A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2
Clinical Study Results
4. Materials and Methods
4.1. Clinical Study Design
4.3. Randomization and Masking
4.6. Statistical Analysis
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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|N (%)||N (%)||N (%)|
|Female||31 (56.36)||16 (55.17)||15 (57.69)|
|Male||24 (43.64)||13 (44.83)||11 (42.31)|
|Asian||Non-Hispanic/Latino||1 (1.82)||1 (3.45)|
|Black or African American||Hispanic/Latino||3 (5.45)||1 (3.45)||2 (7.69)|
|Non-Hispanic/Latino||4 (7.27)||1 (3.45)||3 (11.54)|
|White||Hispanic/Latino||20 (36.36)||11 (37.93)||9 (34.62)|
|Non-Hispanic/Latino||5 (9.09)||2 (6.9)||3 (11.54)|
|Others||Hispanic/Latino||22 (40.00)||13 (44.83)||9 (34.62)|
|Years (Mean ± SD)||45.69 ± 17.35||45.48 ± 19.29||45.92 ± 15.27|
|≤55 years||39 (70.91)||21 (72.41)||18 (69.23)|
|>55 years||16 (29.09)||8 (27.5)||8 (30.76)|
|Diabetes Mellitus 2||10 (18.18)||5 (17.24)||5 (19.23)|
|Hypertension||22 (40.00)||11 (37.93)||11 (42.31)|
|Underweight||1 (1.82)||1 (3.45)|
|Normal weight||9 (16.36)||2 (6.90)||7 (26.92)|
|Overweight||24 (43.64)||14 (48.28)||10 (38.46)|
|Obese||21 (38.18)||12 (41.38)||9 (34.62)|
|SARS-CoV-2 Vaccination *||9 (16.36)||7 (24.13)||2 (7.69)|
|Viral Load Day 0||Placebo||23||59||1683||25,000||25,000||25,000||15,418||11,465||0.69|
|Viral Load Day 7||Placebo||18||0||0||12,282||25,000||25,000||12,479||12,539||0.81|
|Viral Load Day 14||Placebo||19||0||0||0||25,000||25,000||9056||11,907||0.18|
|Objectives/Purpose||Endpoints/Outcome Measures||Justification and Results for Endpoints|
|To evaluate if treatment with 3 g TQ Formula (500 mg per capsule, 3 capsules BID) given orally on outpatient basis can significantly reduce median time-to-sustained-clinical-response compared to placebo in participants with COVID-19 infection treated in the outpatient setting.||Measurement of the difference in median time-to-sustained-clinical-response in participants taking 3 g TQ Formula (500 mg per capsule, 3 capsules BID) versus participants taking placebo. Sustained clinical response is defined as a reduction of scores to ≤2 on all symptoms of the Modified FLU-PRO Plus.||A reduction in time-to-sustained-clinical-response is a direct measure of treatment effectiveness.|
Results: median time-to-SCR of 6 days in TQ Formula arm (95% CI: 4.14) versus 8 days in placebo arm (95% CI: 6.11). (p = 0.77).
|To evaluate the safety and tolerability of TQ Formula (500 mg oral capsule, 3 capsules BID) when given to participants with COVID-19 infection.||Number of overall adverse events, related adverse reactions, and hospitalizations reported in participants taking 3 g TQ Formula (500 mg per capsule, 3 capsules BID) versus participants taking placebo. All AEs/SAEs will be captured throughout the study as per schedule of assessments.||Comparing the number of AEs and SAEs and any relationship to IP is important for determining the safety profile of TQ Formula.|
Results: TQF arm had no SAEs and had 50% less AE incidence compared to placebo while this difference was not significant (p = 0.16).
|To compare the viral load profile over time (from baseline through to day 14) between treatment with 3 g TQ Formula (500 mg per capsule, 3 capsules BID) given orally on outpatient basis and placebo in participants with COVID-19 infection.||Measurement of change in quantitative viral load from baseline, day 7, and day 14 using RT-PCR in participants taking 3 g TQ Formula (500 mg per capsule, 3 capsules BID) versus participants taking placebo with COVID-19 infection.||Faster decline in viral load is hypothesized to lead to faster recovery from the illness and less infectivity.|
Results: trend of a faster decline in viral load with TQ formula treatment (p = 0.146).
|To compare the percentage of RT-PCR negative/undetectable (i.e., viral clearance) on day 7 and day 14 in participants taking 3 g TQ Formula (500 mg per capsule, 3 capsules BID) versus participants taking placebo.||Percentage of negative/undetectable RT-PCR (i.e., viral clearance) on day 7 and day 14 in participants taking 3 g TQ Formula (500 mg per capsule, 3 capsules BID) versus participants taking placebo.||Treatment with 3 g TQ Formula (500 mg per capsule, 3 capsules BID) given orally on outpatient basis is hypothesized to result in higher percentages of viral clearance by RT-PCR|
Faster decline in viral load is hypothesized to lead to faster recovery from the illness and less infectivity.
