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Topical "Non-Aromatic Very Rich in Steranes" (NAVS) Naphthalan for the Treatment of Oral Mucosal Diseases

Primary Purpose

Oral Lichen Planus, Recurrent Aphthous Stomatitis

Status
Completed
Phase
Phase 2
Locations
Croatia
Study Type
Interventional
Intervention
NAVS Naphthalan
0.05% Betamethasone dipropionate
Sponsored by
Ivan Alajbeg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Lichen Planus focused on measuring NAVS Naphthalan, Betamethasone dipropionate, Topical treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • for OLP patients: adult patients with a clinically and histologically proven OLP (Al-Hashimi et al, 2007)
  • for RAS patients: in the acute stage of the disease, according to Lehner (1968), at least 2 episodes per year

Exclusion Criteria:

  • for OLP patients: younger than 18 years, hepatobiliary system diseases, lichenoid reaction (amalgam, drugs) or lichen planus with lesions in contact to restorative materials (Zakrzewska et al, 2005), the current comparative systemic or local anti-inflammatory treatment (antibiotics, corticosteroids, non-steroidal antirheumatic drugs, chemotherapeutics) (Lo Muzio et al, 2001; Nolan et al, 2006; Rodriguez et al, 2007) and pregnancy.
  • for RAS patients: patients younger than 18 years, haematological deficits (assessed by complete blood count (CBC), iron (Fe), vitamin B12, hypersensitivity to toothpaste and oral mouth rinse solutions (assessed by medical history) (Nolan et al, 2006), pregnancy, inflammatory bowel disease (assessed by medical history), significant immunodeficiencies, current comparative systemic or topical anti-inflammatory treatment (antibiotics, corticosteroids, nonsteroidal antirheumatics, chemotherapeutics) (Lo Muzio et al, 2001; Nolan et al, 2006; Rodriguez et al, 2007).

Sites / Locations

  • School of Dental medicine, University of Zagreb

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

NAVS Naphthalan

0.05% Betamethasone dipropionate

Arm Description

NAVS oil in adhesive powder in a volume ratio 2:1, to apply on the affected mucosa three times daily during 4 weeks for OLP patients; NAVS oil in adhesive powder in a volume ratio 2:1, to apply on the affected mucosa three times daily during 5 days for RAS patients

0.05% Betamethasone dipropionate in adhesive powder in a volume ratio 1:1, to apply on the affected mucosa three times daily during 4 weeks for OLP patients; 0.05% Betamethasone dipropionate in adhesive powder in a volume ratio 1:1, to apply on the affected mucosa three times daily during 5 days for RAS patients

Outcomes

Primary Outcome Measures

The change of presence of reticulation, erythema and ulceration on mucosal surfaces
Clinical improvement of OLP lesions after treatment will be scored (Pibooniyom et al.,2005). This clinical scale measures the presence of reticular, erythematous and ulcerative lesions on oral mucosal surfaces, providing a score by adding those values. Investigator will assess patients' lesions on oral mucosal surfaces, on day 0 and day 28 and provide score for each assessment. The change of this score between the two time points is a measure of clinical efficacy of applied treatment modality. Calibration process : three examiners independently reviewed and evaluated photo of the individual patient. The second evaluation of photographs was a week after to assess the objectivity of the reading on the first visit. Once the examiners reviewed the photographs twice with one-week gap, the obtained results were analysed using Spearman "rank" correlation to determine intra- and inter-observer reliability.
The change in the number of RAS lesions
The number of RAS lesions will be recorded on day 0 and on day 5 after the start of treatment (Khandwala et al, 1997). The change in the number of lesions between the two time points is a measure of clinical efficacy of applied treatment modality.
The change in the diameter of RAS lesions
The change in the diameter of RAS lesions (in millimeters) will be recorded on day 0 and on day 5 after the start of treatment (Khandwala et al, 1997). The change in the cumulative diameter of lesions between the two time points is a measure of clinical efficacy of applied treatment modality.
The change of pain intensity and discomfort in OLP patients
The intensity of pain and discomfort will be determined using a 100 mm visual analog scale (VAS) on day 0 and day 28. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
The quality of life change in OLP patients
The quality of life for OLP patients will be determined using "Oral health impact profile"(OHIP-14) questionnaire on day 0 and day 28. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
The change of pain intensity and discomfort in RAS patients
The intensity of pain and discomfort will be determined using a 100 mm visual analog scale (VAS) 30 and 60 minutes after the application of the therapeutic agent at home. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
The quality of life change in RAS patients
The quality of life for RAS patients will be determined using "Oral health impact profile"(OHIP-14) questionnaire on day 0 and day 5. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.

