scholarly journals Microbial Interventions to Control And Reduce Blood Pressure In Australia (Microbia): Rationale And Design of A Double-Blinded Randomised Cross-Over Placebo Controlled Trial

2021 ◽  
Author(s):  
Dakota Rhys-Jones ◽  
Rachel Climie ◽  
Hamdi Jama ◽  
Paul Gill ◽  
Geoffrey Head ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Gut Microbiota ◽  
Resistant Starch ◽  
Corn Starch ◽  
Controlled Trial ◽  
Short Chain Fatty Acids ◽  
Reduce Blood Pressure ◽  
Clinical Trial Registry ◽  
Double Blinded

Abstract Background: Hypertension is a prevalent chronic disease worldwide that remains poorly controlled. Recent studies support the concept that the gut microbiota is involved in the development of hypertension, and that dietary fibre intake may act through the gut microbiota to lower blood pressure (BP). Resistant starch is a type of prebiotic fibre which is metabolized by commensal bacteria in the colon to produce short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. Previous work in pre-clinical models provide strong evidence that both prebiotic fibre as well as SCFAs (i.e. postbiotics) can prevent the development of hypertension. The aim of this clinical trial is to determine if acetylated and butyrylated modified resistant starch can decrease BP of hypertensive individuals via the modulation of the gut microbiota and release of high levels of SCFAs. Methods: This is a phase IIa double-blinded, randomised, cross-over, placebo controlled trial. Participants are randomly allocated to receive either a diet containing 40g/day of the modified resistant starch or placebo (corn starch or regular flour) for three weeks on each diet, with a three week washout period between the two diets. BP is measured in the office, at home, and using a 24 hour ambulatory device. Arterial stiffness is measured using carotid-to-femoral pulse wave velocity. Our primary endpoint is a reduction in ambulatory daytime systolic BP. Secondary endpoints include changes to circulating cytokines, immune markers, and modulation to the gut microbiome. Discussion: The findings of this study will provide the first evidence for the use of a combination of pre- and postbiotics to lower BP in humans. The results are expected at the end of 2021.Trial registration: Australia and New Zealand Clinical Trial Registry ACTRN12619000916145, registered on 1/07/2019.

scholarly journals Microbial Interventions to Control and Reduce Blood Pressure in Australia (MICRoBIA): rationale and design of a double-blinded randomised cross-over placebo controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dakota Rhys-Jones ◽  
Rachel E. Climie ◽  
Paul A. Gill ◽  
Hamdi A. Jama ◽  
Geoffrey A. Head ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Gut Microbiota ◽  
Resistant Starch ◽  
Corn Starch ◽  
Controlled Trial ◽  
Short Chain Fatty Acids ◽  
Trial Registration ◽  
Clinical Trial Registry ◽  
Double Blinded

Abstract Background Hypertension is a prevalent chronic disease worldwide that remains poorly controlled. Recent studies support the concept that the gut microbiota is involved in the development of hypertension and that dietary fibre intake may act through the gut microbiota to lower blood pressure (BP). Resistant starch is a type of prebiotic fibre which is metabolised by commensal bacteria in the colon to produce short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Previous work in pre-clinical models provides strong evidence that both prebiotic fibre as well as SCFAs (i.e. postbiotics) can prevent the development of hypertension. The aim of this clinical trial is to determine if acetylated and butyrylated modified resistant starch can decrease BP of hypertensive individuals via the modulation of the gut microbiota and release of high levels of SCFAs. Methods This is a phase IIa double-blinded, randomised, cross-over, placebo controlled trial. Participants are randomly allocated to receive either a diet containing 40 g/day of the modified resistant starch or placebo (corn starch or regular flour) for 3 weeks on each diet, with a 3-week washout period between the two diets. BP is measured in the office, at home, and using a 24-h ambulatory device. Arterial stiffness is measured using carotid-to-femoral pulse wave velocity. Our primary endpoint is a reduction in ambulatory daytime systolic BP. Secondary endpoints include changes to circulating cytokines, immune markers, and modulation to the gut microbiome. Discussion The findings of this study will provide the first evidence for the use of a combination of pre- and postbiotics to lower BP in humans. The results are expected at the end of 2021. Trial registration Australia and New Zealand Clinical Trial Registry ACTRN12619000916145. Registered on 1 July 2019.

