Trial Title:
Effect of Aloe Vera Gel and Manuka Honey on Radiation Induced Oral Mucositis
NCT ID:
NCT06381635
Condition:
Radiation Mucositis
Conditions: Official terms:
Mucositis
Stomatitis
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Double (Participant, Outcomes Assessor)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Manuka honey mixed with aloe vera gel
Description:
a mix gel of manuka honey and with aloe vera honey (1:1) mixed in water bath to get a
homogenous mix is then packed in unmarked bottles.
Arm group label:
Control group
Arm group label:
intervention group
Summary:
The goal of this [ type of study: Clinical trial] is to test effectiveness of Aloe Vera
Gel and Manuka Honey in management of Radiation Induced Mucositis in head and neck cancer
patients.
The main question [s] ] is to [ learn about, test, compare etc.] it aims to answer are:
1. Is Aloe Vera Gel and Manuka Honey effective in management of Radiation Induced
Mucositis?
2. Does Aloe Vera Gel and Manuka Honey affect the level of TGFβ1 and EGF in saliva of
patients with radiation induced mucositis? participants will be asked to apply Aloe
Vera Gel and Manuka Honey or saline three times daily during radiotherapy and 6
months after radiotherapy.
Detailed description:
Head and neck cancer is the eighth common type among all cancer types all over the world
[1] The treatment comprises surgery, radiotherapy, chemotherapy or a combination escorted
by restoration therapy, and social support [2] Radiotherapy leads to irreversible loss of
the reproductive integrity, the cell cycle necessary for cell growth, apoptosis, and
necrosis of cancer cells [3] Conventional fraction size ranges from 1.8 to 3 Grays (Gy)
per fraction over 4-6 weeks [4] The accumulative dose of radiation for the primary
treatment of head and neck cancer treatment is 60-70 Gy, depending on the irradiation of
the tumor [5].
Radiation affects malignant cells and is also absorbed by the oral mucosa and
gastrointestinal mucosa, especially in rapidly dividing cells [6] Oral mucositis is the
most frequent, distressing, painful, clinical side effect of radiotherapy [7] It is
defined as an inflammatory lesion of oral mucosa resulting from the cancer therapy
typically manifesting as atrophy, swelling, erythema, ulceration, and pseudomembrane
formation [8,9] It is described in five overlapping stages: initiation, upregulation,
message generation, ulceration, and healing [9,10].
Radiation-induced oral mucositis shows hyperkeratosis of the oral mucosa after the dose
of 10-20 Gy [6,8] Erythema is the first clinical sign seen on the oral mucosa, and
severity of mucositis reaches at a dose of 30 Gy. After the completion of radiotherapy,
the symptoms abate in 2-6 weeks [11,12] Effective management of oral mucositis is very
important [13,14].
Honey is an important traditional medicine and prophylactic agent that has numerous
beneficial health properties including its ability to facilitate healing.[15,16] Honey
helps in the reduction of ulceration and inflammation of the biological process of
mucositis.[17,18] Honey has been used to manage burns, oral infections, surgical wounds,
and pressure wounds.[19,20]. Honey was applied to the oral mucosa of patients undergoing
radiotherapy which is beneficial in limiting the severity of oral mucositis. Honey is a
natural product with rich nutritional properties that is economical and a pleasant agent
for managing mucositis [21].
Manuka honey is a monofloral honey, produced from the nectar of flowers of Manuka tree.
This variety is produced from the Apis mellifera honey bees, using New Zealand Manuka
plants producing specific floral-variety named as Leptospermum scoparium [22]. Manuka
honey is usually rated using a classification system known as the Unique Manuka Factor
(UMF), which reflects the equivalent concentration of phenol (%, w/v) required to produce
the same antibacterial activity as honey.
The composition of Manuka honey consists of carbohydrates, minerals, proteins, fatty
acids, phenolic and flavonoid compounds. Although such compounds are found in other types
of honey, other unique features also occur in Manuka honey, such as an unusually high
level of methylglyoxal (MGO) formed from dihydroxyacetone (DHA) which correlates with
antibacterial activity [23, 24]. Kato et al. also noted the occurrence of methyl
syringate glycoside (leptosperin) as a unique maker for Manuka honey authentication [25].
Interestingly, the UMF rating of Manuka honey strongly correlates with MGO equivalence
and antibacterial activity but the relation is not wholly understood [26]. In addition to
antibacterial activity [22, 26], UMF honey has the ability to stimulate macrophages
through Apalbumin 1 protein to release mediators such as TNF-α, IL-1β and IL-6, which are
needed for reducing microbial infections and helping in tissue healing [27]. Manuka honey
shows antioxidant and anticancer properties, which are considered due to its
constituents-phytochemicals working as active bio-compounds [28, 29].
Aloe Vera (AV) is a cactus-like plant that grows readily in hot, dry climates. It belongs
to the Liliacea family, of which there are about 360 species. Only two species are grown
commercially: Aloe barbadensis Miller and Aloe aborescens. The parenchymatous cells in
the fresh leaves of aloe vera secrete colorless mucilaginous gel (i.e., Aloe vera gel)
that contains 98-99% water and 1-2% active compounds [30, 31] Aloe vera gel has various
pharmacological actions like antibacterial, antifungal, anti-inflammatory, antioxidant,
antitumour, hypoglycaemic properties and immune boosting. Therefore it is used
traditionally as nutritional drinks, moisturizer, healing agent in cosmetics, diabetic
patients, sun burn, wounds and digestive tract disorders, there is no adverse effect
[32].