Secondary Outcome Measures

Adverse reactions to treatment modalities in OLP patients
In OLP patients application of both treatment modalities lasts for 28 days. The occurrence of oral Candidal infection or irritation will be recorded by clinician on day 28. The frequency of each will be compared between two treatment groups.

Full Information

First Posted
June 8, 2016
Last Updated
September 29, 2016
Sponsor
Ivan Alajbeg
Collaborators
Ministry of Science, Education and Sport, Republic of Croatia
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1. Study Identification

Unique Protocol Identification Number
NCT02920658
Brief Title
Topical "Non-Aromatic Very Rich in Steranes" (NAVS) Naphthalan for the Treatment of Oral Mucosal Diseases
Official Title
Nonaromatic Naphthalan - Composition Study and Biological Effects on Epithelial Tissues
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ivan Alajbeg
Collaborators
Ministry of Science, Education and Sport, Republic of Croatia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study evaluates the effectiveness of topical NAVS naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Half of participants with OLP and RAS will receive topical NAVS naphthalan in adhesive paste, while the other half will receive 0.05%-betamethasone dipropionate in adhesive paste. Our hypothesis is that NAVS could be efficient in the treatment of OLP and RAS, with effects comparable to that of topical steroids.
Detailed Description
Non-Aromatic-Very rich in Steranes (NAVS) naphthalan is a transparent, earth mineral oil prepared by a complex set of procedures of separations and refining, starting with a special oil that is used as the raw material for brown naphthalane, which has been successfully used in the treatment of psoriasis. In order to remove potentially mutagenic polycyclic aromatic hydrocarbons (PAHs), liquid chromatography was used. UV / VIS (ultra violet / visible light) spectrophotometry confirmed that PAHs were bellow detection threshold. Additionally, the precise distillation process has concentrated steranes, which are important bioactive constituents. Since steranes contain similar chemical structure as well-known bioactive substances, such as vitamin D3 and steroid hormones, the assumption is that NAVS is effective in the treatment of oral diseases which have immune genesis such as OLP and RAS. Today, topical steroid preparations are considered as first-line therapy for many chronic immune-mediated inflammatory diseases of the oral mucosa. Risks of short-term use of topical corticosteroids are clinically insignificant, while their long-term use is not recommended because of potential side effects, such as mucosal atrophy, secondary infection with Candida albicans, possible systemic absorption and suppression of the adrenal gland. Study participants are adult patients of the Department of Oral Medicine, School of Dental Medicine in Zagreb, with a clinically and histologically proven OLP or RAS in the acute stage of the disease.The treatment outcome of the OLP patients will be measured by clinical improvement and subjective symptomatic relief. The outcome of RAS patients treated by NAVS naphthalan or by betamethasone will be measured clinically by the decrease in number and size of lesions as well as by subjective symptomatic relief over treatment period. One member of the team, who will not evaluate the therapeutic effect, will took care of the allocation of test and control preparations. At the end of the study, a randomization code will be opened and statistically analysed. In both clinical and subjective domains, of both clinical conditions, the improvement rate will be measured by comparing these readings, as the percentual reduction of clinical scores and symptoms. Since the data will not be normally distributed, methods of nonparametric statistics will be used: Wilcoxon test for dependent and Mann-Withney test for independent samples. Baseline intergroup differences will be assessed by Mann-Withney test. For the interpretation of the average values, medians and interquartile ranges (IQR) will be used. Fisher exact test will be used to compare gender representation among the groups. Statistical analysis will be performed using MedCalc Software 13.0.0.0 (Acacialaan 22, 8400 Ostend, Belgium). P value lower then 0.05 (p< 0.05) will be considered statistically significant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Lichen Planus, Recurrent Aphthous Stomatitis