scholarly journals Polyphenol-rich juices reduce blood pressure measures in a randomised controlled trial in high normal and hypertensive volunteers

2015 ◽  
Vol 114 (7) ◽  
pp. 1054-1063 ◽  
Author(s):  
Torunn Elisabeth Tjelle ◽  
Linda Holtung ◽  
Siv Kjølsrud Bøhn ◽  
Kjersti Aaby ◽  
Magne Thoresen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Placebo Group ◽  
Controlled Trial ◽  
Reduce Blood Pressure ◽  
Lower Blood ◽  
Normotensive Subjects ◽  
Randomised Controlled ◽  
Double Blinded ◽  
Stage 1 ◽  
Group 1

Intake of fruits and berries may lower blood pressure (BP), most probably due to the high content of polyphenols. In the present study, we tested whether consumption of two polyphenol-rich juices could lower BP. In a randomised, double-blinded, placebo-controlled trial of 12 weeks, 134 healthy individuals, aged 50–70 years, with high normal range BP (130/85–139/89 mmHg, seventy-two subjects) or stage 1-2 hypertension (140/90–179/109 mmHg, sixty-two subjects), were included. They consumed 500 ml/d of one of either (1) a commercially available polyphenol-rich juice based on red grapes, cherries, chokeberries and bilberries; (2) a juice similar to (1) but enriched with polyphenol-rich extracts from blackcurrant press-residue or (3) a placebo juice (polyphenol contents 245·5, 305·2 and 76 mg/100 g, respectively). Resting BP was measured three times, with a 1 min interval, at baseline and after 6 and 12 weeks of intervention. Systolic BP significantly reduced over time (6 and 12 weeks, respectively) in the pooled juice group compared with the placebo group in the first of the three measurements, both for the whole study group (6·9 and 3·4 mmHg; P= 0·01) and even more pronounced in the hypertensive subjects when analysed separately (7·3 and 6·8 mmHg; P= 0·04). The variation in the BP measurements was significantly reduced in the pooled juice group compared with the placebo group (1·4 and 1·7 mmHg; P= 0·03). In conclusion, the present findings suggest that polyphenol-rich berry juice may contribute to a BP- and BP variability lowering effect, being more pronounced in hypertensive than in normotensive subjects.

scholarly journals A double blinded placebo controlled comparative clinical trial to evaluate the effectiveness of Siddha medicines, Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy treatment in the management of symptomatic COVID 19 patients - a structured summary of a study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anurag Srivastava ◽  
Manickavasagam Rengaraju ◽  
Saurabh Srivastava ◽  
Vimal Narayan ◽  
Vivek Gupta ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
List Type ◽  
Rt Pcr ◽  
Randomized Controlled ◽  
End Of Treatment ◽  
Stay Time ◽  
Full Protocol ◽  
Double Blinded

