The Efficacy of Nigella Sativa in Children With House Dust Mite-Induced Respiratory Allergy Receiving Immunotherapy

House Dust Mite Allergy Clinical Trial

Official title:

The Efficacy of Nigella Sativa in Children With House Dust Mite-Induced Respiratory Allergy Receiving Immunotherapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05450289
• Other study ID #: CRP/2022/VI/001
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2022
• Est. completion date: May 2023

Study information

• Verified date: July 2022
• Source: Universitas Airlangga
• Contact: Ida Bagus Ramajaya Sutawan, MD
• Phone: +62811392440
• Email: ramasutawan[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An experimental study aims to investigate the efficacy of Nigella Sativa in children with house dust mite (HDM)-induced respiratory allergy receiving immunotherapy. This study observes symptom, medication, combine symptom-medication score, quality of life (QoL), skin prick test, IL-4, TGF-β, IL-10, IgG4 specific HDM, IgE Specific HDM, and IFN-γ as the outcome. This study will be done on 40 subjects (20 subjects in control group and 20 subjects in experimental group), in children diagnosed with house dust mite-induced respiratory allergy such as allergic rhinoconjunctivitis and/or asthma, with an age of 2 to 17 years old, receiving allergen specific immunotherapy, not having an autoimmune disease, malignancy, nor chronic respiratory infection at the beginning of study, and has an approval from their parents. In control group, subjects will receive allergen specific immunotherapy and standard pharmacotherapy for underlying diagnose. In experimental group, subjects will receive nigella sativa oil for 14 weeks, allergen specific immunotherapy, and standard pharmacotherapy for underlying diagnose. All subjects will observe for 14 weeks during build up phase of immunotherapy. They will be monitored regularly, since this study starts, at each week, and at the end of this study. The symptom, medication, and combine symptom-medication score will be calculated at every session of monitoring. Quality of life (QoL), skin prick test, IL-4, TGF-β, IL-10, IgG4 specific HDM, IgE Specific HDM, and IFN-γ will be collected at the beginning and the end of this study.

Description:

House dust mite (HDM) is one of allergen that often cause respiratory allergy. In chronic condition respiratory allergy can have an impact in growth and development as well as the quality of life of a child. Children that strongly sensitized to house dust mite have the high risk of asthma and allergic rhinitis. Study in urban areas in Indonesia found that the prevalence of sensitization to HDM is quite high in elementary school children, which is 28.6%. House dust mites have even become an allergen with the most sensitization in junior and senior high school children in urban areas in Indonesia with a prevalence of 62.5%. Avoidance of allergens is actually the key to successful treatment of allergic diseases, but so far there is no proven effective HDM avoidance method to completely eliminate the HDM exposure. House dust mites-specific allergen immunotherapy is a solution for causal therapy in HDM allergies, because HDM-specific allergen immunotherapy will stimulate the immune system to become tolerant to HDM. Although immunotherapy has been shown to be effective in inducing tolerance in children with house dust mite-induced respiratory allergy, this process takes time where its effects are generally seen when entering the maintenance phase. One strategy that has recently been developed to increase therapeutic efficacy in medical therapy, including in allergic diseases is Complementary and Alternative Medicine (CAM) which includes the use of natural ingredients (vitamins, herbs, supplements), acupuncture, physiotherapy and others. Nigella sativa also known as black cumin is one of the herbs that are widely studied as a complementary and alternative therapy to increase the efficacy of standard therapy for allergic diseases. Nigella sativa contain several active components that have antihistamine effect, antioxidant, anti-inflammatory, and immunomodulatory effects in both in vitro and in vivo models. The main active component of nigella sativa that provides an immunomodulatory effect is thymoquinone (TQ). Nigella sativa extract can affect the process of allergic disease in various mechanisms. The immunomodulating effects of nigella sativa will increase the number of regulatory T cells (Treg) in allergic children. Treg will produce interleukin (IL)-10 which will suppress the activation of T helper (Th)2 cells, in addition IL-10 and Transforming Growth Factor-β (TGF-β) will stimulate B cells to produce more Immunoglobulin (Ig)G4 Specific. Nigella sativa also has an antihistamine effect by increasing mast cell stabilization, than it will prevent mast cell degranulation. It also has the effect of non-selectively inhibiting histamine receptors. As an anti-inflammatory and immunomodulatory effect, nigella sativa inhibits the enzymes cyclooxygenase (COX) and lipoxygenase (LO) thereby inhibiting the formation of prostaglandins and leukotrienes which are important inflammatory mediators in the allergic process. Based on the data above, the addition of nigella sativa will be able to help accelerate and increase the efficacy of immunotherapy in children with house dust mite-induced respiratory allergy. However, scientifically consistent evidence is still needed, while until now clinical trial study on these is still limited.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: May 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• Diagnosed with house dust mite-induced respiratory allergy such as allergic rhinoconjunctivitis, and/or asthma,
• Receiving allergen specific immunotherapy
• Parents want to follow the study by signing the informed consent