Keywords
NAVS Naphthalan, Betamethasone dipropionate, Topical treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NAVS Naphthalan
Arm Type
Experimental
Arm Description
NAVS oil in adhesive powder in a volume ratio 2:1, to apply on the affected mucosa three times daily during 4 weeks for OLP patients; NAVS oil in adhesive powder in a volume ratio 2:1, to apply on the affected mucosa three times daily during 5 days for RAS patients
Arm Title
0.05% Betamethasone dipropionate
Arm Type
Active Comparator
Arm Description
0.05% Betamethasone dipropionate in adhesive powder in a volume ratio 1:1, to apply on the affected mucosa three times daily during 4 weeks for OLP patients; 0.05% Betamethasone dipropionate in adhesive powder in a volume ratio 1:1, to apply on the affected mucosa three times daily during 5 days for RAS patients
Intervention Type
Drug
Intervention Name(s)
NAVS Naphthalan
Intervention Type
Drug
Intervention Name(s)
0.05% Betamethasone dipropionate
Other Intervention Name(s)
Beloderm
Primary Outcome Measure Information:
Title
The change of presence of reticulation, erythema and ulceration on mucosal surfaces
Description
Clinical improvement of OLP lesions after treatment will be scored (Pibooniyom et al.,2005). This clinical scale measures the presence of reticular, erythematous and ulcerative lesions on oral mucosal surfaces, providing a score by adding those values. Investigator will assess patients' lesions on oral mucosal surfaces, on day 0 and day 28 and provide score for each assessment. The change of this score between the two time points is a measure of clinical efficacy of applied treatment modality. Calibration process : three examiners independently reviewed and evaluated photo of the individual patient. The second evaluation of photographs was a week after to assess the objectivity of the reading on the first visit. Once the examiners reviewed the photographs twice with one-week gap, the obtained results were analysed using Spearman "rank" correlation to determine intra- and inter-observer reliability.
Time Frame
28 days per patient
Title
The change in the number of RAS lesions
Description
The number of RAS lesions will be recorded on day 0 and on day 5 after the start of treatment (Khandwala et al, 1997). The change in the number of lesions between the two time points is a measure of clinical efficacy of applied treatment modality.
Time Frame
5 days per patient
Title
The change in the diameter of RAS lesions
Description
The change in the diameter of RAS lesions (in millimeters) will be recorded on day 0 and on day 5 after the start of treatment (Khandwala et al, 1997). The change in the cumulative diameter of lesions between the two time points is a measure of clinical efficacy of applied treatment modality.
Time Frame
5 days per patient
Title
The change of pain intensity and discomfort in OLP patients
Description
The intensity of pain and discomfort will be determined using a 100 mm visual analog scale (VAS) on day 0 and day 28. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
Time Frame
28 days per patient
Title
The quality of life change in OLP patients
Description
The quality of life for OLP patients will be determined using "Oral health impact profile"(OHIP-14) questionnaire on day 0 and day 28. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
Time Frame
28 days per patient
Title
The change of pain intensity and discomfort in RAS patients
Description
The intensity of pain and discomfort will be determined using a 100 mm visual analog scale (VAS) 30 and 60 minutes after the application of the therapeutic agent at home. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
Time Frame
5 days per patient
Title
The quality of life change in RAS patients
Description
The quality of life for RAS patients will be determined using "Oral health impact profile"(OHIP-14) questionnaire on day 0 and day 5. The change in the amount between the two time points is a measure of clinical efficacy of applied treatment modality.
Time Frame
5 days per patient
Secondary Outcome Measure Information:
Title
Adverse reactions to treatment modalities in OLP patients
Description
In OLP patients application of both treatment modalities lasts for 28 days. The occurrence of oral Candidal infection or irritation will be recorded by clinician on day 28. The frequency of each will be compared between two treatment groups.
Time Frame
28 days per patient

