Clinical trial NCT03399331: Honey or Olive Oil for Treating Oral Mucositis in Children and Adults With Leukemia Receiving Intensive Chemotherapy
Official title: "The Efficacy of Honey or Olive Oil on the Severity and Pain of Oral Mucositis Compared to Placebo (Standard Care) in Children With Leukemia Receiving Intensive Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Oral Mucositis
Leukemia
Keywords: honey, olive oil, oral mucositis, pain
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
Collaborators: name: Azusa Pacific University
name: Daisy Foundation
First posted: 2018-01-16
Enrollment: 45
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: three groups randomized using a computer generted number sequence
Primary purpose: TREATMENT

Brief summary: Background: Oral mucositis (OM) is a significant complication occurring in approximately 40% of patients on chemotherapy regimens. Ulcerative lesions of OM can be very painful, with negative impact on diet, oral hygiene, and quality of life. Although a wide variety of agents have been tested to prevent OM or reduce its severity, none have provided conclusive evidence.

Objectives of this study will be: to determine the efficacy of honey or olive oil on the severity and pain of OM compared to placebo (standard care) and, (2) to assess which of the two interventions is more beneficial.

Research Questions:

1. Children/adults who receive honey (group 1) or olive oil (group 2) will have less severe OM compared to the control group (Severity is measured by recovery time from OM and is the primary outcome)
2. Children/adults who receive honey (group 1) OR Olive oil (group 2) will have less pain than the control group. (Severity of pain is the secondary outcome Methods: A randomized controlled study (RCT) will be used to evaluate the effect of topical application of honey or olive oil, in the treatment of chemotherapy-related OM in 60 participants with OM. The primary outcome will be the severity of mucositis, assessed by four trained nurses blinded to the study group using the scale presented by the World Health Organization (WHO). The secondary outcome will be pain also assessed by the four trained nurses on the visual analogue scale ort eh Wong Faces scale.

The relevance of this study lies in the possibility of challenging nurses in regard to the problem of OM and in proving a possible herbal cure that may influence clinical practice.

Data analysis: The characteristics of the three groups will be described using mean and SD, frequencies and percentages. Baseline differences between the two groups will be tested using ANOVA for continuous data, and the Chi-square for categorical data. Kruskall-Wallis (chi square) test will be used to find the association group assignment and WHO grades of OM and ANOVA and RANOVA tests will be used to find the association between group assignment and the pain scores. Bonferroni tests will be conducted to explore which of the three groups has the better outcomes.

Detailed description: When parents or adults express interest in the study they will be approached by the Principal investigator (LKB) or the 2 research nurses (RS or RA) who will make contact with the children and their parents and explain the study, ,answer all their questions and concerns and inform them about the study benefits/potential risks (see recruitment script appendix B in proposal). If a parent approves to participate in the study, he/she will sign an informed consent and any child above 7 will be asked to sign an assent form. The investigator will also assure the parents that participation is totally voluntary and it is not a part of the conventional treatment and that they have the full right to refuse participating and withdraw from the study at any time, even after signing the consent.

Recruitment activities will take when the children are hospitalized at the Children's cancer center in Lebanon (CCCL), 8 North and the Bone Marrow unit (BMT). Patients, parents and children will also have access to flyers in the unit briefly explaining the study. Potential subjects will be identified through reviewing daily census on the inpatient unit of CCCL, 8 north or the BMT unit. Participates will be screened for eligibility and will be excluded if they have any condition that may affect the efficacy of treatment as listed in the exclusion criteria. Participants will be randomly assigned to 1 of 3 groups, 20 patients in each group. The randomization method will be prepared in advance by a statistician not involved in the study, using a paper list-generated random assignment sequencel. Based on group assignment, participants will receive a different compound applied topically to the oral mucosa 3 times daily until healing, or for 7 days, whichever comes first.

Group 1 will receive 10cc of honey for adults and 5 cc for children, which will be supplied directly from a New Zealand.

