Honey or Olive Oil for Treating Oral Mucositis in Children and Adults With Leukemia Receiving Intensive Chemotherapy
Honey or Olive Oil for Treating Oral Mucositis in Children and Adults With Leukemia Receiving Intensive Chemotherapy
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.
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).
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.