Triple-blind Placebo-controlled Clinical Trial Research Articles

The effect of chamomile on flatulence after the laparoscopic cholecystectomy: A randomized triple-blind placebo-controlled clinical trial

ObjectiveFlatulence is one of the main post-operative Ileus-related complications, especially in abdominal surgeries, which can be largely due to the effects of anesthesia. There are various kinds of therapeutic methods used for their treatment though sometimes their effects are limited. Thus, it is essential to find alternative treatments to decrease the implications of the disease. The present study is aimed to investigate the effect of Chamomilla recutita on flatulence after Laparoscopic cholecystectomy. MethodsThis randomized controlled trial was carried out in 2020 at Isfahan in Iran. Patients randomly fell into either chamomile (n = 32) or placebo groups (n = 32). The intervention was performed 1 h before the operation. The severity and the frequency of flatulence were recorded using a visual analog scale in both groups in three stages before the operation, after the operation in recovery, and 2 h after the operation. ResultsThe flatulence was not observed before the operation and on arrival in the recovery room. Before leaving the recovery room, the frequency of flatulence was the same in both the groups. However, in the surgical ward, the frequency of flatulence in the chamomile group was significantly lower than in the placebo group. The mean of flatulence severity has significantly increased in both groups over time but in the chamomile group, this increase was significantly lower than in the placebo group. ConclusionThese results suggest that chamomile has a potential therapeutic effect on the gastrointestinal and can reduce flatulence. In laparoscopic surgeries, using chamomile drops as a preventive drug seems to be effective in reducing the incidence of postoperative flatulence.

Effect of MS14® on physical activity of multiple sclerosis patients: A randomized triple-blind placebo-controlled clinical trial.

Multiple Sclerosis (MS) is a neurological disorder with an increasing global prevalence and severe complications. MS14® is a Persian-medicine-derived natural product with herbal and marine origin which has shown beneficial effects in the management of MS complications. In this study, its effect on physical activity of MS patients was investigated. A triple-blind placebo-controlled clinical trial was conducted. Participants used either MS14 capsule or placebo 3 times a day for 3 weeks. At baseline and end of the study, physical activity indices were assessed using international physical activity questionnaire (IPAQ). Secondary outcome measures were Fatigue Severity Scale (FSS), timed 10m walk, Ashworth scale, and Timed Get up and Go. A total number of 80 MS patients completed the study. At the end of study, improvement of general physical activity (p-value=0.047) and Timed 10m walk index (p-value=0.003) in the MS14 group was significant when compared to placebo. No serious adverse effects were observed in this study. Considering the improvement of some physical activity indices, MS14® is seems to be a safe natural product which could be considered as a supplementary treatment in MS patients. Future larger trials are suggested to further evaluate its efficacy.

Alpha-Lipoic Acid Ameliorates Sperm DNA Damage and Chromatin Integrity in Men with High DNA Damage: A Triple Blind Randomized Clinical Trial.

Evidence suggests the contributory role of oxidative stress (OS) to sperm DNA damage and eventually, male infertility. Antioxidant supplementation has exhibited favorable results regarding seminal OS, sperm DNA damage, and chromatin integrity. We aimed to evaluate the effect of alpha-lipoic acid (ALA) supplementation on semen analysis, sperm DNA damage, chromatin integrity, and seminal/intracellular OS in infertile men with high sperm DNA damage. In this randomized triple-blind placebo-controlled clinical trial study, we opted for a triple-blind controlled clinical trial design. Considering the study's inclusion criteria for the level of sperm DNA fragmentation (higher than the threshold of 30 and 15%), 70% of participants were selected for this clinical research study. Subjects were divided into case and control groups receiving oral ALA (600 mg/day) and placebo for eighty days, respectively. Sperm parameters and functional tests were examined and compared before and after treatment. The final sample size was 34 and 29 for ALA and placebo receivers, respectively. No significant differences were observed about anthropometrics and baseline measures of semen analysis, DNA damage, OS, and chromatin integrity between the two groups. Conventional semen parameters were enhanced insignificantly in both groups (P>0.05). DNA damage decreased significantly in the ALA group, as per sperm chromatin structure assay (SCSA, P<0.001). Moreover, chromomycin A3 (CMA3) staining results indicated a decrease in nuclear protamine deficiency post-ALA therapy (P=0.004). Lipid peroxidation decreased significantly after treatment with ALA (P=0.003). Further, seminal antioxidant capacity/activity did not differ significantly in either of the groups (registration number: IRCT20190406043177N1). An 80-day course of oral ALA supplementation (600 mg/day) alleviates sperm OS, DNA damage, and chromatin integrity in men with high sperm DNA damage.

