Curcumin in Management of Chronic Obstructive Pulmonary Disease

COPD Clinical Trial

Official title:

Curcumin in Management of Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial (C-COPD Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04687449
• Other study ID #: 19-1603
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: December 15, 2023

Study information

• Verified date: July 2021
• Source: Danbury Hospital
• Contact: Rakhee Agarwal, PhD
• Phone: 203-739-4932
• Email: rakhee.agarwal[@]nuvancehealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this double-blind, placebo-controlled trial, 120 patients with a diagnosis of COPD will be randomized to receive either a daily curcumin preparation or placebo for 90 days, in addition to the standard of care treatment. The outcomes will be compared between the study arms. No dose escalation will be used.

Description:

Chronic obstructive pulmonary disease (COPD) kills more than 3 million people worldwide every year. COPD is managed mainly by pharmacological therapy during the stable stage. Research illustrates many proven beneficial outcomes associated with the use of bronchodilators (beta-agonists and anticholinergics), inhaled and oral steroids to decrease the bronchial tree inflammation, some antibiotics, such as azithromycin, which have not only antibacterial but also some anti-inflammatory properties. However, these remedies have many limitations due to the development of adverse effects and resistance. Despite the treatment, symptoms related to COPD negatively affect patients' quality of life and limit their essential physical abilities, such as walking.

Although achievements have been made in the management of COPD, exacerbation (worsening or flare up) remains a leading cause for hospital admission. COPD exacerbation adversely affects patients' quality of and creates a significant financial burden on the healthcare system nationally and on a local level. Hospitals with excess readmission ratios for COPD are penalized financially by the Centers for Medicare and Medicaid Services. In Danbury Hospital, about 15% of patients admitted for COPD exacerbation are readmitted within 30 days on average.

Therefore, there is an urgent need for continued development of maintenance drugs for the treatment of COPD. Aside from the ordinary accepted pharmacological therapy approved for treatment of this chronic respiratory illness, some alternatives have pharmacologic properties that may potentially target the pathophysiologic processes involved in COPD.

Curcumin, a well-known polyphenol, is an active component of a plant Curcuma longa, commonly known as turmeric. Turmeric has been used for centuries as a spice and has recently become a widely used dietary supplement. Curcumin is reported to have anti-inflammatory properties by inhibiting NF-κB activation and IL-8,4,5 which are known to promote white blood cell activity and expression of COX-2 (enzyme responsible for production of inflammatory cytokines) involved in the pathophysiology of COPD. It has also been associated with the inhibition of cigarette smoke-induced NF-κB activation in bronchial epithelium in mice; in addition, it has been shown to revitalize steroid response in human cells.

The data on the effects of curcumin on inflammatory cytokines, as described above, has been derived from in vitro cell line and animal studies. While curcumin has been studied in humans for other inflammatory conditions (arthritis, gastrointestinal conditions, etc) to our knowledge, no human studies to explore its role in the management of COPD are available. As bronchial inflammation plays a key role in pathophysiology of COPD and curcumin has been shown to exhibit significant anti-inflammatory properties, we hypothesize that use of curcumin is associated with improvement in outcomes in patients with COPD.

Primary objective

1. To study if daily oral consumption of a curcumin preparation is associated with decreased health impairment in patients with COPD.

Secondary objectives

1. To study if daily oral consumption of a curcumin preparation is associated with improved functional exercise capacity among patients with COPD.

2. To study if daily oral consumption of a curcumin preparation is associated with decreased risk of an acute COPD exacerbation, and related hospital admission, in patients with COPD.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 15, 2023
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 89 Years

Eligibility

Inclusion Criteria:

• Provision of signed and dated informed consent form by the subject.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Clinical diagnosis of COPD, defined as having a smoking history of at least 10 pack-years, a ratio of post bronchodilator forced expiratory volume in 1 second [FEV1] to forced vital capacity of <70%, and a post bronchodilator FEV1 of <80% of the predicted value.

