Condition category
Oral Health
Date applied
30/06/2020
Date assigned
15/07/2020
Last edited
15/07/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Background and study aims
Recurrent aphthous stomatitis (RAS) are common mouth ulcers. The cause of these ulcers are not always well understood, so treatment is mostly to treat the symptoms of the ulcer, to relieve pain and inflammation, and to accelerate the healing process. Medications applied directly to the ulcer have already been proved to be effective, however, more studies are needed to investigate the effectiveness of hyaluronic acid in the treatment of RAS to relieve pain and promote healing.

Most patients have their first experience of RAS between the ages of 10 and 19 years old and this may become less frequent with increasing age. Ulcers can heal spontaneously after one or two weeks but can then reoccur, this could be monthly or a few times per year.

The aim of this study is to assess the efficacy of hyaluronic-acid-based oral gel (Bexident® gel) in pain relief and ulcer healing.

Who can participate?
Candidates aged 12 to 50 years old can participate. Participants must have a current complaint of an oral ulcer (sore) that is causing pain. It's also important to not have used any other medication to treat the oral sores in the previous 48 hours, nor to suffer from other diseases that could give rise to oral sores.

What does the study involve?
Participants will be randomly allocated to relieve either the hyaluronic-acid-based oral gel (Bexident® gel), or a similar gel without hyaluronic acid. Participants will be asked to apply a gel on the sore for seven days and record the level of pain after each application according to certain instructions that will be given by the operators.

What are the possible benefits and risks of participating?
A possible benefit of using the oral gel is faster healing and pain relief. Currently, there are no known risks for the use of the oral gel.

Where is the study run from?
The Department of Biomedical, Surgical and Dental Sciences, University of Milan (Italy).

When is the study starting and how long is it expected to run for?
From November 2018 to January 2019

Who is funding the study?
The University of Milan (Italy) and BMG Pharma (Italy)

Who is the main contact?
Prof. Chiara Occhipinti
Chiara.Occhipinti@unimi.it

Trial website

Contact information

Type

Scientific

Primary contact

Prof Chiara Occhipinti

ORCID ID

Contact details

Via della Commenda 10
Milan
20122
Italy
+393339155689
Chiara.Occhipinti@unimi.it

Type

Public

Additional contact

Dr Maggie Stephen F. Fahim

ORCID ID

Contact details

Via della Commenda 10
Milan
20122
Italy
+39 3491194721
maggiesteven00@hotmail.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

SKT_MagF_GMT.250620

Study information

Scientific title

The efficacy of a topical gel containing hyaluronic acid in the treatment of minor recurrent aphthous ulcers in an Italian cohort: a randomized, double-blind, placebo-controlled clinical trial

Acronym

Study hypothesis

The aim of this randomized double-blind placebo-controlled clinical trial (RCT) is to evaluate the efficacy of a Hyaluronic Acid gel for the treatment of Recurrent Aphthous Stomata in an Italian cohort.

Ethics approval

Approved 19/09/2018, the Ethical Committee of the University of Milan (Via Festa del Perdono 7, 20122, Milan, Italy; +39 (0)2503111; comitato.etico@unimi.it), ref: 44/18

Study design

Randomized double-blind placebo-controlled parallel clinical trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Recurrent aphthous stomatitis

Intervention

70 patients with the complaint of RAS will be enrolled in this study, and will be randomly be assigned to the Test or the Placebo group in an equal ratio (1:1, 35 subjects in each group). The Test group is treated with Bexident® gel (Bexident Aftas Gel®, Barcelona, ISDIN). The medicated product contains polyvinylpyrrolidone (PVP), sodium hyaluronate and a few natural extracts. For preparation of the placebo gel, all previous ingredients are used except for PVP and sodium hyaluronate. Both formulations are packed in the same kind of tubes containing 8 ml of product.

An investigator not involved in clinical examination randomly divides and assigns a numerical code to each tube. Then the codes are assigned to patients by means of a computer-generated number list and the tubes are then given to the clinical investigators who are blind to the treatment agents contained inside.

All patients and clinical investigators are blinded to the group assignment and to the products contained in the assigned product. All the participants are clinically examined to measure the size of each ulcer at baseline, the examinations are done by the same unique investigator on all occasions (CO).