Curcumin and vitamin E improve hot flashes, lipid profile, and fasting blood glucose without any detrimental effect on the liver and renal function in postmenopausal women: A triple-blind placebo-controlled clinical trial

We conducted this study to evaluate the efficacy of Curcumin and vitamin E on hot flashes, lipid profile, blood glucose, and hepatic & renal biomarkers. Eighty-four postmenopausal women were randomly assigned into three groups to receive one Curcumin 500 milligram, vitamin E 200 IU, or placebo capsules twice/daily/eight weeks. In comparison with placebo, vitamin E significantly decreased the number of hot flashes (P = 0.002), serum triglyceride (P < 0.001), and aspartate aminotransferase (P = 0.007), while it increased high-density lipoprotein cholesterol (P = 0.005). Curcumin decreased significantly fasting blood glucose (P = 0.007), total cholesterol (P = 0.015), and triglyceride (P = 0.007) compared to placebo. We conclude that vitamin E reduced the incidence of hot flashes by nearly one-third of the base amount. It improved serum lipid profile and aspartate aminotransferase. Curcumin ameliorated fasting blood glucose and serum lipid profile.

The effects of licorice mucoadhesive patches (Aftogel®) on the results of nasopharyngeal swab real-time PCR test of SARS-CoV-2: a randomized triple-blind placebo-controlled clinical trial

Background and objectives: Up to present no efficacious antiviral medications have been discovered in order to eradicate SARS-CoV-2 in nasopharyngeal tract. In this article, the aim is to evaluate the effectiveness of a new herbal drug product called Aftogel patch, which contains licorice extract, in the eradication of this novel coronavirus in the nasopharyngeal secretions of the patients. Methods: In this triple-blind randomized clinical trial, 125 patients with positive real-time PCR for SARS-CoV-2 and in stage 0 and/or 1 of COVID-19 were studied in two separate groups, namely interventional and placebo, in which they used Aftogel and placebo patches, respectively. At the end of the study, the results of PCR test in aforementioned groups were assessed and compared. Results: Following the application of Aftogel, Real-time PCR was converted to negative in 53.97% of patients which was significantly higher than that of the placebo groups. (27.40%, P= 0.003). Conclusion: It seems that Aftogel mucoadhesive patch (Licorice extract) is effective in the eradication of SARS-CoV-2 which has colonized the nasopharyngeal area. Hence, this drug product has the potential for evaluation as a prophylactic agent against COVID-19.

The Effect of Spirulina on Anxiety in Patients with Hypertension: A Randomized Triple-Blind Placebo-Controlled Clinical Trial

Background: High blood pressure, coronary heart disease (CHD), and anxiety ailments entirely lead to many illness in patients and impose expenses on the health care system. Anxiety can significantly predict future CHD consequences. Spirulina is a known antioxidant that has a role in anxiety. The hypothesis was that Spirulina could alleviate anxiety and positively affect hypertension and its consequences. Nonetheless, there are scarce recently developed investigations on assessing the effect of consuming Spirulina on anxiety in human beings. Methods: The present study assessed the effect of Spirulina on anxiety in 48 Iranian patients with hypertension (female and male) aged 24–65 years in a randomized triple-blind, placebo-controlled clinical trial. The patients were given either 2 g Spirulina in the form of spirulina-fortified dressing or placebo. Anxiety levels were evaluated for each patient before and after eight weeks following consumption products with the Beck Anxiety Inventory. Results: Forty-one participants completed the intervention. At the baseline, there was no significant difference in anxiety levels between groups, and they also had the same levels of stress based on the Holmes-Rahe questionnaire. The results showed no significant difference in the level of anxiety between groups after the intervention (P = 0.93). Conclusion: Although no positive results were seen in this study, this novel issue has a potential for further investigations to make comprehensive decisions.

The effect of caffeine on tinnitus: Randomized triple-blind placebo-controlled clinical trial.

