Curcumin in Management of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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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.

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

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

Conditions
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COPD

Intervention / Treatment
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* Dietary Supplement: Curcumin therapy
* Other: Placebo
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 89 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
Interventional Model Description: 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: Curcumin therapy added to standard COPD care<br>Subjects will be given instructions to take 1 capsule twice daily for 90 days, 30 min before or 1 hour after meals, with a glass of water; if they develop upset stomach or diarrhea, then to take the medication with meals. This treatment will be in addition to the usual care that the hospital physician prescribe for them to treat the COPD. | Dietary Supplement: Curcumin therapy<br>* 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).<br>Other: Standard care<br>* The standard of care for COPD.<br>|
| Active Comparator: Active Comparator: Placebo with Standard COPD care<br>Subjects will be given instructions to take 1 capsule twice daily for 90 days, 30 min before or 1 hour after meals, with a glass of water; if they develop upset stomach or diarrhea, then to take the medication with meals. This treatment will be in addition to the usual care that the hospital physician prescribe for them to treat the COPD. | Other: Placebo<br>* 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.<br>Other: Standard care<br>* The standard of care for COPD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 |