A randomized double-blind placebo-controlled crossover trial of sodium nitrate in patients with stable angina INAS.
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SUBMITTER: Schwarz K
PROVIDER: S-EPMC5097453 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
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A randomized double-blind placebo-controlled crossover trial of sodium nitrate in patients with stable angina INAS.
Schwarz Konstantin K Singh Satnam S Parasuraman Satish Kumar SK Bruce Maggie M Shepstone Lee L Feelisch Martin M Minnion Magdalena M Ahmad Shakil S Horowitz John J Dawson Dana K DK Frenneaux Michael P MP
Future cardiology 20161012 6
In an aging western population, a significant number of patients continue to suffer from angina once all revascularization and optimal medical treatment options are exhausted. Under experimental conditions, oral supplementation with inorganic nitrate was shown to exhibit a blood pressure-lowering effect, and has also been shown to promote angiogenesis, improve endothelial dysfunction and mitochondrial efficiency in skeletal muscle. It is unknown whether similar changes occur in cardiac muscle. I ...[more]
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Project description:In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina.Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P=0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P=0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] ?mol/L, P<0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P=0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation.Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication.URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17.
| S-EPMC5634294 | biostudies-literature
Project description:INTRODUCTION:The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in patients with heart disease is stent implantation in the diseased coronary artery. While this procedure has revolutionised treatment, the incidence of secondary events remains a concern. These repeat events are thought to be due, in part, to continued enhanced platelet reactivity, endothelial dysfunction and ultimately restenosis of the stented artery. In this study, we will investigate whether a once a day inorganic nitrate administration might favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis. METHODS AND DESIGN:NITRATE-OCT is a double-blind, randomised, single-centre, placebo-controlled phase II trial that will enrol 246 patients with stable angina due to have elective percutaneous coronary intervention procedure with stent implantation. Patients will be randomised to receive 6?months of a once a day dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo) starting up to 1?week before their procedure. The primary outcome is reduction of in-stent late loss assessed by quantitative coronary angiography and optical coherence tomography at 6?months. The study is powered to detect a 0.22±0.55?mm reduction in late loss in the treatment group compared with the placebo group. Secondary end points include change from baseline assessment of endothelial function measured using flow-mediated dilation at 6?months, target vessel revascularisation (TVR), restenosis rate (diameter>50%) and in-segment late loss at 6?months, markers of inflammation and platelet reactivity and major adverse cardiac events (ie, myocardial infarction, death, cerebrovascular accident, TVR) at 12 and 24?months. ETHICS AND DISSEMINATION:The study was approved by the Local Ethics Committee (15/LO/0555). Trial results will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals. TRIAL REGISTRATION NUMBERS:NCT02529189 and ISRCTN17373946, Pre-results.
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Project description:Fatigue has been identified in more than one-half of patients with sarcoidosis. Although fatigue is not synonymous with impaired quality of life, most studies of sarcoidosis identify fatigue as a major cause of impaired quality of life.To test the hypothesis that stimulants may have a role in the treatment of fatigued sarcoidosis patients, even without objective evidence of daytime sleepiness.This was a double-blind, placebo-controlled, crossover study of sarcoidosis patients followed up in one sarcoidosis clinic Sarcoidosis patients with fatigue received either armodafinil or placebo with eight weeks of therapy for each arm and a two week washout period before crossover to the other treatment. Initial armodafinil dose was 150mg and increased to 250mg after four weeks. Patients underwent polysomnography and multiple sleep latency testing (MSLT) the following day. Patients with an apnea/hypopnea index <6/hour received either armodafinil or placebo. Polysomnography with MSLT was repeated after each treatment arm.Fifteen patients received the study drug. Fatigue was assessed using the Fatigue Assessment Scale (the lower the score, the less the fatigue) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) (the higher the score, the less the fatigue). After eight weeks of therapy, there was a significant improvement in the Fatigue Assessment Scale during armodafinil treatment (median -4.5, range -20, 5) compared with placebo treatment (median 3.5, range -9, 14, P<0.05) and for the FACIT-F (armodafinil: median 9, range -12, 26 vs. placebo: median -5, range -17, 11, P<0.005). This improvement in fatigue was seen for both those with and without shortened sleep onset latency time during the MSLT.Armodafinil treatment led to a significant reduction in fatigue in sarcoidosis patients. This effect was seen even in patients who did not have excessive daytime somnolence.
