistic and eudemonic perspectives of positive feelings, as well as the less studied somatic and physical components such as mind-body integration and increased connection through touch in the child and caregiver. Qualitative Aim 2: To explore the acupressure provider's impression of how provider- or caregiver- delivered acupressure impacts the child's experience of childhood cancer treatment or HSCT. DESIGN The goal of the study is to describe the benefits and risks of an acupressure intervention to decrease nausea/vomiting and other treatment-related symptoms compared to a control group receiving usual care. This study is a pragmatic randomized clinical trial. Participants will be randomized 1:1 into 2 study arms. In Arm A children will be offered professional acupressure five times weekly along with usual care for  30 days of hospital-based treatment (continuous in-hospital) or two months of hospital-based treatment (intermittent) for an approximate total of 20 semi-standardized acupressure treatments. Treatments take approximately 20 minutes each. A parent/caregiver will be instructed in how to deliver acupressure to his/her child as symptoms arise using a simplified protocol with supplemental educational handouts. In Arm B participants will receive usual care alone. All usual care is defined according to COG supportive care guidelines. After the final study assessment parents/caregivers will be given instruction on how to deliver acupressure. Outcomes will be assessed in all children in Arm A and Arm B at baseline, 5 days a week for nausea, vomiting, and pain, two times a week for remaining symptoms, and at a once month follow-up. Outcomes will be assessed in caregivers at baseline,  day 7, and at follow-up.

Official Title
-----------------
Acupressure Intervention to Reduce Treatment-related Symptoms in Children With Cancer or Receiving a Hematopoietic Stem Cell Transplant

