Download RDBPCT for Black Seed Supplementation in Asthma

RDBPCT for Black Seed
Supplementation in Asthma:
Methodology Development
Abdulrahman Koshak
PharmD, MSc, PhD candidate
UCL School of Pharmacy, London
Faculty of Pharmacy, King Abdulaziz University, Jeddah
‫الحديث‬
‫عن أيب هريرة رضي هللا عنه أنه مسع رسول هللا صلى هللا عليه وسلم يقول‬
‫( في الحبة السوداء شف اء من كل داء إال السام )‬
‫متفق عليه‬
Black Seed (Nigella sativa)
• Distinguished historical and
religious focus
• Arabic, Unani, Ayurvedic, and
Chinese medicine
– In bible: the curative black cumin
– In Isaiah, mentioned in Hebrew word
“Ketsah”
– In Islam, mentioned by prophet as a
cure for all diseases except death
Chemical Composition
Fixed oils
40%
Alkaloids
Volatile oils
1.6%
BS
Saponins
Other
Active Compound
Thymoquinone
Randomised Double-Blind PlaceboControlled Clinical Trial
(RDBPCT)
Method development
1st Step: Literature Review
• Searching medical databases such as (PubMed,
EMBASE, google scholar) for an evidence of
black seed benefits in bronchial asthma
• 15 pre-clinical studies found a positive effect of
Black seed or TQ in different cellular and animal
models of asthma.
• 4 preliminary clinical trials reported its possible
effectiveness in asthma (water extract, powdered,
oil)
2nd Step: Research Team
Formation
• Specialist medical doctor/s
• Medical statistician
• Pharmaceutical (pharmacognosy)
3rd step: Trial design
3.1. Resources Guide for Study
Protocol
• Guidelines:
– European Medicines Agency's scientific guidelines 2013 on clinical
investigation of medicinal products for treatment of asthma
• Journal articles:
– Adcock IM, Caramori G, Chung KF. New targets for drug development in
asthma. Lancet 2008;372:1073–87. doi:10.1016/S0140-6736(08)61449-X
– Szefler SJ, Wenzel S, Brown R, et al. Asthma outcomes: biomarkers. J Allergy
Clin Immunol 2012;129:S9–23. doi:10.1016/j.jaci.2011.12.979
• Textbooks:
– Hansel TT, Barnes PJ (eds): New Drugs and Targets for Asthma and COPD.
Prog Respir Res. Basel, Karger 2010, vol 39, pp 3–23
• Research team recommendations
3.2 Sample Size
• Sample size is estimated based on the
primary endpoint (Asthma Control
Test “ACT”)
• nQuery Advisor software
Research Type
• Prospective, double-blind, placebocontrolled, randomised clinical intervention
study of Nigella sativa oil supplementation
DBPC-RCT
• Phase II clinical trial
Inclusion Criteria
• Adult male/female (age 18-65 years)
• Partially controlled and Uncontrolled
asthmatic patient based on GINA guidelines
(ACT score 5-20)
• No severe asthma exacerbation in the last 4
weeks
• Able to obtain consent
Exclusion Criteria
• Co-morbid serious conditions such as; cancer,
renal, hepatic, cardio-vascular, gastrointestinal
diseases, mental health conditions and respiratory
disorder such as TB and COPD.
• Smoking history
• Pregnant women
• Known history of hypersensitivity to Black seed.
• Taking Black seed or medications that interact
with it: Anticoagulant/Antiplatelet, Antidiabetic,
Antihypertensive, CNS depressants, and
Immunosuppressant drugs.
Step 4: Ethical approval &
registration
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•
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•
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UCL ethics (6419/002)
KAU ethical committee (95-15)
Saudi FDA
Ministry of Health
www.clinicaltrials.gov (NCT02407262)
Title: Potential Benefits of Nigella sativa Oil Supplementation
on Asthma Inflammation and Outcome
SFDA Requirements
Step 5: Arrangements for Study
Locations
• Medical outpatient clinics at KAUH
• Private allergy clinic at KAUH and Sameer Abbas
medical centre
• Primary care centres at MOH
Step 6: determination and
preparation of the study product
Which Black seed?
Quality Study of Black Seed
(Metabolomic method)
Variability of Black Seed (Nigella sativa L.) samples
from Different Origins: Using NMR analytical tool
Score plot of 23 black seed samples
Score Plot of 6 Oil Products
Thyomoquinone Analysis (HPLC)
TQ Conc. (W/W) %
3
2.5
2
1.5
1
0.5
0
Sample Sample Sample Sample Sample Sample Sample Sample
1
2
3
4
5
7
9
10
Anti-inflammatory
(in-vitro)
Analysis
Effect of Black seed extracts on
T-cells inflammatory mediators
Effect of Black seed extracts on
T-cells inflammatory mediators
Effect of Black seed extracts on
A549 cells’ inflammatory mediator
Effect of Black seed extracts on
A549 cells’ inflammatory mediator
Effect of Black seed extracts on
signalling pathways in A549 cells
Study Product and Placebo
• Marnys® Cuminmar (Nigella sativa oil, 500mg)
SFDA licensed.
• Placebo (olive oil)
• Dose: one capsules (500 mg) twice daily (total 1
g/day) for 4 weeks.
