Effects of curcumin-piperine co-supplementation on clinical signs, duration, severity, and inflammatory factors in patients with COVID-19: a structured summary of a study protocol for a randomised controlled trial

Abstract

Objectives This study aims to investigate the efficacy of curcumin-piperine co-supplementation on disease duration, severity and clinical symptoms, and inflammatory mediators in patients with coronavirus (COVID-19). Trial design This is a randomized, placebo-controlled, double-blind, parallel arm clinical trial. Participants All patients aged 20-75 years with the diagnosis of Covid-19 based on the PCR test. The exclusion criteria will include an age less than 20 and more than 75 years, current use of warfarin or other anticoagulant drugs, and the presence of sensitivity to herbal products such as turmeric and pepper. This study will be conducted in academic hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Intervention and comparator Fifty outpatients will be randomly allocated in a ratio of 1:1 to receive a capsule of curcumin-piperine containing 500 mg curcumin plus 5 mg piperine or matching placebo containing 505 mg maltodextrin twice a daily, after lunch and dinner, over a period of 2 weeks. Similarly, 50 inpatients who are admitted to hospital wards excluding intensive care unit (ICU) will be randomly assigned in a ratio of 1:1 to receive a capsule curcumin-piperine or matching placebo (provided by the Sami Labs company) twice a daily, after lunch and dinner, over a period of 2 weeks. Main outcomes The main outcomes of this study are the efficacy of curcumin-piperine on coronavirus disease’s clinical symptoms, duration, severity, and inflammatory mediators after 2 weeks of curcumin-piperine co-supplementation. Randomisation Randomization sequences will be generated with the use of a random-number table with a permuted block design (block size of 4) and stratification according to the gender variable (male vs. female). These sequences will be prepared by an independent statistician and will be kept in opaque, sealed, numbered envelopes which will be opened only at the time of enrollment. The allocation ratio in intervention and control groups is 1:1. Researchers and all patients will be unaware of the study-group assignment until the completion of data analyses. Blinding (masking) This study is a double-blind clinical trial (participant, researcher). The curcumin-piperine and placebo supplements are packaged in similar numbered drug containers, and the researcher and all patients will be unaware of the study assignment until the end of the study. Numbers to be randomised (sample size) The calculated total sample size is 100 patients, with 25 patients in each group. Trial Status The protocol is Version 2.0, May 24, 2020. Recruitment began May 4, 2020, and is anticipated to be completed by April 19, 2021. Trial registration This trial has been registered by the title of “Effect of curcumin-piperine co-supplementation on disease duration, severity and clinical signs, and inflammatory factors in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial study” in the Iranian Registry of Clinical Trials (IRCT) with code “IRCT20121216011763N46”, https://www.irct.ir/trial/47529. The registration date is May 4, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Plant Alkaloids Inhibit Membrane Fusion Mediated by Calcium and Fragments of MERS-CoV and SARS-CoV/SARS-CoV-2 Fusion Peptides

“…Moreover, to our knowledge, except for one bioassay with SARS-CoV-2-S pseudotyped particles [72], this is the first study demonstrating the in vitro activity of piperine against SARS-CoV-2 virus. It should be noted that piperine with curcumin is being studied in several clinical trials for the treatment of COVID-19 [73][74][75]. According to [75], administration of oral curcumin with piperine substantially reduced the morbidity and mortality due to COVID-19.…”

Metabolic Implications of Oxidative Stress and Inflammatory Process in SARS-CoV-2 Pathogenesis: Therapeutic Potential of Natural Antioxidants

“…Considering that the ACE-2 receptor is significantly expressed in nasal cells and mucosal cells of the respiratory tract, an emulsion of topically applied curcumin as an adjuvant therapy for COVID-19 has been proposed (Manoharan et al, 2020). An ongoing randomized controlled trial of a capsule containing 500 mg curcumin and 5 mg piperine is being administered to COVID-19 patients to determine possible therapeutic effects on disease severity and inflammatory mediators in the study subjects (Miryan et al, 2020) Quercetin is a plant flavonoid with reported antioxidant, antiinflammatory and antiviral effects (Colunga Biancatelli et al, 2020).…”

Ayurveda Rasayana as antivirals and immunomodulators: potential applications in COVID-19

“…A randomized, pen label exploratory trial is registered in India for the evaluation of safety and efficacy of T. cordifolia + P. longum as adjunct treatment to standard care for the management of mild to moderate COVID-19 patients (CTRI/2020/06/025557). A similar kind of randomized double-blind placebo-controlled trial to evaluate the effect of curcumin-piperine in SARS-CoV-2 patients in Iran is also ongoing (Miryan et al 2020 ). Acute toxicity studies of P. longum show no mortality or morbidity when 3 to 5g/kg is administered to animals during pharmacological studies; however, under certain conditions, such as pregnancy and lactation, the fruits of P. longum should be used with caution due to potential interactions (Chanda et al 2009 ).…”