Conditions
-----------------
Treatment-Related Cancer

Intervention / Treatment
-----------------
* Other: Acupressure for Children in Treatment for a Childhood Cancer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children who are either receiving treatment for diagnosis of a childhood cancer (curative or supportive care) or are receiving a chemotherapy-based HSCT. Non-malignant brain central nervous system tumors are considered as a childhood cancer. Ages 5- 24 years old. Be receiving hospital-based treatment (inpatient or outpatient) so that acupressure treatments can be delivered and parents can be trained and monitored. Availability and willingness of a parent or caregiver to deliver acupressure for ages 5-17. For young adults ages 18-24 participation of a parent, close friend or family member/caregiver is preferred but not required. English or Spanish speaking. Receiving treatment at UCSF Benioff Children's Hospital. Exclusion Criteria 1) Children/young adults who meet the above criteria, but whose treating oncologist, health care provider, or a study investigator advises against study participation for physical health, mental health (parent or child) or logistical reasons.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 24 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pragmatic Randomized Controlled Trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Acupressure for Children in Treatment for a Childhood Cancer + usual care | Other: Acupressure for Children in Treatment for a Childhood Cancer<br>* This study will describe the benefits and risks of an acupressure intervention to decrease nausea/vomiting and other treatment-related symptoms compared to a control group receiving usual care. Children in Arm A will receive usual symptom management care + acupressure 5 days/week for  20 treatments. Parents will be taught how to provide acupressure as well. Children in Arm B will receive usual care alone.<br>|
| No Intervention: Arm B<br>Usual care alone | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in nausea/vomiting severity | assessed using the Pediatric Nausea Assessment Tool (PeNAT)(Dupuis, 2006)(see description below) + a single Question on vomiting for ages 5-17. The MASCC Anti-emesis Tool (MAT) will be used to assess nausea (yes/no) and severity for ages 18+.This composite measure of nausea/vomiting in the child represents a continuum of nausea/vomiting (range=1-8). | past 24 hours for nausea/vomiting measures daily over 30 days of hospital-based treatment (continuous hospitalization or intermittent treatment over 2 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decreased nausea (PeNAT) | Nausea will be measured using the PeNat scale, validated for ages 4-17 years. Four levels of nausea are defined on this scale: none, mild, moderate and severe, using faces, a preferred method of measuring distress among children. In the case where a child cannot report on nausea, parent report will be sought. Parents report of child's nausea severity was found to be significantly correlated with child reports. Patients ages 18-24 will be given the MAT. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased vomiting (Vol, 2016) | Vomiting episodes will be measured as recorded by patients and families using patient diaries (confirmed using review of daily patient electronic medical records (EMR)). Vomiting episodes will be capped so the range will be 1-4+ episodes in the 2 day time-span since the last assessment. Using these two variables we can construct a variable for no nausea and no vomiting which is typically called complete control and is a standard outcome for many pharmaceutical antiemetic trials. | 30 days hospitalization (continuous or intermittent over 2 months) | 
| Use of fewer rescue anti-emetics (from Electronic Medical Records) | This will be categorized as a 1-4+ variable where 1=no rescue antiemetic use and 4+ means that a dose was taken 4 or more times between assessments. (Emetogenicity will be assessed using the newest guidelines.) From electronic medical records (EMR). | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Complete control of nausea/vomiting | Using the nausea and vomiting variables we will construct a dichotomous variable for no nausea and no vomiting which is typically called complete control and is a standard outcome for many pharmaceutical antiemetic trials. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased pain interference assessed using the PROMIS Pediatric Pain Interference Scale | (4 items) from the Pediatric Profile 25 v. 2. Pediatric or Parent Proxy Versions assess pain interference in the context of daily activities including interference on physical, psychological and social functioning. (Varni, 2010) | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased Pain intensity | PROMIS Pediatric or Parent Proxy Version includes 1 question that assesses intensity of pain on a 0-10 scale. This single-item pain intensity question is included in the Pediatric Profile 25 v2 and is not scored but reported using a raw score (e.g., 0 to 10). | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased pain assessed (ages 5-7) | Faces Pain (Intensity) Scale-Revised (FPS-R)(1 item) children rank severity of pain using 6 gender-neutral faces depicting 'no pain' to 'most pain'; scores range from 0 to 10. | 30 days of hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased fatigue symptoms | PROMIS Pediatric Profile 25 v2. This 4-item scale includes two domains: feeling tired and (lack of) energy and its impact on daily life. | 30 days of hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased depression symptoms | (4 items) from PROMIS pediatric profile 25 v 2.0 Among young adults aged 18+. 4-item subscales of PROMIS Adult Profile 29 v2.0 will be used. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased anxiety | (4 items) from PROMIS pediatric profile 25 v 2.0 | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Increased Well-being | PROMIS Pediatric Positive Affect measure. This measures positive emotions (well-being) which can reduce experience of symptom burden and protect health. (4 items) Among parents/caregivers the study used Positive Affect Subscale of the PANAS (5-items): This positive affect sub-scale of the 10-item PANAS scale (i-PANAS-SF) assesses positive or pleasurable engagement with the environment, well-being, and satisfaction with life. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Fewer overall symptoms assessed using the Symptom Screening in Pediatrics (SSPedi) tool (Tomlinson, 2014) | This pediatric cancer-specific symptom screening and assessment scale measures physical and psychological symptoms (e.g., feeling angry, sad or worried, tired, mouth sores, headache, constipation or diarrhea, problems thinking or remembering, body changes, or appetite loss, among others) in 15 questions. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased depression symptoms using the PROMIS depression (adult) measure. | 4 item measure used to assess depression among the child's parent/caregiver using subscales of PROMIS Adult Profile 29 v2.0 will be used. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Decreased anxiety assessed using PROMIS anxiety (adult) | 4 item measure used to assess anxiety among the child's parent/caregiver using subscales of PROMIS Adult Profile 29 v2.0 will be used. | 30 days hospital-based treatment (continuous or intermittent over 2 months) | 
| Fewer PTSD symptoms, (PCL-5) (adult) | the Post-traumatic Stress Disorder Checklist is a 20 item measure - updated to use DSM5 criteria. Responses assess frequency and intensity of symptoms (strong internal consistency, test-retest reliability and validity). Total symptom scores will be compared between groups. | 1 month after end of 30 days trial enrollment | 
| Increased Caregiver Self-Efficacy (parent) | This 6 item scale is adapted from Bandura, 1977, Lorig, 1989; Barlow, 2000) and previously used in parents of children with disabilities (excellent psychometric reliability and validity). | 1 month after end of 30 day trial enrollment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nausea, vomiting, pain, fatigue, depression, anxiety, PTSD-parent, caregiver self efficacy-parent