| S-EPMC3678278 | biostudies-literature
Project description:Despite the availability of evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them. Tolcapone is a catechol-O-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Conduct a proof of concept study to examine whether a COMT inhibitor would reduce OCD symptoms to a greater extent than placebo. We conducted a randomized, placebo-controlled, double-blind crossover trial in adults with OCD (N = 20). Participants were assessed at baseline, after 2 weeks of tolcapone, and again after 2 weeks of placebo on measures of OCD symptom severity and psychosocial functioning. There was a 1-week washout period between the 2-week treatment phases. Two weeks of tolcapone was associated with significant improvement in OCD versus two weeks of placebo (t = 2.194, P = 0.0409). The mean percentage decreases in the total Yale-Brown obsessive-compulsive scale (YBOCS) scores for the entire sample over the corresponding 2-week period were 16.4% for tolcapone and 3.6% for placebo. These data indicate that brain penetrant COMT inhibitors merit further investigation as a candidate new treatment for OCD.
| S-EPMC7611531 | biostudies-literature
Project description:Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health
2018-04-25 | GSE84453 | GEO
Project description:BACKGROUND:Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to 12%. Previous small studies with onabotulinumtoxin A (OnaA) for RLS have shown inconsistent results. METHODS:Twenty-four patients with an International RLS score (IRLS) of >11 (moderate-severe) were enrolled in this blinded, placebo-controlled crossover study. Twenty-one patients completed the evaluations at 4, 6, and 8 weeks after each injection. One-hundred units of Incobotulinumtoxin A (IncoA) or normal saline were injected into tibialis anterior, gastrocnemius, and biceps femoris muscles each side. RESULTS:Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ?20) score was significant at four weeks (p = 0.0036) and six weeks (p = 0.0325) following IncoA administration compared to placebo. Additionally, there was significant improvement in pain score at six weeks as measured by Visual Analogue Scale (p = 0.04) and the Johns Hopkins Quality of Life Questionnaire (p = 0.01) in the IncoA group. Definite or marked improvement on Patient Global Impression of Change was seen in 7 out of 21 patients in the IncoA group vs. 1 out of 21 patients in the placebo group at 4 weeks (p = 0.012). CONCLUSION:IncoA injection lead to a reduction in severity of RLS symptoms, pain score, and quality of life, without any adverse effects.
| S-EPMC6215171 | biostudies-literature
Project description:BackgroundDysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.MethodClozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.ResultsWhen compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.ConclusionsIn patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
| S-EPMC4954262 | biostudies-literature
Project description:Paraxanthine (PXN) is a metabolite of caffeine that has recently been reported to enhance cognition at a dose of 200 mg. To determine the acute and short-term (7-day) effects of varying doses of PXN on cognitive function and side effects. In a double blind, placebo-controlled, crossover, and counterbalanced manner, 12 healthy male and female volunteers (22.7 ± 4 years, 165 ± 7 cm, 66.5 ± 11 kg, 24.4 ± 3 kg/m2) ingested 200 mg of a placebo (PLA), 50 mg of PXN (ENFINITY™, Ingenious Ingredients, L.P.) + 150 mg PLA, 100 mg PXN + 100 mg PLA, or 200 mg of PXN. With each treatment experiment, participants completed side effect questionnaires and donated a fasting blood sample. Participants then performed a series of tests assessing cognition, executive function, memory, and reaction time. Participants then ingested one capsule of PLA or PXN treatments. Participants then completed side effects and cognitive function tests after 1, 2, 3, 4, 5, and 6 h of treatment ingestion. Participants continued ingesting one dose of the assigned treatment daily for 6-days and returned to the lab on day 7 to donate a fasting blood sample, assess side effects, and perform cognitive function tests. Participants repeated the experiment while ingesting remaining treatments in a counterbalanced manner after at least a 7-day washout period until all treatments were assessed. The Sternberg Task Test (STT) 4-Letter Length Present Reaction Time tended to differ among groups (p = 0.06). Assessment of mean changes from baseline with 95% CI's revealed several significant differences among treatments in Berg-Wisconsin Card Sorting Correct Responses, Preservative Errors (PEBL), and Preservative Errors (PAR Rules). There was also evidence of significant differences among treatments in the Go/No-Go Task tests in Mean Accuracy as well as several time points of increasing complexity among STT variables. Finally, there was evidence from Psychomotor Vigilance Task Test assessment that response time improved over the series of 20 trials assessed as well as during the 6-h experiment in the PXN treatment. Acute and short-term benefits compared to PLA were seen with each dose studied but more consistent effects appeared to be at 100 mg and 200 mg doses. No significant differences were observed among treatments in clinical chemistry panels or the frequency or severity of reported side effects. Results provide evidence that acute ingestion of 100 mg and 200 mg of PXN may affect some measures of cognition, memory, reasoning, and response time as well as help sustain attention. Additionally, that acute and daily ingestion of PXN for 7 days is not associated with any clinically significant side effects. PXN may serve as an effective nootropic agent at doses as low as 50 mg.
