Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06381635
Status:
RECRUITING
Last Update Posted:
2024-04-24
First Post:
2024-04-20
Brief Title:
Effect of Aloe Vera Gel and Manuka Honey on Radiation Induced Oral Mucositis
Sponsor:
Ain Shams University
Organization:
Ain Shams University
Study Overview
Official Title:
Synergistic Effect of Aloe Vera Gel and Manuka Honey on Radiation Induced Oral Mucositis in Head and Neck Cancer Patients Randomized Controlled Clinical Trial
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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 18 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 89 It is described in five overlapping stages initiation upregulation message generation ulceration and healing 910
Radiation-induced oral mucositis shows hyperkeratosis of the oral mucosa after the dose of 10-20 Gy 68 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 1112 Effective management of oral mucositis is very important 1314
Honey is an important traditional medicine and prophylactic agent that has numerous beneficial health properties including its ability to facilitate healing1516 Honey helps in the reduction of ulceration and inflammation of the biological process of mucositis1718 Honey has been used to manage burns oral infections surgical wounds and pressure wounds1920 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 wv 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 ie 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 FGFs 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
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 89 It is described in five overlapping stages initiation upregulation message generation ulceration and healing 910
Radiation-induced oral mucositis shows hyperkeratosis of the oral mucosa after the dose of 10-20 Gy 68 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 1112 Effective management of oral mucositis is very important 1314
Honey is an important traditional medicine and prophylactic agent that has numerous beneficial health properties including its ability to facilitate healing1516 Honey helps in the reduction of ulceration and inflammation of the biological process of mucositis1718 Honey has been used to manage burns oral infections surgical wounds and pressure wounds1920 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 wv 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 ie 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 FGFs 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None