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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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House Dust Mite Allergy

Intervention / Treatment
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* Drug: Nigella Sativa Oil
* Drug: Allergen Specific Immunotherapy
* Drug: Standard pharmacotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Group<br>Control group will receive allergen specific immunotherapy and standard pharmacotherapy | Drug: Allergen Specific Immunotherapy<br>* 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.<br>Drug: Standard pharmacotherapy<br>* Standard pharmacotherapy as indicated based on patient's symptoms i.e none, antihistamine, corticosteroids, bronchodilators, etc.<br>|
| Experimental: Experimental Group<br>Experimental group will receive allergen specific immunotherapy, standard pharmacotherapy, and nigella sativa oil | Drug: Nigella Sativa Oil<br>* In this study, we use nigella sativa oil (NSO), which are packed in capsule. One capsule contained 550 mg of nigella sativa oil.<br>* Other names: Habbatussauda Oil MADINAH;Drug: Allergen Specific Immunotherapy<br>* 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.<br>Drug: Standard pharmacotherapy<br>* Standard pharmacotherapy as indicated based on patient's symptoms i.e none, antihistamine, corticosteroids, bronchodilators, etc.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 (deﬁnite 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) | 
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| TGF-β | Examination for TGF-β 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) | 
| 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) | 
| 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) | 
| IFN-γ | Examination for IFN-γ 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) | 
| 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) |