To test the hypothesis that caffeine can influence tinnitus, we recruited 80 patients with chronic tinnitus and randomly allocated them into two groups (caffeine and placebo) to analyze the self-perception of tinnitus symptoms after caffeine consumption, assuming that this is an adequate sample for generalization. The participants were randomized into two groups: one group was administered a 300-mg capsule of caffeine, and the other group was given a placebo capsule (cornstarch). A diet that restricted caffeine consumption for 24 hours was implemented. The participants answered questionnaires (the Tinnitus Handicap Inventory-THI, the Visual Analog Scale-VAS, the profile of mood state-POMS) and underwent examinations (tonal and high frequency audiometry, acufenometry (frequency measure; intensity measure and the minimum level of tinnitus masking), transient otoacoustic emissions-TEOAE and distortion product otoacoustic emissions-DPOAE assessments) at two timepoints: at baseline and after capsule ingestion. There was a significant change in mood (measured by the POMS) after caffeine consumption. The THI and VAS scores were improved at the second timepoint in both groups. The audiometry assessment showed a significant difference in some frequencies between baseline and follow-up measurements in both groups, but these differences were not clinically relevant. Similar findings were observed for the amplitude and signal-to-noise ratio in the TEOAE and DPOAE measurements. Caffeine (300 mg) did not significantly alter the psychoacoustic measures, electroacoustic measures or the tinnitus-related degree of discomfort.

The Effect of Combined Vitamin C and Vitamin E Supplementation on Oxidative Stress Markers in Women with Endometriosis: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial.

Background Endometriosis is a chronic and estrogen-dependent pelvic inflammatory disease, which may have various causes, such as oxidative stress. Dysmenorrhea, dyspareunia, and pelvic pain are well-known symptoms of endometriosis. The present clinical trial assessed the role of supplementation with antioxidant vitamins on the indices of oxidative stress as well as the severity of pain in women with endometriosis. Materials and Methods We enrolled 60 reproductive-aged (15–45 years) women with pelvic pain in this triple-blind clinical trial. They had 1–3 stages of laparoscopic-proven endometriosis. The participants were randomized to group A (n = 30), given vitamin C (1000 mg/day, 2 tablets of 500 mg each) and vitamin E (800 IU/day, 2 tablets of 400 IU each) combination, or group B (n = 30), given placebo pills daily for 8 weeks. Results Following treatment with vitamin C and vitamin E, we found a significant reduction in MDA and ROS compared with the placebo group. There was no significant decline in total antioxidant capacity after treatment. However, the severity of pelvic pain (p value <0.001), dysmenorrhea (p value <0.001), and dyspareunia (p value <0.001) significantly decreased in the treatment group after 8 weeks of supplementation. Conclusions The present findings support the potential role of antioxidants in the management of endometriosis. The intake of vitamin C and vitamin E supplements effectively reduced dysmenorrhea severity and improved dyspareunia and severity of pelvic pain.

Preoperative β-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial.

The majority of deaths from breast cancer occur following the development of metastatic disease, a process inhibited by β-blockers in preclinical studies. This phase II randomized controlled trial evaluated the effect of preoperative β-blockade with propranolol on biomarkers of metastatic potential and the immune cell profile within the primary tumor of patients with breast cancer. In this triple-blind placebo-controlled clinical trial, 60 patients were randomly assigned to receive an escalating dose of oral propranolol (n = 30; 80-160 mg daily) or placebo (n = 30) for 7 days prior to surgery. The primary endpoint investigated the effect of propranolol on prometastatic and proinflammatory gene expression within the primary tumor. Propranolol downregulated primary tumor expression of mesenchymal genes (P = 0.002) without affecting epithelial gene expression (P = 0.21). Bioinformatic analyses implicated downregulation of Snail/Slug (P = 0.03), NF-κB/Rel (P < 0.01), and AP-1 (P < 0.01) transcription factors in structuring the observed transcriptome alterations, and identified changes in intratumoral neutrophil, natural killer cell, and dendritic cell recruitment (all P < 0.01). Patients with clinical evidence of drug response (lowered heart rate and blood pressure) demonstrated elevated tumor infiltration of CD68+ macrophages and CD8+ T cells. One week of β-blockade with propranolol reduced intratumoral mesenchymal polarization and promoted immune cell infiltration in early-stage surgically-resectable breast cancer. These results show that β-blockade reduces biomarkers associated with metastatic potential, and support the need for larger phase III clinical trials powered to detect the impact of β-blockade on cancer recurrence and survival.See related commentary by Blaes et al., p. 1781.