| S-EPMC8708375 | biostudies-literature
Project description:BACKGROUND:To assess the efficacy and safety of oral Guanxinshutong (GXST) capsules in Chinese patients with stable angina pectoris (SAP) in a prospective, multicenter, double-Blind, placebo-controlled, randomized clinical trial (clinicaltrials.gov Identifier: NCT02280850). METHODS:Eligible patients were randomized 1:1 to the GXST or placebo group. Current standard antianginal treatment except for nitrate drugs was continued in both groups, who received an additional 4-week treatment of GXST capsule or placebo. Primary endpoint was the change from baseline in angina attack frequency after the 4-week treatment. Secondary endpoints included the reduction of nitroglycerin dose, score of Seatntle Agina Questionnaire, exercise tolerance test defined as time to onset of chest pain and ST-segment depression at least 1?mm greater than the resting one. RESULTS:A total of 300 SAP patients from 12 centers in China were enrolled between January 2013 and October 2015, and they were randomly divided into the GXST group and the placebo group (150 patients in each group). Of whom, 287 patients completed the study (143 patients in the GXST group, 144 patients in the placebo group). The baseline characteristics of the two groups were comparable. After 4-week treatment with GXST capsules, the number of angina attacks and the consumption of short-acting nitrates were significantly reduced. In addition, the quality of life of patients were also substantially improved in the GXST group. No significant differences in the time of onset of angina and 1-mm ST segment depression were noted between the two groups. 7 patients (4.1%) in the GXST group and 3 patients (2.1%) in the placebo group reported at least one adverse event, respectively. CONCLUSIONS:GXST capsules are beneficial for the treatment of SAP patients.
| S-EPMC6907120 | biostudies-literature
Project description:BackgroundGreen tea intake has been shown to improve endurance capacity in animal studies, but whether it has a similar effect on humans remains unclear. A randomized, double-blinded, parallel-controlled study was conducted to evaluate the short-term effect of STA-2, a pharmaceutical preparation of green tea polyphenols, in patients with effort-induced angina and documented positive exercise tolerance test.MethodsA total of 79 patients recruited from three medical centers were randomly assigned to receive 2 STA-2 250 mg capsules, each containing 100 mg green tea polyphenols, three times daily, or placebo for six weeks after two consecutive symptom-limited treadmill exercise tests to ascertain the reproducibility of exercise tolerance.ResultsThere was no difference in total exercise tolerance time from baseline to Week 6 between two groups (p = 0.639). There were also no observed improvements in subgroup analyses stratified by age, gender, and BMI categories. However, a significant reduction in low-density lipoprotein levels was shown in patients in the STA-2 group (-8.99 ± 19.18 mg/dL) versus the placebo group (0.57 ± 19.77 mg/dL), p = 0.037, with greater benefits in patients not taking antihyperlipidemic drugs (STA-2: -9.10 ± 19.96 mg/dL vs. placebo: 4.42 ± 15.08 mg/dL, p = 0.037).ConclusionsSTA-2 treatment for 6 weeks did not increase exercise time as measured on a treadmill. However, this study also indicated that STA-2 treatment could have potential beneficial effects on LDL-cholesterol concentrations.
| S-EPMC4963420 | biostudies-literature