Group 2 will receive maximum 5 g of extra virgin olive oil for adults and 2 cc for children directly from a local distributor in south Lebanon. It will be stored in dark containers at room temperature for use in the study.

Group 3 will serve as control, which at our institution is 5cc sodium bicarbonate, 5cc rinsidin and 5cc of mycostatin 4 times daily for children. For adults it is Caphosol in the BMT unit and in the Basile inpatient unit it is the magic solution (without xylocaine).

Groups 1 and 2 patients will be instructed to slowly rinse the honey or olive oil in their mouths, swish it around for 1 minute duration, so as to make the honey or oil in contact with the oral mucosa and slowly swallow so as to make better contact with the pharyngeal mucosa. For group 3, patients will swish the respective solution for 1 minute then spit it out. The order of the different solutions will be written in each medical record by the attending physician and the nurse will observe the patient taking the solution and will document the administration on the hospital flowsheet.

The independent variable for this study is either olive oil or honey The dependent variables will be primary and secondary:

1. The primary outcome will be the severity of OM measured by recovery time, defined as the number of days from the initiation of treatment until healing or day 7 assessed by four trained nurses on a daily basis and who are blinded to the study group using the scale presented by the World Health Organization (WHO). The WHO scale is based upon the ability to eat and drink combined with objective signs of mucositis, namely erythema and ulceration (7). Visualisation of the oral cavity is critical for scoring, as the presence of oral ulcers delineates a WHO mucositis grade which ranges from 0 to 4 where higher scores correspond to worse mucositis. The WHO scale is classified as follows: grade 0=normal, no mucositis; grade 1=soreness and erythema; grade 2=erythema, ulcer, can eat solids; grade 3=ulcers, require liquid diet only; grade 4=alimentation not possible. The PI will establish inte-rater reliability with the four nurses by assessing patients on the WHO scale. Each nurse will conduct the assessment and compare her/his results with the PI, this will be done until a reliability of \>. 80 is achieved. Reliability will be done before the study begins and then every month until the completion of the study.
2. The secondary outcome will be a pain assessed as per the institution's policy using the Visual analogue 10cm scale (VAS) or the Wong faces scale. A 0 indicates no mouth or throat pain and 10 indicates the most severe mouth or throat pain ( see appendix E in the proposal). The construct, convergent and predictive validity of the VAS and the Faces scales have been widely published (26). Pain scores of the oral mucosa will be conducted twice a daily for study purposes. The patients will be assessed by their RNs for pain which is documented in the patient charts twice per day in the morign and in the evening (even in the absence of pain).

Eligibility criteria: Inclusion Criteria:

The following are the inclusion criteria:

1. Children/Adults with leukemia (ALL, AML) receiving intensive (high dose) chemotherapy treatment such as myeloablative, doxorubicin or methotrexate during induction, consolidation and re-induction therapy.
2. Absence of any home remedy for mucositis
3. Patients with grades 1-3 OM based on the WHO grading system.

Exclusion Criteria:

1. Patients under non- intensive chemotherapeutic treatment.
2. Presence of advanced or severe periodontitis (patients with periodontal pockets of 6mm or more).
3. Patients with a cognitive disability which my no enable them to assess their pain
4. History of allergy to honey or olive oil.

Primary outcomes:
measure: The severity of Oral mucositis
timeFrame: 7 days or until healing or Discharge
Secondary outcomes:
measure: Pain as reported by children
timeFrame: 7 days or until healing or Discharge
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: American Univeristy of Beirut Medical Center
Study officials:
References:
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citation: Abdulrhman M, Elbarbary NS, Ahmed Amin D, Saeid Ebrahim R. Honey and a mixture of honey, beeswax, and olive oil-propolis extract in treatment of chemotherapy-induced oral mucositis: a randomized controlled pilot study. Pediatr Hematol Oncol. 2012 Apr;29(3):285-92. doi: 10.3109/08880018.2012.669026.
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