Participants, materials and Study design:
This pilot study being a part of an ongoing randomized controlled clinical trial (ClinicalTrials.gov (NCT04336488)), was conducted on 12 patients suffering from erosive OLP. Ethical approval was obtained from the ethics research committee at the Faculty of Dentistry, Alexandria University, Egypt (IRB 00010556) -(IORG 0008839). The study was performed in accordance with the modified Declaration of Helsinki’s code for human clinical studies (2013). Informed consent was obtained from all participants after explaining the details of the study protocol.
Patients were recruited from the outpatient clinic of the Oral Medicine, Periodontology, Diagnosis, and Radiology Department, Faculty of Dentistry, Alexandria University, Egypt, during the period between December 2019 and January 2020.
The following inclusion criteria were applied: Patients with an age not less than 25 years, who were diagnosed with erosive OLP based on clinical examination and histopathological confirmation following the modified WHO criteria (2003) for the diagnosis of OLP(14). All patients had to be symptomatic and suffering from pain. Patients who were under anticoagulant medications, suffering from any systemic diseases or having any physical or mental abnormality, pregnant and lactating women, smokers, were excluded.
Intervention and measurements:
After detailed medical history taking, clinical examination, and biopsy taking, the Control group, comprised of 6 patients, was prescribed the treatment regimen of topical corticosteroid (triamcinolone acetonide 0.1% oral gel “Kenacort‐A‐Orabase)1 and topical anti-fungal agent (Miconaz oral gel)2,three times per day for 4 weeks. The test group included 6 patients given MMPs neutralizing agent (vaccinium macrocarp extract and vaccinium mytillus, Orochem spray 20ml)3, three times per day for 4 weeks.(15)
Clinical changes from baseline were evaluated at 2 time points: 1week and 4 weeks after commencement of the treatment, using the two following measurements as primary and secondary outcomes;
1- Subjective pain and discomfort severity were recorded using the Numeric Rating Scale (NRS) (16), categorized to (No pain (NRS 0), Mild pain (NRS 1-3), Moderate pain (NRS 4-7), Unbearable pain (NRS 8-10)). Patients were asked to assign a numerical score on the scale verbally to rate their pain intensity and the number was recorded.(17, 18)
2- Objective disease severity using (19) Thongprasom scoring system (this scoring system was selected despite the availability of more valid scoring systems to allow comparison of the results with those of other clinical trials as it is the most commonly used to date)(20) , categorized to; score 5 was assigned to a lesion of white striae with erosive areas >1 cm2, score 4 assigned to a lesion of white striae and erosive areas <1 cm2, score 3 assigned to a lesion of white striae and atrophic areas >1 cm2, score 2 assigned to a lesion of white striae and atrophic areas <1 cm2, score 1 assigned to a lesion having only white striae, and score 0 assigned to normal mucosa. Photographical records of the lesions were taken at baseline, after 1, and 4 weeks.
Randomization, blinding and allocation concealment
Patients were randomized after providing informed consent either into a test group or control by unpredictable random sequence using simple randomization procedures (computerized random numbers). Additionally, patients were blinded as to which group they were assigned. The allocation list was concealed by sequentially numbered, opaque, sealed envelopes.
Sample size estimation
For the original randomized clinical trial, A sample size of 18 patients per group (number of group = 2) (total sample size = 36 patients) is the enough required sample to detect a standardized effect size of 0.6150 (minimum difference in mean pain scores using NRS) change in primary outcome(21, 22), as statistically significant with 80% power and at a significance level of 95% (accepted α of 0.05).
Sample size was increased to 40 to control for attrition bias.(23) The sample size was calculated using GPower version 188.8.131.52.(24) Thirty percent (12/40 patients) of the original sample size was considered suitable to conduct this pilot study (n=12, 6 patients per group).
Differences in NRS and disease severity scores were compared using Mann Whitney U test. Whereas, changes across time were assessed using Friedman test. P value was adjusted for multiplicity by multiplying the uncorrected p-value by the number of comparisons made to set a significance level at 0.05.(25) Data were analyzed using IBM SPSS software package version 25.0. (Armonk, NY: IBM Corp)