Evaluation of the Effect of Nigella Sativa for the Prophylaxis to Radiation Induced Dermatitis in Breast Cancer Patients

Study Overview
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Brief Summary
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Radiation induced dermatitis (RID) is one of the leading adverse events of radiation therapy, and if occurred could alter the course of therapy. The main pathways of RID is inflammation and oxidative stress on local and systemic bases. Nigella sativa is an herbal medicine whose anti-inflammatory and antioxidant activities have been proven in several clinical trials. Thus, the aim of the present study is to evaluate the efficacy of Nigella sativa as a prophylactic method against the development of RID.

Detailed Description
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Radiation induced dermatitis (RID) is one of the most commonly reported adverse events of breast radiation therapy (RT).Radiation therapy toxicity is exhibited within hours to weeks of exposure and persisting throughout the course of treatment. Radiation induced dermatitis is a result of generation of reactive oxygen species (ROSs), which in return induces epidermal and dermal inflammatory responses. Radiation causes structural tissue damage, which trigger production of pro-inflammatory mediators; as NF-κB, iNOS, COX-2, EGFR, MCP-1, and cytokines such as IL-1, IL-2, IL-6, TNF-a, and IFN- γ, and immune-stimulatory response; involving an increased movement of leukocytes from the blood into the irradiated tissues. Subsequently erythema, ulceration, and edema are developed. This is then followed by thinning of the epidermis, accompanied with degeneration of glands, which manifests as dry desquamation. If damage to the basal cells and glands is more severe, moist desquamation occur. From previous, it can be deduced that inflammatory response plays a significant role in the radiotherapy induced dermatitis. There are many agents that are used in the management of RID in the clinical settings, however, up till now there is none supported by the guidelines. Radiation induced dermatitis occurrence, not only could it impair the patient's quality of life but it could also affect the RT course of treatment, which could negatively influence the cancer treatment. Therefore more effort is needed to find a method of prevention of RID, resulting from breast RT, especially that there is no standard of care for prophylaxis to the radiation induced dermatitis (RID). Nigella sativa is herbal medicine that has been widely used in different parts of the world by different cultures. It has been used traditionally as a remedy for several diseases including fever, cough, chronic headache, dizziness, back pain, dysmenorrhea, obesity, diabetes, infection and inflammation, hypertension, and gastrointestinal disorders such as flatulence, and dysentery. Preclinical and clinical studies have demonstrated the anti-inflammatory, immunomodulatory, antioxidant, analgesic, and antimicrobial properties of N. sativa. Thymoquinone (TQ) is the prominent constituent of Nigella sativa, to which the biological properties have been attributed. Thymoquinone can act as a potent free radical and superoxide radical scavenger at both nanomolar and micromolar range, respectively. As well as, its beneficial effects on antioxidant enzymes, and its detrimental effects on pro-inflammatory mediators/cytokines, and pro-inflammatory transcription factor; nuclear factor kappa B (NF-κB). Based on literature, Nigella sativa has been shown to have antioxidant and anti-inflammatory effects. As, both the fixed oil of N. sativa, as well as thymoquinone (the main compound of the essential oil), were proven to inhibit non-enzymatic lipid peroxidation and have an appreciable free radical scavenging properties. Furthermore, orally administered Nigella sativa oil showed a reduction of IL-4 and NO production in rats. Additionally, Thymoquinone showed anti-inflammatory activity through inhibition of cyclooxygenase (COX) and 5-lipooxygenase (5-LPO), as well as through lowering TNF-α and IL-1β levels in arthritis in rats. It is worth mentioning that thymoquinone was proven to significantly reduce pancreatic ductal adenocarcinoma cell synthesis of MCP-1, TNF-a, IL-1β and Cox-2. It also inhibited the constitutive and TNF-a-mediated activation of NF-kB. Hence, many clinical trials have been using Nigella sativa, to see its anti-inflammatory and antioxidant effects in different indications including its anti-inflammatory effect in treatment of oral mucositis in head and neck cancers patients, and managing dermatitis in breast cancer patients, and its antioxidant effect in patients with psoriasis, and acute tonsillo-pharyngitis, and many more, where Nigella sativa showed to be not only safe but effective as well. Nigella sativa oil, Baraka ® gelatin capsules, has been used in doses up to 80 mg/kg/day in children with acute lymphoblastic leukemia, in the protection against doxorubicin-induced cardiac toxicity and in the protection against Methotrexate induced hepatotoxicity, where it was effective and safe.

Official Title
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Evaluation of the Effect of Nigella Sativa for the Prophylaxis to Radiation Induced Dermatitis in Breast Cancer Patients

Conditions
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Radiation Dermatitis

Intervention / Treatment
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* Drug: Imtenan Oil
* Drug: Baraka Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive, early stage breast carcinoma scheduled for adjuvant radiotherapy. Women aged ≥18 years. Exclusion Criteria: Prior exposure to radiotherapy Patients with generalized skin disorder Patients who failed to sign the written consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group I (control): Patients will not receive any prophylactic intervention, as there is no standard of care for prophylaxis to the radiation induced dermatitis (RID). Group II (Topical intervention): Patients will receive Imtenan ® N. sativa oil apply 1.5 mls; twice daily; not sooner than 2 hours before and after radiation therapy; from day 1 of radiation therapy till the end. Group III (Oral intervention): Patients will receive Baraka ® N. sativa gelatin capsules; 40mg/Kg/day; from day 1 of radiation therapy till the end
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group I (control)<br>Patients will not receive any prophylactic intervention, as there is no standard of care for prophylaxis to the radiation induced dermatitis (RID). | |
| Experimental: Group II (Topical intervention)<br>Patients will receive Imtenan ® N. sativa oil apply 1.5 mls; twice daily; not sooner than 2 hours before and after radiation therapy; from day 1 of radiation therapy till the end. | Drug: Imtenan Oil<br>* Cold Press Oil<br>|
| Experimental: Group III (Oral intervention)<br>Patients will receive Baraka ® N. sativa gelatin capsules; 40-80 mg/Kg/day; from day 1 of radiation therapy till the end | Drug: Baraka Capsules<br>* Soft Gelatin Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of development of radiation induced dermatitis | If the patient developed Radiation induced dermatitis or not | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Severity of RID developed | The severity of moist desquamation assessed by Common Terminology Criteria for Adverse Events (CTCAE, version6) criteria based on the clinical presentation. | 6 weeks | 
| Evaluation of Pain Intensity | Pain related assessment will be done through a Visual Analog Scale, with 0 being No pain and 10 being unbearable pain | 6 weeks | 
| Evaluation of Incidence of Treatment-Emergent Adverse Events | Patients will be educated and instructed to report any adverse events | 6 weeks | 
| Evaluation of Quality of life | Skin-related quality of life assessed through the Dermatology Life Quality Index (DLQI) | 6 weeks | 
| Evaluation of Time to develop grade 2 RID | Time to develop grade 2 RID incidence, will be assessed by Common Terminology Criteria for Adverse Events (CTCAE, version6) criteria based on the clinical presentation. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nigella sativa, Black seed, Baraka, Radiation induced dermatitis, Breast cancer