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

NCT ID: NCT05693597

Last Updated: 2024-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-24
• Study Completion Date: 2024-02-20

Brief Summary

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

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.

Conditions

Radiation Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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 Type: NO_INTERVENTION

No interventions assigned to this group

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 Type: EXPERIMENTAL

Imtenan Oil

Intervention Type: DRUG

Cold Press Oil

Group III (Oral intervention)

Patients will receive Baraka ® N. sativa gelatin capsules; 40-80 mg/Kg/day; from day 1 of radiation therapy till the end

Group Type: EXPERIMENTAL

Baraka Capsules

Intervention Type: DRUG

Soft Gelatin Capsules

Interventions

Imtenan Oil

Cold Press Oil

Intervention Type: DRUG

Baraka Capsules

Soft Gelatin Capsules

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: collaborator

German University in Cairo

OTHER

Sponsor Role: lead

Responsible Party

Mayar Waleed Salaheldin Aly

Clinical Pharmacy Lecturer Assistant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mayar Waleed Salaheldin Aly, M.Sc.

Role: PRINCIPAL_INVESTIGATOR

German University in Cairo

Locations

Ain Shams University Hospital

Cairo, , Egypt

Countries

Egypt

Related Links

https://www.dovepress.com/radiation-induced-skin-reactions-mechanism-and-treatment-peer-reviewed-fulltext-article-CMAR

Radiation-induced skin reactions: mechanism and treatment

https://link.springer.com/article/10.1007/s00520-013-1896-2

Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC Skin Toxicity Study Group

https://link.springer.com/article/10.1007/s00520-006-0063-4

The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline

http://www.bccancer.bc.ca/nursing-site/Documents/Symptom%20Management%20Guidelines/14RadiationDermatitis.pdf

Symptom Management Guidelines: RADIATION DERMATITIS

https://scialert.net/abstract/?doi=pjbs.2004.441.451

A Review of Medicinal Uses and Pharmacological Activities of Nigella sativa

https://pubmed.ncbi.nlm.nih.gov/10925395/

Antioxidant activity of Nigella sativa essential oil

https://pesquisa.bvsalud.org/portal/resource/pt/ibc-177883

Ameliorating effects of Nigella sativa oil on aggravation of inflammation, oxidative stress and cytotoxicity induced by smokeless tobacco extract in an allergic asthma model in Wistar rats

https://innovareacademics.in/journals/index.php/ijcpr/article/view/35704

Anti-Inflammatory Effect of Nigella Sativa Oil on Chemoradiation-Induced Oral Mucositis in Patients With Head and Neck Cancers

https://www.jceionline.org/article/evaluation-of-efficacy-safety-and-antioxidant-effect-of-nigella-sativa-in-patients-with-psoriasis-a-3557

Evaluation of efficacy, safety and antioxidant effect of Nigella sativa in patients with psoriasis: A randomized clinical trial

https://www.dustri.com/article_response_page.html?artId=4697&doi=10.5414/CPP46295&L=0

Symptomatic treatment of acute tonsillo-pharyngitis patients with a combination of Nigella sativa and Phyllanthus niruri extract

https://europepmc.org/article/med/31964219

Protective role of black seed oil in doxorubicin-induced cardiac toxicity in children with acute lymphoblastic leukemia

https://www.longdom.org/open-access/protective-effect-of-nigella-sativa-oil-against-methotrexate-induced-hepatotoxicity-in-children-with-acute-lymphoblastic-leukemia-2329-6917.1000123.pdf

Protective Effect of Nigella sativa Oil against Methotrexate Induced Hepatotoxicity in Children with Acute Lymphoblastic Leukemia

https://tahomaclinic.com/Private/Articles3/RA/Gheita%202012%20-%20Effectiveness%20of%20Nigella%20sativa%20oil%20in%20rheumatoid%20arthritis.pdf

Effectiveness of Nigella sativa Oil in the Management of Rheumatoid Arthritis Patients: A Placebo Controlled Study

https://pubmed.ncbi.nlm.nih.gov/14669258/

Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases

https://europepmc.org/article/med/8033378

Dermatology Life Quality Index (DLQI)-a simple practical measure for routine clinical use

Other Identifiers

N.sativavsRID BreastCancerpt.

Identifier Type: -

Identifier Source: org_study_id