Reference ↗
Title	The Effect of Aloe Vera Solution on Chemotherapy-Induced Stomatitis in Clients with Lymphoma and Leukemia: A Randomized Controlled Clinical Trial
Topic	Aloe vera
Author	Mansouri, P, Haghighi, M, Beheshtipour, N, Ramzi, M
Year	2016
Journal	International Journal of Community Based Nursing and Midwifery
DOI	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876780/

Study Note

As with radiotherapy, many patients undergoing chemotherapy treatment also suffer from inflammation of the oral mucosa. In this study, researchers investigated the effect of an aloe mouthwash on the severity of oral mucosal inflammation and associated pain. Patients rinsed their mouths three times a day with either an aloe mouthwash or a standard mouthwash. After three days, patients who used the aloe mouthwash had a lower severity of stomatitis and less pain. This effect of the aloe mouthwash was also maintained after 14 days of use. An aloe mouthwash was therefore able to reduce the severity and pain of oral mucosal inflammation in patients undergoing chemotherapy.

Wie unter Strahlentherapie leiden auch viele Patienten unter Chemotherapie-Behandlung unter einer Mundschleimhautentzündung. In dieser Studie haben Forscher die Wirkung einer Aloe-Mundspülung auf die Schwere einer Mundschleimhautentzündung und damit assoziierte Schmerzen untersucht. Patienten haben ihren Mund dreimal täglich mit entweder eine Aloe-Mundspülung oder eine Standard-Mundspülung gespült. Nach drei Tagen hatten Patienten, die die Aloe-Mundspülung nutzten, einen niedrigeren Ausprägung der Stomatitis und weniger Schmerz. Dieser Effekt der Aloe-Mundspülung blieb auch nach 14 Tagen der Anwendung erhalten. Eine Aloe-Mundspülung konnte demnach die Schwere und den Schmerz der Mundschleimhautentzündung bei Patienten unter Chemotherapie reduzieren.

Brief summary

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Multicentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	?
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	No
Number of arms	2

Study characteristics

Inclusion criteria	Age > 18 years; acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL); being under chemotherapy
Exclusion criteria	Suffering from any other underlying diseases; being addicted to cigars, tobacco and opioid drugs; having a history of sensitivity to aloe vera; developing any kind of sensitivity to any material during the study; developing any acute condition during the study; and unwillingness to continue participation in the study
N randomized	64
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	ITT Analysis
Specifications on analyses	?
Countries of data collection	Iran
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T0: T1:

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	Curative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Hematologic Cancers - Leukemia (Acute Lymphocytic/Acute Myeloid/Chronic Lymphocytic/Chronic Myeloid)
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	NI
Specifications on cancer stages	Type of disease: Acute Myeloid Leukemia (AML): Control arm = 17 (26.6%); Aloe arm =10 (15.6%) Acute Lymphocytic Leukemia (ALL): Cobtrol arm = 15 (23.4%); Aloe arm = 22 (34.4%)
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	NI
Previous cancer therapies	NI
Gender	Mixed
Gender specifications	Gender per arm: Aloe arm: 19 (29.7%) male; 13 female (20.3%) Placebo arm: 19 (29.7%) male; female (20.3%)
Age groups	Adults (18+)
Age groups specification	Mean age (SD) per arm: Aloe arm: 46.25(18.17) years Placebo arm: 47.78(18.28) years

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	32
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	0
Drop-out reasons	NA
Intervention	Aloe vera mouthwash
Dosage and regime	Washing mouthes with 5ml of aloe vera mouthwash (Saline, Cholorhexidine, and Nystatine) for 2 minutes 3 times a day and avoid eating and drinking for 30 minutes after that for 2 weeks.
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	14
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	32
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	0
Drop-out reasons	NA
Intervention	Standard mouthwash
Dosage and regime	Washing mouthes with 5ml of standard mouthwash (Saline, Cholorhexidine, and Nystatine) for 2 minutes 3 times a day and avoid eating and drinking for 30 minutes after that for 2 weeks.
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	14
Side effects / Interactions	NI

Outcomes

<ul><li>"Stomatits" is not in the list (Anorexia/Cachexia, Anxiety, Appetite, Cerebral oedema, Cognitive functioning, Cognitive impairment, Depression, Dermatitis, Distress, Dysgeusia, ...) of allowed values for the "Outcome name" property.</li> <li>"WHO stomatitis intensity survey checklist" is not in the list (AQoL-8D (Assessment of Quality of Life), ASAT (Auditory Sustained Attention Test), BIA (Bioelectrical impedance analysis), BPI-SF (Brief Pain Inventory - Short Form), CTCAE (Common Terminology Criteria of Adverse Events), ESAS (Edmonton Symptom Assessment Scale), FAACT (Functional Assessment of Anorexia-Cachexia Therapy), FACIT (Functional Assessment of Chronic Illness Therapy), FLIE (Functional Living Index for Emesis), Genitourinary atrophy self-assessment tool, ...) of allowed values for the "Type of measurement" property.</li></ul>

Stomatitis

Outcome type As specificed by the authors	Primary
Outcome specification	The patients’ mouths were examined for stomatitis by two assistants on days 1, 3, 5, 7, and 14 with WHO stomatitis intensity survey checklist: 0 = no stomatitis 1 = represents pain and erythema without wounds 2 = refers to the case where wound and erythema exist, but the patient is able to eat solid food 3 = is existence of extensive wound and erythema and inability to eat solid food 4 = mucosal bleeding, extensive inflammation, and complete inability to eat and drink
Type of measurement	WHO-Scale (World Health Organisation)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Mean (SD) Stomatitis per arm: Day Control arm Aloe arm Day 1 0.312(0.592) 0.125(0.336) p=0.178 Day 3 1.406(0.559) 0.500(0.508) p=0.001 Day 5 1.843(0.447) 0.937(0.504) p=0.001 Day 7 2.000(0.439) 1.125(0.553) p=0.001 Day 14 0.593(0.498) 0.938(0.296) p=0.001
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant difference was found between the two arms with respect to the mean intensity of stomatitis and pain on day 1, but a significant difference was observed in this regard on days 3 to 14.

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Pain

Outcome type As specificed by the authors	Primary
Outcome specification	The patients were asked to report their pain intensity by VAS, a 10cm ruler in which zero shows no pain and 10 represents intolerable pain.
Type of measurement	VAS (Visual Analogue Scale)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Mean (SD) pain per arm: Day Control arm Aloe arm Day 1 0.156(0.627) 0.001(0.001) p=0.154 Day 3 1.812(1.424) 0.187(0.737) p=0.001 Day 5 3.468(1.480) 0.781(1.337) p=0.001 Day 7 4.000(1.502) 1.125(1.431) p=0.001 Day 14 0.812(1.148) 0.031(0.176) p=0.001
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant difference was found between the two arms with respect to the mean intensity of stomatitis and pain on day 1, but a significant difference was observed in this regard on days 3 to 14.

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Funding and Conflicts of Interest

Funding	Support from the Shiraz University of Medical Sciences
Conflicts of Interest	According to authors no conflict of interest

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis	?
- Reasons for insufficient sample size based on power analysis	?
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention	?
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing	?
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over	?
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?

Additional Notes

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