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: for OLP patients: adult patients with a clinically and histologically proven OLP (Al-Hashimi et al, 2007) for RAS patients: in the acute stage of the disease, according to Lehner (1968), at least 2 episodes per year Exclusion Criteria: for OLP patients: younger than 18 years, hepatobiliary system diseases, lichenoid reaction (amalgam, drugs) or lichen planus with lesions in contact to restorative materials (Zakrzewska et al, 2005), the current comparative systemic or local anti-inflammatory treatment (antibiotics, corticosteroids, non-steroidal antirheumatic drugs, chemotherapeutics) (Lo Muzio et al, 2001; Nolan et al, 2006; Rodriguez et al, 2007) and pregnancy. for RAS patients: patients younger than 18 years, haematological deficits (assessed by complete blood count (CBC), iron (Fe), vitamin B12, hypersensitivity to toothpaste and oral mouth rinse solutions (assessed by medical history) (Nolan et al, 2006), pregnancy, inflammatory bowel disease (assessed by medical history), significant immunodeficiencies, current comparative systemic or topical anti-inflammatory treatment (antibiotics, corticosteroids, nonsteroidal antirheumatics, chemotherapeutics) (Lo Muzio et al, 2001; Nolan et al, 2006; Rodriguez et al, 2007).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ivan Alajbeg, PhD
Organizational Affiliation
University of Zagreb School of Dental Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
School of Dental medicine, University of Zagreb
City
Zagreb
ZIP/Postal Code
10 000
Country
Croatia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Yes, de-identified data are available upon request.
Citations:
PubMed Identifier
17261375
Citation
Al-Hashimi I, Schifter M, Lockhart PB, Wray D, Brennan M, Migliorati CA, Axell T, Bruce AJ, Carpenter W, Eisenberg E, Epstein JB, Holmstrup P, Jontell M, Lozada-Nur F, Nair R, Silverman B, Thongprasom K, Thornhill M, Warnakulasuriya S, van der Waal I. Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103 Suppl:S25.e1-12. doi: 10.1016/j.tripleo.2006.11.001. Epub 2007 Jan 29.
Results Reference
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PubMed Identifier
9117754
Citation
Khandwala A, Van Inwegen RG, Alfano MC. 5% amlexanox oral paste, a new treatment for recurrent minor aphthous ulcers: I. Clinical demonstration of acceleration of healing and resolution of pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Feb;83(2):222-30. doi: 10.1016/s1079-2104(97)90009-3.
Results Reference
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PubMed Identifier
4297643
Citation
Lehner T. Autoimmunity in oral diseases, with special reference to recurrent oral ulceration. Proc R Soc Med. 1968 May;61(5):515-24. No abstract available.
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PubMed Identifier
11722711
Citation
Lo Muzio L, della Valle A, Mignogna MD, Pannone G, Bucci P, Bucci E, Sciubba J. The treatment of oral aphthous ulceration or erosive lichen planus with topical clobetasol propionate in three preparations: a clinical and pilot study on 54 patients. J Oral Pathol Med. 2001 Nov;30(10):611-7. doi: 10.1034/j.1600-0714.2001.301006.x.
Results Reference
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PubMed Identifier
11695759
Citation
Neppelberg E, Johannessen AC, Jonsson R. Apoptosis in oral lichen planus. Eur J Oral Sci. 2001 Oct;109(5):361-4. doi: 10.1034/j.1600-0722.2001.00081.x.
Results Reference
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PubMed Identifier
16918596
Citation
Nolan A, Baillie C, Badminton J, Rudralingham M, Seymour RA. The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med. 2006 Sep;35(8):461-5. doi: 10.1111/j.1600-0714.2006.00433.x.
Results Reference
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PubMed Identifier
15897856
Citation
Piboonniyom SO, Treister N, Pitiphat W, Woo SB. Scoring system for monitoring oral lichenoid lesions: a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Jun;99(6):696-703. doi: 10.1016/j.tripleo.2004.07.013.
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PubMed Identifier
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Citation
Rodriguez M, Rubio JA, Sanchez R. Effectiveness of two oral pastes for the treatment of recurrent aphthous stomatitis. Oral Dis. 2007 Sep;13(5):490-4. doi: 10.1111/j.1601-0825.2006.01327.x.
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Citation
Zakrzewska JM, Chan ES, Thornhill MH. A systematic review of placebo-controlled randomized clinical trials of treatments used in oral lichen planus. Br J Dermatol. 2005 Aug;153(2):336-41. doi: 10.1111/j.1365-2133.2005.06493.x.
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PubMed Identifier
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Citation
Rogulj AA, Z Alajbeg I, Brailo V, Skrinjar I, Zuzul I, Vucicevic-Boras V, Alajbeg I. Topical NAVS naphthalan for the treatment of oral lichen planus and recurrent aphthous stomatitis: A double blind, randomized, parallel group study. PLoS One. 2021 Apr 8;16(4):e0249862. doi: 10.1371/journal.pone.0249862. eCollection 2021.
Results Reference
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Topical "Non-Aromatic Very Rich in Steranes" (NAVS) Naphthalan for the Treatment of Oral Mucosal Diseases

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