A periodontal probe are used to measure the distance between two opposite outer edges of the white margin of the ulcer. Two measurements perpendicular to each other passing through the center of the lesion are obtained and then multiplied to calculate the cross-sectional area of the ulcer. If the patient showed more than one ulcer, only the greatest one is recorded.

A visual analog scale (VAS) consisting of a 10 cm horizontal line ranking from 0 (no pain) to 10 (unbearable pain) is used for patients to self-assess their pain.

Patients are instructed, to squeeze approximately 1 milliliter of the product on a finger or a cotton tip three times a day for one week and to gently rub it on each lesion. It is recommended to refrain from eating or drinking for 60 minutes after application. For each lesion, a total amount of at least 21 ml of product is used. On the VAS scale, the patients areinstructed to mark the pain level every day before, right after, 20 and 60 minutes after drug application, from the first till the seventh day, for a total of 84 measurements for each patient.

The efficacy indices (EI) for ulcer pain are calculated at each time-point using the following formula: EI=[(Vx-V1) ÷V1] ×100%; with Vx referring to values measured within a particular time frame (in this study, at 2-7 days) and V0 referring to the baseline value to be measured at the first measurement (before the first application) on day 0. Efficacy indices (EI) are evaluated on a 4-rank scale: 1: healed, EI ≥95%; 2: marked improvement, EI ≥70% to <95%; 3: moderate improvement, EI ≥30% to <70%; 4: no improvement, EI <30%. Patients are considered to have shown marked improvement rate (MIR) when EI was ≥ 70% and improvement rate (IR) when EI was ≥ 30% (34).

Patients are also asked to report every day any adverse effects and to not use any other products for the treatment of aphthous ulcers while participating in the study or to report it (and in that case, they would be excluded from the study). The used questionnaire was dichotomic yes/no. In case of positive answer, it is asked to describe what they have experienced.

The data are then analyzed by a third operator, who is blinded to the study and does not perform any treatment on the patients. Compliance is not assessed because the total product provided to each patient was just sufficient for the designated dose and time frame of treatment.

Intervention type

Drug

Phase

Phase III

Drug names

Bexident® gel (Bexident Aftas Gel®, Barcelona, ISDIN)

Primary outcome measure

Pain is measured using a visual analogue scale (VAS) at baseline, then before, right after, 20 and 60 min after drug application, three times daily, for seven days (a total of 84 measurements for each patient)

Secondary outcome measures

Change in ulcer size is measured using a periodontal probe, two measurements of the distance between the two opposite outer edges of the white margin of the ulcer perpendicular to each other passing through the center of the lesion will be obtained and then multiplied to calculate the cross-sectional area of the ulcer, at baseline, then every 24 h for 7 days

Overall trial start date

01/10/2018

Overall trial end date

30/01/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged between 12 and 50 years
2. Presence of at least one aphthous ulcer in an easily accessible area of the mouth and reporting pain

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

70

Total final enrolment

70

Participant exclusion criteria

1. Pregnancy and lactation
2. Systemic disease such as Crohn’s disease, Behçet’s syndrome or ulcerative colitis
3. HIV, hepatitis C, or other systemic, acute or chronic infections
4. Use of other medications or drugs within 2 months, and specifically use of any local treatment for ulcers within 48 h of the start of the study

Recruitment start date

22/10/2018

Recruitment end date

21/12/2018

Locations

Countries of recruitment

Italy

Trial participating centre

University of Milan
Via della Commenda 10 Department of Surgical, Biomedical and Dental Sciences Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
20122
Italy

Sponsor information

Organisation

University of Milan

Sponsor details

Via della Commenda 10
Milan
20122
Italy
+393339155689
giampietro.farronato@unimi.it

Sponsor type

University/education

Website

http://www.unimi.it/ENG/

Funders

Funder type

Industry

Funder name

BMG Pharma

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Università degli Studi di Milano

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The datasets generated and/or analysed during the current study will be included in the subsequent results publication.

Intention to publish date

01/11/2020

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/07/2020: Trial’s existence confirmed by the Ethical Committee of the University of Milan.