## Protocol Section
### Identification Module
**NCT ID:** NCT06421038

**Brief Title:** Efficacy of Thyme Honey in The Management of Oral Aphthous Ulcers

**Official Title:** Efficacy of Thyme Honey in The Management of Oral Aphthous Ulcers: A Randomized Controlled Clinical Trial

#### Organization Study ID Info
**ID:** 24-031
#### Organization
**Class:** OTHER
**Full Name:** British University In Egypt
### Status Module
#### Completion Date
**Date:** 2024-05-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-05-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-10

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** British University In Egypt

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Recurrent aphthous stomatitis (RAS) is considered the most common oral mucosal lesion, present first in childhood or adolescence. Aphthous ulcers affect up to 25% of the general population, and 3-month recurrence rates are as high as 50%, it is more common in female, also it increases by increasing age and minor aphthous ulcers are 80% of suffered patient.

Due to the antimicrobial, anti-inflammatory, antifungal, and analgesic effects of Thyme honey, and the lack of evidence in the considered population, the present study aimed to assess the effect of honey on the pain relief in patients with minor RAU as a primary objective and to assess the healing effect of natural thyme honey on minor RAU, and the Oral Health Impact Profile (OHIP-14) as a secondary objectives.

**Detailed Description:** Treatment of aphthous will usually be for three purposes: reduction of pain and inflammation, prevention of secondary infection, reduction of duration and repetition of aphthous. The most common treatments, after oral hygiene, are: use of local and oral steroids that have effect on T-lymphocytes and reduce inflammation, use of local antibiotics, for example, chlorohexidine, benzidamine, solving vitamin and mineral deficiency, such as B12, iron, folic acid, and avoidance of food allergens. Other treatments such as amelexanox, a potent inhibitor of inflammation due to mast cells and neutrophils. levamisol, talidomide are effective too.

Many factors may be involved in its progression, such as genetic predisposition, immunological abnormalities, microbial infection, psychological stress, and hormonal state. Since the etiology and pathogenesis of RAS remains unclear, there is currently no consensus regarding a definitive curative therapy. The commonly accepted treatment strategy is to lessen the pain and duration of lesions. Topical corticosteroids, antibiotics, and analgesics are highly recommended for patients with RAS.

However, longer treatment and frequent exposure to these medications may cause fungal infection and drug resistance, which may further lead to more severe adverse effects or even life-threatening complications. Natural herbal medicines as an alternative therapy for RAS have been widely used in many countries for decade. Clinical studies on the use of such remedies have reported favorable benefits to patients by reducing the discomfort and duration of ulcers.

The large volume of literatures reported the effectiveness of honey. It indicates that it may potentially be useful to treat periodontal diseases, mouth ulcers and other problems of oral health. Furthermore, the application of honey to a wound has been demonstrated to stimulate the production and release of pro-inflammatory cytokines that assist in the wound healing process, such as interleukin-1 and tumor necrosis factor-alpha. The topical application of honey to various injured tissues has also been shown to stimulate wound repair through the stimulation of growth of epithelial cells, reduction of edema, and wound debridement.

Takzaree et al in 2017 have evaluated the effects of local application of thyme honey in open cutaneous wound healing and concluded that local application of honey two times per day could boost the healing process as it reduces the inflammation, increases granulation tissue formation, and promotes angiogenesis and epithelialization, and this would eventually result in a quicker wound healing process. These antioxidants and wound healing effects have also been validated for Tulkarm honey and Thymus vulgaris honey. A recent study revealed substantial beneficial effects of Thymus vulgaris honey on skin wound healing and recommended its use in various types of wounds.

Recent research aimed to evaluate the effect of thyme honey oral gel in the prevention of chemotherapy-induced oral mucositis in patients with breast cancer with an emphasis on patient-reported symptoms. The study concluded that the use of thyme honey oral gel reduced the incidence, duration, and severity of symptoms of oral mucositis, in addition to delaying the occurrence of grade ≥2 oral mucositis.

### Conditions Module

**Conditions:**

- Aphthous Stomatitis (Major) (Minor)

- Treatment Compliance

**Keywords:**

- Oral diseases

- Thyme honey

- anti-inflammatory

- natural products

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Thyme honey on recurrent aphthous stomatitis

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** the care provider and the outcomes assessor will not know which treatment will be given to the patients.

**Who Masked:**

- CARE_PROVIDER

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 10 patients will be treated by thyme honey application (100% pure natural honey, applied by themselves) on their ulcers three times a day for 7 days.

**Intervention Names:**

- Other: Thyme honey

**Label:** Thyme honey

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 10 patients will be treated by kenalog in orabase (Triamcinolone acetonide 0.1% in oral paste 5g), three times a day for 7 days only.

**Intervention Names:**

- Drug: Kenalog

**Label:** kenalog in orabase

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Thyme honey

**Description:** Thyme honey is a rich monofloral honey variety formed by bees that collect nectar from thymus vulgaris flowers. thyme honey application (100% pure natural honey, applied by themselves) on their ulcers three times a day for 7 days

**Name:** Thyme honey

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- kenalog in orabase

**Description:** kenalog in orabase (Triamcinolone acetonide 0.1% in oral paste 5g)

**Name:** Kenalog

**Other Names:**

- kenalog in orabase

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Visual Analog Scale (0-10) will be used to determine the intensity of pain on day 0, day 3, day 5, and day 7.

