TRIAL DESIGN: The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial.
PARTICIPANTS: All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan).
INTERVENTION AND COMPARATOR: In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan.
MAIN OUTCOMES: Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization.
RANDOMISATION: Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure.
BLINDING (MASKING): Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 1000 participants will be enrolled in the study with 1:1 allocation.
TRIAL STATUS: The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022.
TRIAL REGISTRATION: Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087 .
FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.
Methods: The TQ-PLGA NPs were prepared and characterized for size, zeta potential, encapsulation efficiency, and release profile.
Results: The particle size was 147.2 nm, with 22.1 positive zeta potential and 96.8% encapsulation efficiency. The NPs released 45.6% of the encapsulated TQ within 3 h followed by characteristic sustained release over 7 days with a total of 69.7% cumulative release. TQ-PLGA NPs were taken up effectively by the cells in a time-dependent manner up to 24 h. Higher cell toxicity was determined within the first 24 h in melanoma cells due to the rapid release of TQ from the NPs and its low stability in the cell culture media.
Conclusion: TQ-PLGA NPs is a potential anticancer agent taking advantage of the sustained release and tailored size that allows accumulation in the cancer tissue by the enhanced permeability and retention effect. However, stability problems of the active ingredient were address in this study and requires further investigation.
METHODS: A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT.
RESULTS: A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone.
CONCLUSION: Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.
METHODS: Twenty-four Dorper lambs (18.68±0.6 kg, 4 to 5 months old) were randomly assigned to a concentrate mixture containing either, no supplement (control, T1), 1% Rosmarinus officinalis leaves (T2), 1% Nigella sativa seeds (T3), or 1% Rosmarinus officinalis leaves+1% Nigella sativa seeds (T4) on a dry matter basis. The lambs were fed the treatments with urea-treated rice straw for 90 days, slaughtered and the muscles were subjected to a 7 d postmortem chill storage.
RESULTS: The T2 lambs had greater (p<0.05) slaughter and cold carcass weights than the control lambs. Dietary supplements did not affect (p>0.05) chill loss, dressing percentage, carcass composition, intramuscular fat and muscle pH in Dorper lambs. Meat from supplemented lambs had lower (p<0.05) cooking and drip losses, shear force, lightness, and lipid oxidation and greater (p<0.05) redness compared with the control meat. The impact of dietary supplements on muscle FA varied with muscle type. Diet had no effect (p>0.05) on the expression of stearoyl-CoA desaturase and lipoprotein lipase genes in LD and ST muscles in Dorper lambs. The T2 and T3 diets up regulated the expression of AMP-activated protein kinase alpha 2 gene in LD and ST muscles and up regulated the expression of sterol regulatory element-binding protein 1 in ST muscle in Dorper lambs.
CONCLUSION: Dietary supplementation of Nigella sativa seeds and Rosmarinus officinalis leaves had beneficial effects on meat quality in Dorper lambs.