Abstract Objectives The primary objectives of the study are to determine the effectiveness of the Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy Treatment to compared with Placebo (Decaffeinated Tea) with standard Allopathy Treatment in the management of Symptomatic COVID 19 patients and also in reduction of Hospital Stay Time & Changes in Immunological (IL6) and Bio Chemical Markers (Ferritin, CRP, D-Dimer and LDH). The secondary objectives are to evaluate the safety of the trial medicines and their effects in the reduce the risks of the disease. In addition, to document the profile of Symptomatic COVID 19 patients as per Siddha Principles. Trial Design A Double Blinded, Three arm, Single Centre, Placebo Controlled, Exploratory and comparative Randomized Controlled Trial Participants Patients who were admitted to the COVID Care Centre at Govt. Institute of Medical Sciences. Noida in India will be recruited. These will be patients with Mild and Moderate symptoms with laboratory confirmed COVID 19 (RT – PCR Tested Positive) aged 18-65, willing and consenting to participate. Intervention and comparator Arm I: Decaffeinated Tea (Placebo – similar in taste and appearance to the other Two Decoctions), 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm II: Nilavembu Kudineer (The Siddha Medicines which is used as a standard Anti-Viral drug for the past Pandemics by Siddha Physicians) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm III: Kaba Sura Kudineer (The Siddha Medicine which is proposed to be used as a Treatment for COVID 19 based on Siddha Literature) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. The investigational drugs are registered products under the Govt.of India and bought from GMP Certified Manufacturing Units. Main Outcomes Primary outcomes: Reduction in Viral load of SARS-CoV-2 at the end of treatment (10 days). 2. Time taken to convert Patient from symptomatic to Asymptomatic based on Reduction in clinical symptoms (10 days). 3. Effect of drugs inflammatory markers (IL6,) at the end of treatment (10 days). 4. Reduction in hospital stay time (20 days follow up). (Based on RT PCR CT Value 3rd, 6th if needed 10th day). (Based on IL 6 Value needed 10th day or IL6 value on turning negative. (entry level/exit level). Secondary outcomes (10 days): Reduction in use of Intensive Supportive Care. 2. Reduction in incidence of complications (Acute Respiratory Distress Syndrome, other systemic complications). 3. MuLBSTA score for viral pneumonia (multinodular infiltration, hypo-lymphocytosis, bacterial co infection, Total Leucocyte Count (TLC ≤ 0.8 x 109/L), smoking history, hyper-tension and age) score. 4. Laboratory markers (Haematological & Biochemical Markers). 5. Adverse events/effects Siddha-based measurements. 6. Siddha Udaliyal assessment by using Yakkai Ilakkanam (YI) Tool to diagnose body condition for covid-19 patients. Randomisation The assignment of the participants into 3 Groups will be allocated in 1:1:1 Ratio through randomization Blocks in Microsoft Excel by a Statistician who is not involved in the study. The allocation scheme will be made by another statistician by using a closed envelope after the assessment of eligibility and Informed consent procedures. The groups will be balanced for age and sex with 3:1 Ratio in each group for mild: severe COVID-19 symptoms. Blinding The Study is Double Blinded. Participants and Investigators were blinded. Numbers to be randomized (Sample size) Sample size could not be calculated, Since there are no prior trials on KSK and NVK as a comparative trial. In addition, there are no prior trials on KSK and NVK in this region. A total Number of 120 Patients, 40 each in 3 groups will be recruited in 1:1:1 Ratio. Trial Status Protocol Number : SCRUND GIMS Noida Study 1,Version: 2.0 Protocol Date : 20.08.2020 The recruitment period is completed for the trial. The Trial started its recruitment on 22.8.2020. We anticipate study including data analysis will finish in January 2021. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. Trial Registration The trial protocol was registered with CTRI (Clinical Trial Registry of India) and number is CTRI/2020/08/027286 on 21.08.2020 Full Protocol The full Protocol is attached as an additional file, Accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar 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 SPIRIT guidelines.

scholarly journals Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander V. Lebedev ◽  
Jonna Nilsson ◽  
Joanna Lindström ◽  
William Fredborg ◽  
Ulrika Akenine ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cognitive Training ◽  
Cognitive Aging ◽  
Latent Variables ◽  
Fluid Intelligence ◽  
Controlled Trial ◽  
Basic Research ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Healthy Elderly

AbstractCognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effects are small. Basic research has implicated dopaminergic signalling in plasticity. We investigated whether supplementation with the dopamine-precursor L-dopa improves effects of cognitive training on performance. Sixty-three participants for this randomised, parallel-group, double-blind, placebo-controlled trial were recruited via newspaper advertisements. Inclusion criteria were: age of 65–75 years, Mini-Mental State Examination score >25, absence of serious medical conditions. Eligible subjects were randomly allocated to either receive 100/25 mg L-dopa/benserazide (n = 32) or placebo (n = 31) prior to each of twenty cognitive training sessions administered during a four-week period. Participants and staff were blinded to group assignment. Primary outcomes were latent variables of spatial and verbal fluid intelligence. Compared to the placebo group, subjects receiving L-dopa improved less in spatial intelligence (−0.267 SDs; 95%CI [−0.498, −0.036]; p = 0.024). Change in verbal intelligence did not significantly differ between the groups (−0.081 SDs, 95%CI [−0.242, 0.080]; p = 0.323). Subjects receiving L-dopa also progressed slower through the training and the groups displayed differential volumetric changes in the midbrain. No statistically significant differences were found for the secondary cognitive outcomes. Adverse events occurred for 10 (31%) and 7 (23%) participants in the active and control groups, correspondingly. The results speak against early pharmacological interventions in older healthy adults to improve broader cognitive functions by targeting the dopaminergic system and provide no support for learning-enhancing properties of L-dopa supplements in the healthy elderly. The findings warrant closer investigation about the cognitive effects of early dopamine-replacement therapy in neurological disorders. This trial was preregistered at the European Clinical Trial Registry, EudraCT#2016-000891-54 (2016-10-05).

scholarly journals Naoxuekang, Xinnaoshutong and Xuesaitong capsules for treating stroke: a protocol for a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e015983 ◽  
Author(s):  
Huiling Chen ◽  
Hongbo Cao ◽  
Xu Guo ◽  
Meidan Zhao ◽  
Qing Xia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Facial Paralysis ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Initial Treatment Period ◽  
Double Blind Clinical Trial ◽  
Registration Number ◽  
Index Value ◽  
Randomised Controlled

IntroductionAfter stroke, hemiplegia, dysphasia and facial paralysis can manifest during the convalescent period. Currently, no Chinese patent medicine (CPM) is previously reported to cure each of these symptoms primarily, and thus, there are no relevant instructions for the use of CPM. This study presents a new approach based on comparative effectiveness research to distinguish the curative effects of three CPMs that are often used in stroke convalescence to determine the ideal medicine for the treatment of each symptom.Methods and analysisIn this multicentre and double-blind clinical trial, stratified randomisation is used to group the patients according to their primary symptoms (hemiplegia, dysphasia and facial paralysis). Three strata will be enrolled, with 80 eligible participants included in each stratum. Each stratum will be randomly and equally divided into four groups, and each group will receive one of the following treatments: Naoxuekang, Xinnaoshutong (XNST), Xuesaitong (XST) or placebo. This study will include two stages: the initial treatment period (30 days) and a follow-up period (180 days). Three replicates for each data point will be completed during this trial. The first visit will occur on day 0 after enrolment, the second visit on day 30±2 and the third visit on day 210±5. The Delphi technique is adopted to achieve index weighting, which ensures that the evaluation outcome is patient oriented. The weighted index value will be computed as the final measurement index of the outcome.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of Tianjin University of Traditional Chinese Medicine (registration number TJUTCM-EC20160007). The results will be offered for publication in peer-reviewed journals.Trial registration numberThis trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17010397). The date of registration was 11 January 2017.

scholarly journals Guidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension

Hypertension ◽  
2019 ◽  
Vol 74 (6) ◽  
pp. 1279-1293 ◽  
Author(s):  
Francine Z. Marques ◽  
Hamdi A. Jama ◽  
Kirill Tsyganov ◽  
Paul A. Gill ◽  
Dakota Rhys-Jones ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Environmental Factors ◽  
Gut Microbiota ◽  
Environmental History ◽  
Gut Microbiome ◽  
Blood Pressure Measurement ◽  
Short Chain Fatty Acids ◽  
Experimental Models ◽  
Human Studies ◽  
Experimental Hypertension