The efficacy of topical red clover oil on knee osteoarthritis: A pilot prospective randomized triple-blind placebo-controlled clinical trial.

A triple-blind placebo-controlled clinical trial was performed to evaluate the efficacy of topical red clover oil (containing standardized red clover extract in olive oil) on knee osteoarthritis (OA). A total of 80 patients, 50-80 years old, with primary knee OA were randomly allocated to two groups. The study group used topical red clover oil and the control group used olive oil for 4 weeks (20 drops twice a day). Both groups adhered to nonpharmacological American College of Rheumatology recommendations and took meloxicam tablets during the study (0-8 weeks), and were followed up from Week 4 to 8. Efficacy measures were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale and Visual Analogue Scale (VAS). At baseline, both groups were homogeneous regarding demographic characteristics. In addition, they were asked about the side effects during the intervention. The results showed that the WOMAC score and its subscales of pain and stiffness and function scores and VAS significantly increased over time in both groups (p < .001). The study group showed a significant increase regarding pain (p = .001), function (p = .010), VAS (p < .001), and the WOMAC total score (p = .018). No serious drug side effects were observed. Red clover oil may have positive effects on symptoms of knee OA and can be considered as a complementary treatment.

Effect of chamomile on chemotherapy-induced neutropenia in pediatric leukemia patients: A randomized triple-blind placebo-controlled clinical trial.

Chemotherapy-induced neutropenia is one of the main side effects of acute lymphoblastic leukemia (ALL) treatment. In this trial, we evaluated the efficacy of chamomile in management of neutropenia. This randomized triple-blind placebo-controlled clinical trial was carried out in 2-18-year-old children with ALL. Participants in each group daily received 2.5 ml of either chamomile syrup or placebo syrup for a period of 30 days. Participants' white blood cell (WBC), and absolute neutrophil count (ANC), as well as their quality of life were evaluated. The study was completed with a total of 40 patients. An increasing trend of ANC was observed in the treatment group despite the decreasing trend in placebo group, which was statistically significant between the two groups (P Interaction=0.019, 95% confidence intervals=15.076-171.324). No serious side effects were reported. Using chamomile syrup as a complementary therapy in children with leukemia could improve their immunity (as it increased WBC) by minimizing chemotherapy-induced neutropenia.

Effects of Vitamin D Supplementation on Recurrence of Nasal Polyposis after Endoscopic Sinus Surgery.

Introduction:Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a relatively common disease with serious impacts on patient quality of life. Recurrence of polyps after functional endoscopic sinus surgery (FESS) is a dilemma. Vitamin D3 (VD3) is known to inhibit the proliferation of nasal polyp-derived fibroblasts. The present study aimed to investigate the effects of oral VD3 on the recurrence of polyposis after FESS. Materials and Methods:This triple-blind placebo-controlled clinical trial was conducted on 40 patients with CRSwNP who did not respond to medical treatment and were candidates for FESS. In addition, the patients had VD3 insufficiency. Following the surgery, all the patients received routine treatment (i.e., fluticasone spray, irrigation, cefixime 400 mg daily for 10 days, and montelukast for a month). Moreover, the case group received oral VD3 tablets 4000 IU (single daily dose) for a month, and the control group received placebo in the same manner. The Sino-Nasal Outcome Test (SNOT-22) and Meltzer endoscopic grading scores were recorded at months 1, 3, and 6 after the study. Results:In this study, 6 months following the intervention, the severity of polyposis was reported to be significantly lower in the VD3 group compared to the placebo group based on SNOT-22 (16.25±10.16 in the VD3 group vs. 47.45±13.55 in the placebo group; P<0.001) and Meltzer scores (0.50±0.60 in the VD3 group vs. 2.65±0.93 in the placebo group; P<0.001). No adverse effects were observed in the case group. Conclusion:This study showed the efficacy and safety of vitamin D supplementation in the reduction of polyposis recurrence after FESS in patients with CRSwNP.