Randomized, placebo controlled, double blinded pilot superiority phase 2 trial to evaluate the effect of curcumin in moderate to severe asthmatics

Michele Quan, Abdullah Alismail, Noha Daher, Derrick Cleland, Sonia Chavan, Laren D Tan, Michele Quan, Abdullah Alismail, Noha Daher, Derrick Cleland, Sonia Chavan, Laren D Tan

Abstract

Background: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment.

Methods: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time.

Discussion: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19.

Trial registration: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://ichgcp.net/clinical-trials-registry/NCT04353310 .

Keywords: Anti-inflammatory; Anti-oxidant; Asthma; Curcumin; Moderate asthma; Severe asthma.

Conflict of interest statement

All authors declare they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Diagram that illustrates the mechanism of action of curcumin and the biologic effect

References

    1. Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann N Y Acad Sci. 2005;1056(1):206–217. doi: 10.1196/annals.1352.010.
    1. Aggarwal BB, Surh Y-J, Shishodia S. The molecular targets and therapeutic uses of curcumin in health and disease. Berlin: Springer; 2007.
    1. Baldwin AS. Series introduction: the transcription factor NF-κB and human disease. J Clin Investig. 2001;107(1):3–6. doi: 10.1172/JCI11891.
    1. Yuan J, Liu R, Ma Y, Zhang Z, Xie Z. Curcumin attenuates airway inflammation and airway remolding by inhibiting NF-κB signaling and COX-2 in cigarette smoke-induced COPD mice. Inflammation. 2018;41(5):1804–1814. doi: 10.1007/s10753-018-0823-6.
    1. Wong CK, Li ML, Wang CB, Ip WK, Tian YP, Lam CW. House dust mite allergen Der p 1 elevates the release of inflammatory cytokines and expression of adhesion molecules in co-culture of human eosinophils and bronchial epithelial cells. Int Immunol. 2006;18(8):1327–1335. doi: 10.1093/intimm/dxl065.
    1. Wuyts WA, Vanaudenaerde BM, Dupont LJ, Demedts MG, Verleden GM. Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-κB in IL-1β-induced chemokine release in human airway smooth muscle cells. Respir Med. 2003;97(7):811–817. doi: 10.1016/S0954-6111(03)00036-2.
    1. Kobayashi T, Hashimoto S, Horie T. Curcumin inhibition of Dermatophagoides farinea-induced interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF) production by lymphocytes from bronchial asthmatics. Biochem Pharmacol. 1997;54(7):819–824. doi: 10.1016/S0006-2952(97)00220-7.
    1. Ram A, Das M, Ghosh B. Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized guinea pigs. Biol Pharm Bull. 2003;26(7):1021–1024. doi: 10.1248/bpb.26.1021.
    1. Kim DH, Phillips JF, Lockey RF. Oral curcumin supplementation in patients with atopic asthma. Allergy Rhinol. 2011;2(2):ar-2011. doi: 10.2500/ar.2011.2.0016.
    1. Lelli D, Sahebkar A, Johnston TP, Pedone C. Curcumin use in pulmonary diseases: state of the art and future perspectives. Pharmacol Res. 2017;115:133–148. doi: 10.1016/j.phrs.2016.11.017.
    1. Oh S-W, Cha J-Y, Jung J-E, Chang B-C, Kwon H-J, Lee B-R, Kim D-Y. Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-κB inhibition. J Ethnopharmacol. 2011;136(3):414–421. doi: 10.1016/j.jep.2010.07.026.
    1. Liu L, Shang Y, Li M, Han X, Wang J, Wang J. Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor-E2-related factor 2/haem oxygenase (HO)-1 signalling pathway. Clin Exp Pharmacol Physiol. 2015;42(5):520–529. doi: 10.1111/1440-1681.12384.
    1. Baum L, Lam CWK. Cheung SK-K, Kwok T, Lui V, Tsoh J, Lam L, Leung V, Hui E, Ng C: Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol. 2008;28(1):110–113. doi: 10.1097/jcp.0b013e318160862c.
    1. Abidi A, Gupta S, Agarwal M, Bhalla H, Saluja M. Evaluation of efficacy of curcumin as an add-on therapy in patients of bronchial asthma. J Clin Diagn Res: JCDR. 2014;8(8):HC19.
    1. Hsieh C. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(2895):e2900.
    1. Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, Murray JJ, Pendergraft TB. Development of the asthma control test: a survey for assessing asthma control. Journal of Allergy and Clinical Immunology. 2004;113(1):59–65. doi: 10.1016/j.jaci.2003.09.008.
    1. Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ, Nathan RA, Kosinski M, Pendergraft TB, Jhingran P. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol. 2006;117(3):549–556. doi: 10.1016/j.jaci.2006.01.011.
    1. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–818. doi: 10.1021/mp700113r.
    1. Wang L, Li W, Cheng D, Guo Y, Wu R, Yin R, Li S, Kuo H-C, Hudlikar R, Yang H. Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats. J Pharmacokinet Pharmacodyn. 2020;47(2):131–144. doi: 10.1007/s10928-020-09675-3.
    1. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas P. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(04):353–356. doi: 10.1055/s-2006-957450.
    1. Srivastava K, Arora A, Kataria A, Cappelleri JC, Sadosky A, Peterson AM. Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis. Patient Prefer Adherence. 2013;7:419.
    1. Jagetia GC, Aggarwal BB. “Spicing up” of the immune system by curcumin. J Clin Immunol. 2007;27(1):19–35. doi: 10.1007/s10875-006-9066-7.
    1. Babaei F, Nassiri-Asl M, Hosseinzadeh H. Curcumin (a constituent of turmeric): New treatment option against COVID-19. Food Sci Nutr. 2020;8(10):5215–5227. doi: 10.1002/fsn3.1858.

Source: PubMed

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