Step 7: Randomisation and Blinding
• An external medical scientist created block
randomisation table using the website
(https://www.sealedenvelope.com) with block
sizes of 2,4 for 100 sample size.
• A list of unique codes has been
generated for each box of trial
medications (both treatment and
placebo)
Step 8: Outcomes measurement
arrangements
• Asthma Control Test • lung function (PFT)
(ACT)
Step 8: Outcomes measurement
arrangements
• Complete blood count (CBC)
• Serum biomarkers (Total Immunoglobulins,
Inflammatory mediators such as: Cytokines,
chemokines, cell singling proteins)
Conclusions
• In order to design the methodology of a RDBPCT
of black seed in asthma, at least eight
developmental steps were implemented.
• This work may provide a guidance for steps to
conduct a RDBPCT on herbal medicines in the
context of saudi healthcare system.
Acknowledgment
Prof Emad Koshak
Prof Siraj Wali
Prof Omar AlAmoudi
Dr Abdulrahman
Demerdash
Dr Majdi Qotob
Dr Peter Pushparaj
Dr Li Wei
Prof Michael
Heinrich
• Immunology lab at KAUH and KFMRC
• Medical residents, nurses, and staff
References
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Ahmad, A. et al., (2013). A review on therapeutic potential of Nigella sativa: A miracle herb.
Asian Pacific Journal of Tropical Biomedicine, 3(5), pp.337–352. Available at:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3642442&tool=pmcentrez&rende
rtype=abstract [Accessed March 20, 2013].
Ali, M.A. et al., (2012). CHARACTERISTICS OF OILS AND NUTRIENT CONTENTS OF
NIGELLA SATIVA LINN. AND TRIGONELLA FOENUM-GRAECUM SEEDS. Chenmical
Society of Ethiopia, 26(1), pp.55–64.
Booker, A. et al., (2011). Metabolomic profiling of saw palmetto products using proton-NMR
spectroscopy and multi-variate analysis. Planta Medica, 77(12), p.1249. Available at:
https://www.thieme-connect.de/DOI/DOI?10.1055/s-0031-1282148 [Accessed July 30,
2013].
Botnick, I. et al., (2012). Distribution of primary and specialized metabolites in Nigella sativa
seeds, a spice with vast traditional and historical uses. Molecules, 17(9), pp.10159–77.
Available at: http://www.ncbi.nlm.nih.gov/pubmed/22922285 [Accessed March 16, 2013].
Datta, A.K. et al., (2012). BLACK CUMIN (NIGELLA SATIVA L.) – A REVIEW. Journal of
Plant Development Sciences, 4(1), pp.1–43.
Fidele, T., Piater, L. & Dubery, I., (2013). Plant metabolomics: A new frontier in
phytochemical analysis. South African Journal of Science, 109(5/6), p.11. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/23107118 [Accessed March 6, 2013].
* NaturalMedicines, 2014. Black Seed Monograph. Available at:
Refrences
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Khare, C.P., (2004). Encyclopedia of Indian Medicinal Plants: Rational Western
Therapy, Ayurvedic and Other Traditional Usage, Botany, Springer Verlag. Available at:
http://books.google.co.uk/books?id=mz_RAAAACAAJ.
Kim, H.K., Choi, Y.H. & Verpoorte, R., (2010). NMR-based metabolomic analysis of
plants. Nature protocols, 5(3), pp.536–49. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/20203669 [Accessed May 27, 2013].
Liu, X., Abd El-aty, A.M. & Shim, J., (2011). Various Extraction and Analytical
Techniques for Isolation and Identification of Secondary Metabolites from Nigella sativa
Seeds. Mini-Reviews in Medicinal Chemistry, 11, pp.947–955.
Michel, C.G. et al., (2011). Phytochemical and biological investigation of the extracts of
Nigella sativa L. seed waste. Drug testing and analysis, 3(4), pp.245–54. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/21309000 [Accessed May 15, 2013].
Nickavar, B. et al., (2003). Chemical composition of the fixed and volatile oils of Nigella
sativa L. from Iran. Zeitschrift für Naturforschung, 58(9-10), pp.629–31. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/14577620.
Okazaki, Y. & Saito, K., (2012). Recent advances of metabolomics in plant
biotechnology. Plant biotechnology reports, 6(1), pp.1–15. Available at:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3262138&tool=pmcentrez&re
ndertype=abstract [Accessed April 8, 2013].
Trevor, J.L. & Deshane, J.S., 2014. Refractory asthma: mechanisms, targets, and
‫وهو في الصحيحين وغيرهما‪ ،‬ولفظه عند البخاري عن خالد بن‬
‫سعد قال‪ :‬عليكم بهذه الحبيبة السوداء‪ ،‬فخذوا منها خمسا ً أو سبعا ً‬
‫فاسحقوها ثم اقطروها في أنفه بقطرات زيت في هذا الجانب وفي هذا‬
‫الجانب‪ ،‬فإن عائشة حدثتني أنها سمعت رسول هللا صلى هللا عليه وسلم‬
‫يقول‪ :‬إن هذه الحبة السوداء شفاء من كل داء إال من السام‪ ،‬قلت‪ :‬وما السام‪،‬‬
‫قال‪ :‬الموت‪.‬‬