A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2

Abstract

There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study’s aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.

Thymoquinone Plus Immunotherapy in Extra-Pulmonary Neuroendocrine Carcinoma: Case Series for a Novel Combination

“…The three doses of BSO were well tolerated, with only three subjects experiencing mild epigastric discomfort that settled down after taking the capsules after meals. Recently, a randomized phase II trial in COVID patients compared adverse events for patients who took TQ (3 g per day) or a placebo, and the results indicated that TQ was safe and tolerable [ 47 ]. Our four patients took only three tablets of 500 mg per day with no documented side effects, which is correlated with these previous data.…”

Dietary phytochemicals against COVID‐19: A focus on thymoquinone

“…There was no significant difference in the rate of adverse events ( p = 0.16), indicating its safety, which is consistent with a previous Phase 1 study (Thomas et al, 2022). TQF significantly improved the total symptom burden faster ( p < 0.001), and increased cytotoxic CD4 + ( p = 0.04) and helper CD8 + ( p = 0.04) central memory T lymphocytes (Bencheqroun et al, 2022).…”

“…TQ shows relatively high cytotoxicity in in vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/ 2020) (Abdallah et al, 2022). TQ inhibits four further SARS-CoV-2 variants (Omicron, 614D, Delta, UK, Brazil) in infection of HEK293-ACE2 cells with an IC 50 value range between 1 and 3 µM (Bencheqroun et al, 2022). Compared with IC 50 of Nirmatrelvir at the nanomolar range (Rosales et al, 2022), these values seem F I G U R E 1 Chemical structures of anti-SARS-CoV-2 thymoquinone from Nigella sativa and other phytochemicals.…”

“…Also, only single doses of these products were used. It would be good to carry out future clinical trials using standardized products by quantifying TQ content in the N. sativa extract or oils (Bencheqroun et al, 2022; Johnson‐Ajinwo & Li, 2014) or even use the pure TQ formulation at different doses with a larger number of patients in a randomized, double‐blind, and placebo‐controlled manner (Bencheqroun et al, 2022). Considering the benefits of honey in managing COVID‐19, the preparation of a combination of honey with N. sativa oil with a determined quantity of TQ is also recommended for future clinical investigation against COVID‐19 or other diseases.…”

Black Seeds

“…These trials examined suppression of Helicobacter pylori infections and dyspepsia, [147][148][149][150][151] parasitic, bacterial and human immunodeficiency virus infections, [152][153][154][155][156][157] hepatitis C symptoms, 158,159 and Candida albicans-induced vaginitis. 160 Other initial findings suggest that NS oil 161 and TQ 162 have potential to relieve SARS-2-COVID symptoms. 163,164 In addition, NS was evaluated for treating skin disorders, [165][166][167][168][169][170] for alleviating diverse oral health problems, [171][172][173][174][175][176][177][178] and for relieving menstrual-and menopausal-related symptoms.…”