**Measure:** Pain intensity

**Time Frame:** 7 days.

#### Secondary Outcomes

**Description:** after starting treatment, ulcer size will be recorded on day 0, day 3, day 5, and day 7, using a calibrated dental probe with millimeter marking.

**Measure:** Size of ulcers (in mm)

**Time Frame:** 7 days.

**Description:** The Oral Health Impact Profile (OHIP-14) questionnaire has been assessed 1 week after intervention. OHIP-14 utilizes a scale with five categories (1 = never, 2 = hardly ever, 3 = occasionally, 4 = fairly often, and 5 = very often). A lower score in any of the five categories indicates higher satisfaction

**Measure:** The Oral Health Impact Profile (OHIP-14) questionnaire

**Time Frame:** 7 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* • The study involved patients who had a positive history of having similar oral mucosal ulcers for 3-4 months and ulcers for \<48 h.

  * Clinically diagnosed patients with chronic aphthous stomatitis measuring ≤5 mm in size in the oral cavity and who gave written consent for participation.
  * Only single ulcers were considered for the study.
  * Systemically health patients.

Exclusion Criteria:

* The study excluded patients with a history of associated systemic disease.

  * Cases of chronic aphthous stomatitis (major), lesions of herpetic form, numerous RAS lesions, and smoking.
  * In addition, no consideration was given to patients with a history of hypersensitivity to honey.

**Minimum Age:** 19 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Dalia.ghalwash@bue.edu.eg

**Name:** Dalia Ghalwash, Phd

**Phone:** 01005120159

**Role:** CONTACT

**Contact 2:**

**Email:** asmaa.aboubakr@bue.edu.eg

**Name:** Asmaa A Ras, Phd

**Phone:** 01098015060

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cairo

**Contacts:**

***Contact 1:***

- **Email:** Dalia.ghalwash@bue.edu.eg

- **Name:** Dalia Ghalwash, Phd

- **Phone:** 01005120159

- **Role:** CONTACT

***Contact 2:***

- **Email:** asmaa.aboubakr@bue.edu.eg

- **Name:** Asmaa A Ras, Phd

- **Phone:** 01098015060

- **Role:** CONTACT

**Country:** Egypt

**Facility:** The British University in Egypt

### IPD Sharing Statement Module

**Description:** Confidentiality of data: All data will be stored in an Excel sheet for research purposes and respecting patient confidentiality. Patients have the right to withdraw from the research at any point for any reason and with no penalty subject to them.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Bang LM, Buntting C, Molan P. The effect of dilution on the rate of hydrogen peroxide production in honey and its implications for wound healing. J Altern Complement Med. 2003 Apr;9(2):267-73. doi: 10.1089/10755530360623383.

**PMID:** 12804080

**Citation:** Eisen D, Carrozzo M, Bagan Sebastian JV, Thongprasom K. Number V Oral lichen planus: clinical features and management. Oral Dis. 2005 Nov;11(6):338-49. doi: 10.1111/j.1601-0825.2005.01142.x.

**PMID:** 16269024

**Citation:** Embil JA, Stephens RG, Manuel FR. Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can Med Assoc J. 1975 Oct 4;113(7):627-30.

**PMID:** 1181018

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009059

- Term: Mouth Diseases

- ID: D000009057

- Term: Stomatognathic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC07

- Name: Mouth and Tooth Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M17206

- Name: Ulcer

- Relevance: LOW

- As Found: Unknown

- ID: M16070

- Name: Stomatitis

- Relevance: HIGH

- As Found: Stomatitis

- ID: M16071

- Name: Stomatitis, Aphthous

- Relevance: HIGH

- As Found: Aphthous Stomatitis

- ID: M12019

- Name: Mouth Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12017

- Name: Stomatognathic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T455

- Name: Aphthous Stomatitis

- Relevance: HIGH

- As Found: Aphthous Stomatitis

### Condition Browse Module - Meshes

- ID: D000013280

- Term: Stomatitis

- ID: D000013281

- Term: Stomatitis, Aphthous

### Intervention Browse Module - Ancestors

- ID: D000000893

- Term: Anti-Inflammatory Agents

- ID: D000005938

- Term: Glucocorticoids

- ID: D000006728

- Term: Hormones

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: Ot

- Name: Other Dietary Supplements

- Abbrev: HB

- Name: Herbal and Botanical

### Intervention Browse Module - Browse Leaves

- ID: M16974

- Name: Triamcinolone

- Relevance: HIGH

- As Found: 10 hours

- ID: M16975

- Name: Triamcinolone Acetonide

- Relevance: HIGH

- As Found: 10 hours

- ID: M237966

- Name: Triamcinolone hexacetonide

- Relevance: HIGH

- As Found: 10 hours

- ID: M209573

- Name: Triamcinolone diacetate

- Relevance: HIGH

- As Found: 10 hours

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4854

- Name: Benzocaine

- Relevance: LOW

- As Found: Unknown

- ID: M9047

- Name: Glucocorticoids

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T433

- Name: Tannic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T315

- Name: Thyme

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000014222

- Term: Triamcinolone Acetonide

- ID: D000014221

- Term: Triamcinolone

- ID: C000005900

- Term: Triamcinolone hexacetonide

- ID: C000030262

- Term: Triamcinolone diacetate

### Misc Info Module

- Version Holder: 2024-05-31