• Patient has not had an acute exacerbation of COPD for at least 4 weeks of time of screening.

Exclusion Criteria:

• Known allergic reactions to components of the study medication

• Use of turmeric as a spice or a dietary supplement within 3 months prior to enrollment

• Treatment with another investigational drug or other intervention at the time of enrollment

• Pregnancy or lactation

• Treatment with any chemotherapy agent, tacrolimus, talinolol, or sulfasalazine (due to the potential drug-drug interactions) at the time of enrolment

• Short-term steroid course received, for any reason, within 4 weeks prior to enrollment

• SGRQ-C is not available on the language preferred by the patient

• Patient is not able to undergo 6-minute walk due to a non-COPD related reason

Related Conditions & MeSH terms

• COPD
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Dietary Supplement:
• Curcumin therapy
Clear capsules (made of vegetable cellulose) with turmeric extract (500 mg, 95% curcuminoids), Bioperine (5 mg, improves absorption), and inactive ingredients (microcrystalline cellulose, vegetable magnesium stearate, silicon dioxide).

Other:
• Placebo
Clear capsules (made of vegetable cellulose) with inactive ingredients (lactose monohydrate and food color); the capsules will be matched in size and color of the content to the preparation used in the Curcumin capsule.
• Standard care
The standard of care for COPD.

Locations

Country	Name	City	State
United States	Pulmonary and Sleep Medicine clinic	Danbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Danbury Hospital

Country where clinical trial is conducted

United States, 

References & Publications (16)

ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. Erratum in: Am J Respir Crit Care Med. 2016 May 15;193(10):1185. — View Citation

Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016 Aug;19(8):717-29. doi: 10.1089/jmf.2016.3705. Review. — View Citation

Fung FY, Wong WH, Ang SK, Koh HL, Kun MC, Lee LH, Li X, Ng HJ, Tan CW, Zhao Y, Linn YC. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017 Aug 15;32:88-96. doi: 10.1016/j.phymed.2017.04.004. Epub 2017 Apr 10. — View Citation

Jones PW. Interpreting thresholds for a clinically significant change in health status in asthma and COPD. Eur Respir J. 2002 Mar;19(3):398-404. Review. — View Citation

Liu AC, Zhao LX, Lou HX. Curcumin alters the pharmacokinetics of warfarin and clopidogrel in Wistar rats but has no effect on anticoagulation or antiplatelet aggregation. Planta Med. 2013 Jul;79(11):971-7. doi: 10.1055/s-0032-1328652. Epub 2013 Jun 27. — View Citation

Miravitlles M, Ribera A. Understanding the impact of symptoms on the burden of COPD. Respir Res. 2017 Apr 21;18(1):67. doi: 10.1186/s12931-017-0548-3. Review. — View Citation

Rabe KF, Watz H. Chronic obstructive pulmonary disease. Lancet. 2017 May 13;389(10082):1931-1940. doi: 10.1016/S0140-6736(17)31222-9. Epub 2017 May 11. Review. — View Citation

Rennard S, Thomashow B, Crapo J, Yawn B, McIvor A, Cerreta S, Walsh J, Mannino D. Introducing the COPD Foundation Guide for Diagnosis and Management of COPD, recommendations of the COPD Foundation. COPD. 2013 Jun;10(3):378-89. doi: 10.3109/15412555.2013.801309. — View Citation

Shah T, Churpek MM, Coca Perraillon M, Konetzka RT. Understanding why patients with COPD get readmitted: a large national study to delineate the Medicare population for the readmissions penalty expansion. Chest. 2015 May;147(5):1219-1226. doi: 10.1378/chest.14-2181. — View Citation

Shishodia S, Potdar P, Gairola CG, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis. 2003 Jul;24(7):1269-79. Epub 2003 May 9. — View Citation

Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Criner GJ, Frith P, Halpin DMG, Han M, López Varela MV, Martinez F, Montes de Oca M, Papi A, Pavord ID, Roche N, Sin DD, Stockley R, Vestbo J, Wedzicha JA, Vogelmeier C. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019 May 18;53(5). pii: 1900164. doi: 10.1183/13993003.00164-2019. Print 2019 May. Review. — View Citation

Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest. 2001 Jan;119(1):256-70. Review. — View Citation

Suzuki M, Betsuyaku T, Ito Y, Nagai K, Odajima N, Moriyama C, Nasuhara Y, Nishimura M. Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice. Am J Physiol Lung Cell Mol Physiol. 2009 Apr;296(4):L614-23. doi: 10.1152/ajplung.90443.2008. Epub 2009 Jan 23. — View Citation

Vecchi Brumatti L, Marcuzzi A, Tricarico PM, Zanin V, Girardelli M, Bianco AM. Curcumin and inflammatory bowel disease: potential and limits of innovative treatments. Molecules. 2014 Dec 16;19(12):21127-53. doi: 10.3390/molecules191221127. Review. — View Citation

Yuan J, Liu R, Ma Y, Zhang Z, Xie Z. Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF-?B Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice. Inflammation. 2018 Oct;41(5):1804-1814. doi: 10.1007/s10753-018-0823-6. — View Citation

Zhang M, Xie Y, Yan R, Shan H, Tang J, Cai Y, Yin J, Chen M, Zhang J, Yang X, Zhang Q, Li Y. Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease. Life Sci. 2016 Nov 1;164:1-8. doi: 10.1016/j.lfs.2016.09.001. Epub 2016 Sep 4. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	St. George's Respiratory Questionnaire (SGRQ-C) score	Change in the 40-item version of the St. George's Respiratory Questionnaire (SGRQ-C) score: the score will be measured upon enrollment and at 90 days. It consists of 40 questions, and scored on 0 (no health impairment) to 100 (maximum health impairment) scale. The threshold for a clinically significant difference between groups of patients and for changes within groups of patients is four units.	Day 0 and 90
Secondary	Performance on the 6-minute walk test (6MWT)	Change in the 6-minute walk test (6MWT) result (in meters): the test will be administered upon enrollment and at 90 days.	Day 0 and 90
Secondary	Time to the first acute exacerbation of COPD	Difference in the time from initiation of the study medication to the first acute COPD exacerbation. Participants will be contacted over the phone 6 months after taking the first dose of the study medication, to inquire about outpatient and inpatient encounters for acute worsening of COPD occurred after the 90-day follow-up appointment; the participants' medical records will also be reviewed to determine if the reported encounters occurred due to acute COPD exacerbation as diagnosed by a medical provider and also to determine if COPD exacerbation occurred in those participants who could not be reached over the phone.	6 months
Secondary	Relative risk of the acute COPD exacerbation	Relative risk of the acute COPD exacerbation occurred during the study will be analyzed descriptively by calculating average occurrence (number of incidences in population over the 6-month period) in both study groups. Participants will be contacted over the phone 6 months after taking the first dose of the study medication, to inquire about outpatient and inpatient encounters for acute worsening of COPD occurred after the 90-day follow-up appointment; the participants' medical records will also be reviewed to determine if the reported encounters occurred due to acute COPD exacerbation as diagnosed by a medical provider and also to determine if COPD exacerbation occurred in those participants who could not be reached over the phone.	6 months
Secondary	Relative risk of hospital admission for acute COPD exacerbation.	Relative risk of hospital admission for acute COPD exacerbation occurred during the study will be analyzed descriptively by calculating average occurrence (number of incidences in population over the 6-month period) in both study groups. Participants will be contacted over the phone 6 months after taking the first dose of the study medication, to inquire about outpatient and inpatient encounters for acute worsening of COPD occurred after the 90-day follow-up appointment; the participants' medical records will also be reviewed to determine if the reported encounters occurred due to acute COPD exacerbation as diagnosed by a medical provider and also to determine if COPD exacerbation occurred in those participants who could not be reached over the phone.	6 months