Results: Lower percentage of RT-PCR positive cases in TQ Formula arm on day 14 (24% vs. 42%, p = 0.22).
|To compare the duration and severity of symptoms (measured by Modified FLU-PRO Plus) overtime from day 1 through day 14 in total Modified FLU-PRO Plus symptom severity score overall and in sub-domain scores (namely, Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, Taste/Smell), between treatment with 3 g TQ Formula (500 mg per capsule, 3 capsules BID) given orally on outpatient basis and placebo in participants with COVID-19 infection.||Measurement of severity of and change in COVID-19 symptoms per total score as well as sub-scores (Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, Taste/Smell) measured through Modified FLU-PRO Plus from day 1 through day 14 in participants with COVID-19 infection treated either with 3 g TQ Formula (500 mg per capsule, 3 capsules BID) or placebo.||FLU-PRO is a validated measure that has been used on multiple virus studies. The Modified FLU-PRO Plus version has additional questions (Taste/Smell) that are COVID-19 specific. The Modified FLU-PRO Plus has been shortened to reduce number of symptoms.|
Results: oral TQ Formula treated arm led to significantly faster decline in overall symptom burden from day 1 through day 14 as compared to placebo treated arm (p < 0.0001) as well as in throat (p = 0.0003), body/systemic (p = 0.0011),
Chest/Respiratory (p = 0.024), and Smell/Taste (p = 0.032) subdomains.
|To investigate if there exists an association between viral load and symptom severity by study arm and if such associations change overtime.||Correlation Coefficient of quantitative viral load and symptom severity at baseline, at day 7, and day 14 in participants taking 3 g TQ Formula (500 mg per capsule, 3 capsules BID) versus participants taking placebo||Decreases in viral load are hypothesized to be correlated with better clinical outcomes.|
Results: raw baseline Viral Load measure is negatively associated with total symptom burden (Spearman’s rank correlation = −0.30, p = 0.037). This negative rank-association does not remain significant on day 7 (p = 0.48) while show significance on day 14 (Spearman’s rank correlation = −0.46, p = 0.0031).
|To evaluate the basic pharmacokinetics of TQ Formula’s main active ingredient (thymoquinone) at same time points (Days 1, 7, and 14) in participants with COVID-19 infection.||Measurement of thymoquinone and metabolites’ concentration in the plasma on day 1, day 7 and 14 using HPLC in patients treated with TQ Formula.||Thymoquinone is the main active ingredient of TQ Formula and the pharmacokinetics of thymoquinone and its’ metabolites in the plasma of treated patients are used to correlate with effectiveness of treatment.|
Results: analysis ongoing.
|To explore the effect of TQ Formula on inflammatory cytokines, coagulation factors and effector immune cells at same time points (Days 1, 7, and 14) in participants with COVID-19 infection.||Measurement of the inflammatory cytokine production, coagulation factors and the various effector immune cell subsets in the Peripheral Blood Mononuclear Cells (PBMC) of these patients on day 1, day 7 and day 14 using FACS.||The inflammatory cytokines and immunological markers are of importance because of their correlation with disease severity in COVID-19.|
Results: Statistically significant increases in CD4 and CD8 T-cell Percentages on day 14 (p = 0.042 for both).
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Bencheqroun, H.; Ahmed, Y.; Kocak, M.; Villa, E.; Barrera, C.; Mohiuddin, M.; Fortunet, R.; Iyoha, E.; Bates, D.; Okpalor, C.; et al. A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2. Pathogens 2022, 11, 551. https://doi.org/10.3390/pathogens11050551
Bencheqroun H, Ahmed Y, Kocak M, Villa E, Barrera C, Mohiuddin M, Fortunet R, Iyoha E, Bates D, Okpalor C, et al. A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2. Pathogens. 2022; 11(5):551. https://doi.org/10.3390/pathogens11050551Chicago/Turabian Style
Bencheqroun, Hassan, Yasir Ahmed, Mehmet Kocak, Enrique Villa, Cesar Barrera, Mariya Mohiuddin, Raul Fortunet, Emmanuel Iyoha, Deborah Bates, Chinedu Okpalor, and et al. 2022. "A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2" Pathogens 11, no. 5: 551. https://doi.org/10.3390/pathogens11050551