Reference ↗
Title	Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial
Topic	Aloe vera
Author	Sahebnasagh, A, Ghasemi, A, Akbari, J, Alipour, A, Lashkardoost, H, Ala, S, Salehifar, E
Year	2017
Journal	The Journal of Alternative and Complementary Medicine
DOI	https://doi.org/10.1089/acm.2017.0047

Study Note

Brief summary

A common side effect of radiotherapy to the pelvic area is inflammation of the rectum (proctitis). In this study, researchers tested the use of a rectal ointment containing 3% aloe to reduce rectal inflammation in patients undergoing radiotherapy for pelvic cancer. All patients who developed signs of rectal inflammation during their radiotherapy were divided into two arms. One arm received aloe ointment, the other arm a placebo ointment (without aloe). Patients were asked to apply their assigned ointment rectally twice daily for four weeks. Patients who used the aloe ointment had less diarrhoea, urge to defecate and overall symptoms of rectal inflammation than those who used the placebo ointment. The aloe ointment proved to be more effective in reducing the patients' symptoms and had no side effects.

Eine häufige Nebenwirkung der Bestrahlung im Beckenbereich ist die Entzündung des Enddarms (Proktitis). In dieser Studie testeten die Forscher die Verwendung einer Rektalsalbe mit 3% Aloe zur Verminderung der rektalen Entzündung bei Patienten, die sich einer Strahlentherapie wegen Krebs im Beckenbereich unterziehen. Alle Patienten, die während ihrer Strahlentherapie Anzeichen einer rektalen Entzündung entwickelten, wurden in zwei Gruppen eingeteilt: Aloe-Salbe oder eine Placebo-Salbe (ohne Aloe). Diese Patienten wurden gebeten, ihre zugeordnete Salbe vier Wochen lang zweimal täglich rektal anzuwenden. Patienten, die die Aloe-Salbe verwendeten, hatten weniger Durchfall, Stuhldrang und Gesamtsymptome einer rektalen Entzündung als diejenigen, die die Placebo-Salbe verwendeten. Die Aloe-Salbe erwies sich als wirksam zur Verringerung der Symptome der Patienten und hatte keine Nebenwirkungen aufgewiesen

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	?
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	Triple
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; cancer in the pelvic area, radiotherapy and acute proctitis (ARP)
Exclusion criteria	Active infection; other causes of haematochezia including bowel cancer; IBD; haemorrhoids; anal incontinence; anorectal fistula; anorectal stenosis; previous rectal surgery; pregnant or breastfeeding women; women of childbearing age without appropriate contraception; allergy to components of the ointments tested; use of antibiotics or steroids
N randomized	20
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	The specific analysis method is not stated in the study, however, according to the authors, all included patients were evaluated at the end of the study.
Countries of data collection	Iran
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T0: Baseline (week 1) T1: Week 2 T2: Week 3 T3: Week 4

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	Prostate Cancer, Gynecologic Cancers, Genitourinary Cancers - Bladder Cancer, Colorectal Cancer - Rectal Cancer
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	?
Comorbidities	NI
Current cancer therapies	Radiation therapy
Specifications on cancer therapies	The radiation dose was 50-70Gy (1.8-2Gy 5x per day)
Previous cancer therapies	?
Gender	Mixed
Gender specifications	All participants: female = 7 (35%); male = 13 (65%) Aloe arm: male = 5 (55.6%) Placebo arm: male = 8 (72.7%)
Age groups	Adults (18+)
Age groups specification	Median (range) of all participants = 57.6 (24-84) years Mean (SD) age per arm: Aloe arm = 55.7 (15.4) years Placebo arm = 58.7 (15.9) 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	9
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 ointment
Dosage and regime	1g Aloe ointment (3% aloe powder, 2.3% white paraffin, 94.7% Vaseline) rectally 2x daily for 4 weeks. + all patients: 500mg Sulfasalazine 4x per day + all patients: radiotherapy
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.	28
Side effects / Interactions	No adverse events were reported by the patients.

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	11
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	Placebo ointment
Dosage and regime	1g Placebo ointment (without aloe vera) rectally 2x daily for 4 weeks + all patients: 500mg Sulfasalazine 4x per day + all patients: radiotherapy
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.	28
Side effects / Interactions	No adverse events were reported by the patients

Outcomes

Toxicity

Outcome type As specificed by the authors	?
Outcome specification	Clinical presentation score Symptoms: Bleeding; Diahrroe; Fecal urgency; Abdominal/rectal pain Possibile score range: 0-16 Grade of scale: 0 = Not present 1 = Minor symptoms not requiring medications 2 = Moderate disturbing symptoms alleviated by analgesic or anticholineric medication 3 = Significant symptoms with bowel movement 4 = Significant discomfort on rest or symptoms requiring hospitalization
Type of measurement	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".	Clinical presentation score per arm: Mean (SD) The aloe arm had a decrease of symptoms from baseline = 4.3 (2.2) to week 4 = 1.2 (0.8). The placebo arm had a decrease of symptoms from baseline = 4.2 (1.2) to week 4 = 3.5 (1.1). The difference in the clinical presentation scroe between the arms was statistically significant (p=0.008). Significantly less diarrhoea (p=0.008) and fecal urgency (p=0.027) in the aloe arm compared to placebo arm.
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".	NA

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	?

Quality of life

Outcome type As specificed by the authors	Primary
Outcome specification	The effect of radiation-induced symptoms on lifestyle Grade 0 = Symptoms cause no effect on daily activity 1 = Symptoms cause inconveniences at least once a week 2 = Symptoms interfere with day-to-day activities more than once a week 3 = Symptoms interfere with routine activities on a daily basis 4 = Afraid to leave home with significant restriction in social life
Type of measurement	Unspecified questionnaire
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".	?
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".	NA

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	?

Mental status/ function

Outcome type As specificed by the authors	Primary
Outcome specification	Psychosocial status: The patients were requested to weekly fill out the HAD form considering their feelings during past week.
Type of measurement	HADS (Hospital Anxiety and Depression 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".	No difference between the arms.
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".	NA

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	?

Toxicity

Outcome type As specificed by the authors	Primary
Outcome specification	Diarrhoea, proctitis, cystitis Grades: 0 = No symptoms 1 = Minor symptomsrequiring no treatment 2 = Symptoms, that respond to simple outpatient management, and do not affect lifestyle 3 = Distressing symptoms affecting lifestyle; may necessitate hospital admissionor minor surgical intervention 4 = Major surgical intervention or long stay in the hospital necessary 5 = Fatal complications
Type of measurement	RTOG Acute Radiation Morbidity Scoring Criteria (Radiation Therapy Oncology Group)
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".	Significantly lower RTOG toxicity score (p=0.0016) in the aloe arm compared to placebo arm. Aloe arm: Baseline = 2.89 (2.1) to week 4 = 0.89 (1.0) Placebo arm: Baseline 3.64 (1.4) to week 4 = 3.09 (1.3)
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".	NA

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	?
Conflicts 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

?