Exclusion Criteria:

• Autoimmune disease
• Malignancy
• Chronic respiratory infection
• Anatomical abnormalities of respiratory tract

Related Conditions & MeSH terms

• House Dust Mite Allergy
• Hypersensitivity

Intervention

Drug:
• Nigella Sativa Oil
In this study, we use nigella sativa oil (NSO), which are packed in capsule. One capsule contained 550 mg of nigella sativa oil.
• Allergen Specific Immunotherapy
In this study, we use the house dust mite allergen immunotherapy (Teaching Industry Allergen by Dr. Soetomo Hospital-Airlangga University, Surabaya, Indonesia) used was an extract of Dermatophagoides pteronyssinus via subcutaneous injection.
• Standard pharmacotherapy
Standard pharmacotherapy as indicated based on patient's symptoms i.e none, antihistamine, corticosteroids, bronchodilators, etc.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Universitas Airlangga

References & Publications (14)

4. Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, et al. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases. Allergologie. 2015;38(9):431-70.

Abbas AK, Lichtman andrew H, Pillai S. Basic Immunology : Fungtion and Disorders of the Immune System,. 2007.

Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013 May;3(5):337-52. doi: 10.1016/S2221-1691(13)60075-1. Review. — View Citation

Barlianto W, Wulandari D, Chusniyah M, Chandra Kusuma HMS, Prawiro SR. Improvement of th17/treg balance and asthma control test score by nigella sativa supplementation in asthmatic children: A new approach to managing asthma. Turkish J Immunol. 2018;6(1):1-7.

Caballero R, Grau A, Javaloyes G, Del Pozo S, León MÁ, Romero M, Casanovas M. Combination of Allergic Asthma Symptom and Medication Scores in Allergen Immunotherapy Trials: A Proposal. Int Arch Allergy Immunol. 2021;182(7):571-573. doi: 10.1159/000513543. Epub 2021 Jan 26. — View Citation

Calderón MA, Kleine-Tebbe J, Linneberg A, De Blay F, Hernandez Fernandez de Rojas D, Virchow JC, Demoly P. House Dust Mite Respiratory Allergy: An Overview of Current Therapeutic Strategies. J Allergy Clin Immunol Pract. 2015 Nov-Dec;3(6):843-55. doi: 10.1016/j.jaip.2015.06.019. Epub 2015 Sep 3. Review. — View Citation

Canonica GW, Baena-Cagnani CE, Bousquet J, Bousquet PJ, Lockey RF, Malling HJ, Passalacqua G, Potter P, Valovirta E. Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce. Allergy. 2007 Mar;62(3):317-24. Review. — View Citation

Gabet S, Rancière F, Just J, de Blic J, Lezmi G, Amat F, Seta N, Momas I. Asthma and allergic rhinitis risk depends on house dust mite specific IgE levels in PARIS birth cohort children. World Allergy Organ J. 2019 Oct 4;12(9):100057. doi: 10.1016/j.waojou.2019.100057. eCollection 2019 Sep. — View Citation

Kabir Y, Akasaka-Hashimoto Y, Kubota K, Komai M. Volatile compounds of black cumin (Nigella sativa L.) seeds cultivated in Bangladesh and India. Heliyon. 2020 Oct 27;6(10):e05343. doi: 10.1016/j.heliyon.2020.e05343. eCollection 2020 Oct. — View Citation

Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A, Lichius JJ, Kiesewetter H. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res. 2003 Dec;17(10):1209-14. — View Citation

Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, Durham SR, Jacobsen L, Malling HJ, Mösges R, Papadopoulos NG, Rak S, Rodriguez del Rio P, Valovirta E, Wahn U, Calderon MA; European Academy of Allergy and Clinical Immunology. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy. 2014 Jul;69(7):854-67. doi: 10.1111/all.12383. Epub 2014 Apr 25. — View Citation

Qiu J, Grine K. Complementary and Alternative Treatment for Allergic Conditions. Prim Care. 2016 Sep;43(3):519-26. doi: 10.1016/j.pop.2016.04.012. Review. — View Citation

Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005 Dec;5(13-14):1749-70. Epub 2005 Jul 1. Review. — View Citation