Hypertension is a complex and modifiable condition in which environmental factors contribute to both onset and progression. Recent evidence has accumulated for roles of diet and the gut microbiome as environmental factors in blood pressure regulation. However, this is complex because gut microbiomes are a unique feature of each individual reflecting that individual’s developmental and environmental history creating caveats for both experimental models and human studies. Here, we describe guidelines for conducting gut microbiome studies in experimental and clinical hypertension. We provide a complete guide for authors on proper design, analyses, and reporting of gut microbiota/microbiome and metabolite studies and checklists that can be used by reviewers and editors to support robust reporting and interpretation. We discuss factors that modulate the gut microbiota in animal (eg, cohort, controls, diet, developmental age, housing, sex, and models used) and human studies (eg, blood pressure measurement and medication, body mass index, demographic characteristics including age, cultural identification, living structure, sex and socioeconomic environment, and exclusion criteria). We also provide best practice advice on sampling, storage of fecal/cecal samples, DNA extraction, sequencing methods (including metagenomics and 16S rRNA), and computational analyses. Finally, we discuss the measurement of short-chain fatty acids, metabolites produced by the gut microbiota, and interpretation of data. These guidelines should support better transparency, reproducibility, and translation of findings in the field of gut microbiota/microbiome in hypertension and cardiovascular disease.

Effectiveness of acarbose in treating elderly patients with diabetes with postprandial hypotension

2017 ◽  
Vol 65 (4) ◽  
pp. 772-783 ◽  
Author(s):  
Jie Zhang ◽  
Lixin Guo
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Elderly Patients ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Postprandial Hypotension ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Patients With Diabetes ◽  
Group B

Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels.Trial registration numberChinese Clinical Trial Registry ChiCTR-IPR-15006177.

scholarly journals Modifications of Gut Microbiota after Grape Pomace Supplementation in Subjects at Cardiometabolic Risk: A Randomized Cross-Over Controlled Clinical Trial

Foods ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1279
Author(s):  
Sara Ramos-Romero ◽  
Daniel Martínez-Maqueda ◽  
Mercè Hereu ◽  
Susana Amézqueta ◽  
Josep Lluís Torres ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gut Microbiota ◽  
Cardiometabolic Risk ◽  
Short Chain Fatty Acids ◽  
Grape Pomace ◽  
Controlled Clinical Trial ◽  
Insulin Levels ◽  
Equivalent Control ◽  
Cardiometabolic Markers ◽  
Dietary Bioactive Compounds

Polyphenols are dietary bioactive compounds able to induce modifications in the gut microbiota profile, although more clinical studies are needed. With this aim, a randomized cross-over clinical trial was conducted, where 49 subjects at cardiometabolic risk (exhibiting at least two metabolic syndrome factors) were supplemented with a daily dose of 8 g of grape pomace (GP) for 6 weeks, with an equivalent control (CTL) period. The levels of total bacteria and Bacteroidetes, Firmicutes, Lactobacilliales, Bacteroides and Prevotella were estimated in fecal DNA by quantitative real-time PCR (qPCR), while fecal short-chain fatty acids (SCFAs) were assessed by gas chromatography. Several cardiometabolic markers were evaluated in blood samples. GP reduced insulin levels only in half of the participants (responders). GP supplementation did not cause significant modifications in the microbiota profile of the whole group, except for a tendency (p = 0.059) towards a decrease in the proportion of Lactobacilliales, while it increased the proportion of Bacteroides in non-responder subjects. The reduction of insulin levels in subjects at cardiometabolic risk upon GP supplementation appears not to be induced by changes in the major subgroups of gut microbiota. Further studies at the species level may help to elucidate the possible role of microbiota in GP-induced insulinemic status.

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