Aloe vera gel had also been used in dentistry and showed good results. It had been used
for treatment of over extraction socket and endodontic medicament. Various dentifrices
also contains Aloe vera gel as its constituent because of its medicinal property [33-34].
Studies have demonstrated that aloe vera has an important therapeutic uses in the
management of oral lesions such as oral lichen planus, oral submucous fibrosis, radiation
induced mucositis, burning mouth syndrome, xerostomia, recurrent apthous ulcers [31].
Transforming growth factor-β (TGF-β) is a family of related proteins that regulate many
cellular processes including growth, differentiation, extracellular matrix formation and
immunosuppression [35]. TGF-β protein is produced by nearly all normal cells and
functions through a complex cell surface receptor system [36].
The three mammalian isoforms of TGF-β (TGF-βs 1, 2, and 3) have similar but distinct
functions and are approximately 70% identical in amino acid sequence. Transforming growth
factor-β (TGF-β) proteins and their antagonists have entered clinical trials. These
multi-functional regulators of cell growth and differentiation induce extracellular
matrix proteins and suppress the immune system making TGF-βs useful in treatment of
wounds with impaired healing, mucositis, fractures, ischemia-reperfusion injuries, and
autoimmune disease. In diseases such as keloids, glomerulonephritis and pulmonary
fibrosis, excessive expression of TGF-β has been implicated as being responsible for
accumulation of detrimental scar tissue. In these conditions, agents that block TGF-β
have prevented or reversed disease. Similarly, in carcinogenesis, blocking TGF-β activity
may be valuable in stimulating an immune response towards metastasis. As these blocking
agents receive approval, we will likely have new therapies for previously recalcitrant
diseases [37]. It has been stated that transforming growth factor-β3 (TGF-β3) negatively
regulates epithelial cell proliferation and reduces the incidence of oral mucositis [38].
A great number of growth factors and cytokines are involved in the wound site [39]. Of
the growth factors, basic fibroblast growth factor (bFGF), transforming growth factor
(TGF-b), and platelet-derived growth factor (PDGF) are anti-inflammatory and the most
important in the wound healing process [40]. The bFGF (FGF-2) is a member of the FGF's
family and has been shown in several studies to be an essential growth factor for
fibroblast and vascular endothelial cell [41]. bFGF is increased in acute wound healing
and plays a role in granulation tissue formation, re-epithelization, and tissue
remodeling [42]. Although clinical studies have shown that bFGF was not successful in the
treatment of diabetic foot ulcers, topical bFGF application has been found to increase
the healing of burns and venous ulcers [43, 44, 45]. Moreover, TGF-β and PDGF are both
crucial for inflammation, granulation, angiogenesis, connective tissue regeneration,
re-epithelization, and remodeling which stimulate macrophages by increasing the secretion
of other growth factors [43, 46]. They stimulate collagen production, affect matrix
formation, and inhibit metalloproteinase (MMP) activity, which degrades collagen
deposition. Levels of PDGF, TGF-β, and FGF are decreased in chronic wounds.
Epidermal growth factor (EGF), first discovered in the submaxillary gland of a rat in
1962, comprises a single-chain polypeptide containing 53 amino acids [47, 48]. EGF was
later discovered in various normal tissues and body fluids, including the skin, mucosa,
tears, cornea, saliva, milk, semen, and fluids secreted by the duodenal glands [49, 50].
EGF helps maintain tissue homeostasis by regulating epithelial cell proliferation,
growth, and migration. It also induces angiogenesis, which provides nutritional support
for tissues. Thus, EGF plays an important role in wound healing and tissue generation and
may be useful in the treatment of radiation-induced oral mucositis [51, 52].
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- a) Patients with a confirmed histologic diagnosis of H&N malignancy who are referred
to non-palliative radiotherapy in the oral cavity.
b) Patient who is receiving radiation therapy with IMRT or 3D techniques. c)
Patients received 50-70 Gy of total radiation at the rate of 2 Gy/fraction daily and
5 fractions/week.
d) Patient who received concurrent chemotherapy with radiotherapy e) Presence of
Oral Mucositis f) Age 20-70 years old g) Willing to participate in the study. h)
Able to complete the study assessments.
Exclusion Criteria:
- a) Have a confirmed or medically treated diabetes mellitus b) Radiotherapy within
the last 6 months prior to this study c) Vulnerable patients
Gender:
All
Minimum age:
20 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
ain shams University
Address:
City:
Cairo
Zip:
11565
Country:
Egypt
Status:
Recruiting
Contact:
Last name:
hani wlliam, MD
Phone:
+20 0001000093885
Email:
ethicscommittee.fdasurec@gmail.com
Facility:
Name:
Fatma E.Sayed
Address:
City:
Cairo
Country:
Egypt
Status:
Recruiting
Contact:
Last name:
Fatma E. Hassanein, PHD
Phone:
+201000093885
Email:
fatmahassanein@dent.asu.edu.eg
Contact backup:
Last name:
Asma Abou Bakr
Email:
Asmaa.Aboubakr@bue.edu.eg
Start date:
April 1, 2024
Completion date:
January 1, 2025
Lead sponsor:
Agency:
Ain Shams University
Agency class:
Other
Source:
Ain Shams University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06381635