Soegiarto G, Abdullah MS, Damayanti LA, Suseno A, Effendi C. The prevalence of allergic diseases in school children of metropolitan city in Indonesia shows a similar pattern to that of developed countries. Asia Pac Allergy. 2019 Apr 20;9(2):e17. doi: 10.5415/apallergy.2019.9.e17. eCollection 2019 Apr. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change of Symptom score	The change from baseline Symptom Score at 14 weeks. The symptom score (SS) is divided in three domain symptoms which are nasal symptoms (Itchy nose, sneezing, runny nose, and blocked nose), conjunctival symptoms (itchy/red eyes and watery eyes), and lung symptoms (cough, wheeze, shortness of breath, and chest tightness). Each of the symptoms is scored from 0 to 3, considering the severity of each value. The final SS would be the sum of all individual symptom scores divided by the number of symptoms, being the range of SS from 0 to 3. The score is: 0 = no symptoms (or signs); 1 = mild symptoms (sign/ symptom clearly present, but minimal awareness; easily tolerated); 2 = moderate symptoms (de?nite awareness of sign/symptom that is bothersome but tolerable); 3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping).	At the beginning of the study (1st week) and at the end of the study (14th week)
Primary	The change of Medication score	The change from baseline Medication Score at 14 weeks. The medication score (MS) is divided in two domain with range of value from 0 to 3, first for allergic rhinoconjunctivitis medication, 0 = no use of medication, 1=use of oral and/or topical H1A, 2=use of intranasal corticosteroids with/without H1A; 3=use of oral corticosteroid with/without intranasal corticosteroids, with/without H1A. Second for lung/asthma medication, the score is 0=no use of medication, 0.5= SABA, 1=low-dose ICS, alternative: LTRA, 1.5=low dose ICS + LABA or medium dose ICS, 2=medium dose ICS+LABA, 2.5=high dose ICS+LABA, 3=high dose ICS+LABA+systemic corticosteroid	At the beginning of the study (1st week) and at the end of the study (14th week)
Primary	The change of Combination symptom-medication score	The change from baseline Combination Symptom-Medication Score at 14 weeks. The Combination symptom-medication score (CSMS) is the sum of SS (range 0-3) and MS (range 0-3). Therefore, the values of CSMS are in the range of 0-6.	At the beginning of the study (1st week) and at the end of the study (14th week)
Secondary	Pediatric Quality of Life Inventory (PedsQL)	The measured Quality of Life (QoL) outcomes using Pediatric Quality of Life Inventory (PedsQL). The items of PedsQL are grouped together on the actual questionnaire into four Scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning). Items are reversed scored and linearly transformed to a 0-100 scale. To reverse score, transform the 0-4 scale items to 0-100 as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better HRQOL (Health-Related Quality of Life)	At the beginning of the study (1st week), at the middle of study (8th week), and at the end of the study (14th week)
Secondary	Skin prick test	Skin prick test will be done using the house dust mite allergen (Teaching Industry Allergen by Dr.Soetomo Hospital-Airlangga University, Surabaya, Indonesia) used was an extract of Dermatophagoides pteronyssinus.	At the beginning of the study(1st week) and at the end of the study (14th week)
Secondary	IL-4	Examination for IL-4 using an enzyme-linked immunosorbent assay/ELISA, will be done by taking 3-5 ml of blood sample at the beginning and the end of the study	At the beginning of the study(1st week) and at the end of the study (14th week)
Secondary	TGF-ß	Examination for TGF-ß using an enzyme-linked immunosorbent assay/ELISA, will be done by taking 3-5 ml of blood sample at the beginning and the end of the study	At the beginning of the study(1st week) and at the end of the study (14th week)
Secondary	IL-10	Examination for IL-10 using an enzyme-linked immunosorbent assay/ELISA, will be done by taking 3-5 ml of blood sample at the beginning and the end of the study	At the beginning of the study(1st week) and at the end of the study (14th week)
Secondary	IgG4 specific HDM	Examination for IgG4 specific HDM using an enzyme-linked immunosorbent assay/ELISA, will be done by taking 3-5 ml of blood sample at the beginning and the end of the study	At the beginning of the study(1st week) and at the end of the study (14th week)
Secondary	IFN-?	Examination for IFN-? using an enzyme-linked immunosorbent assay/ELISA, will be done by taking 3-5 ml of blood sample at the beginning and the end of the study	At the beginning of the study(1st week) and at the end of the study (14th week)
Secondary	IgE Specific HDM	Examination for IgE specific HDM using an enzyme-linked immunosorbent assay/ELISA, will be done by taking 3-5 ml of blood sample at the beginning and the end of the study.	At the beginning of the study(1st week) and at the end of the study (14th week)