Anja Mähler1,2,3,4, Nicola Wilck5,6,7,8,9, Geraldine Rauch6,10, Ralf Dechend5,11,6,7,8,12, Dominik N Müller5,11,6,7,8. 1. Experimental and Clinical Research Center, a cooperation between Charité - Universitätsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Berlin, Germany. anja.maehler@charite.de. 2. Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. anja.maehler@charite.de. 3. Berlin Institute of Health, Berlin, Germany. anja.maehler@charite.de. 4. DZHK (German Centre for Cardiovascular Research) partner site Berlin, Berlin, Germany. anja.maehler@charite.de. 5. Experimental and Clinical Research Center, a cooperation between Charité - Universitätsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Berlin, Germany. 6. Berlin Institute of Health, Berlin, Germany. 7. DZHK (German Centre for Cardiovascular Research) partner site Berlin, Berlin, Germany. 8. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. 9. Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin Charité - Universitätsmedizin Berlin, Berlin, Germany. 10. Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 11. Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 12. Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany.
Abstract
BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular disease and leads to target organ damage including stroke, heart failure, and kidney disease. About 1.5 billion people worldwide have hypertension, and it is estimated that it causes about 8 million deaths each year. Although there are several drugs available to lower blood pressure (BP), a great proportion of treated patients does not reach recommended treatment targets. Typical antihypertensive drugs target the vessels, the kidneys, and the heart. However, our gut microbiota also influences cardiovascular health, and gut dysbiosis is associated with hypertension. In this study protocol, we investigate the potential BP-lowering effect of a probiotic in patients with grade 1 hypertension. METHODS: This study is an exploratory, randomized, double-blind, placebo-controlled, parallel-group study. One hundred ten patients with grade 1 hypertension (treated or untreated) will be randomized to either the probiotic Vivomixx® or placebo. The primary endpoint is the nocturnal systolic BP measured by ambulatory blood pressure monitoring after 8 weeks adjusted for the baseline value. The secondary endpoints are changes from baseline in nocturnal diastolic BP, antihypertensive medication, fecal microbiome composition, fecal and serum metabolome, immune cell phenotypes, glucose variability after three standardized breakfasts, and health-related quality of life (PROMIS-29). We also assess the safety profile of the intervention. DISCUSSION: We postulate that various administrated bacteria (Lactobacilli, Bifidobacteria, and Streptococcus thermophilus) convert dietary components into active metabolites that positively affect immune cell function. A reduction of pro-inflammatory immune cell function could promote a BP-lowering effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT03906578 . Registered on 08 April 2019.
RCT Entities:
BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular disease and leads to target organ damage including stroke, heart failure, and kidney disease. About 1.5 billion people worldwide have hypertension, and it is estimated that it causes about 8 million deaths each year. Although there are several drugs available to lower blood pressure (BP), a great proportion of treated patients does not reach recommended treatment targets. Typical antihypertensive drugs target the vessels, the kidneys, and the heart. However, our gut microbiota also influences cardiovascular health, and gut dysbiosis is associated with hypertension. In this study protocol, we investigate the potential BP-lowering effect of a probiotic in patients with grade 1 hypertension. METHODS: This study is an exploratory, randomized, double-blind, placebo-controlled, parallel-group study. One hundred ten patients with grade 1 hypertension (treated or untreated) will be randomized to either the probiotic Vivomixx® or placebo. The primary endpoint is the nocturnal systolic BP measured by ambulatory blood pressure monitoring after 8 weeks adjusted for the baseline value. The secondary endpoints are changes from baseline in nocturnal diastolic BP, antihypertensive medication, fecal microbiome composition, fecal and serum metabolome, immune cell phenotypes, glucose variability after three standardized breakfasts, and health-related quality of life (PROMIS-29). We also assess the safety profile of the intervention. DISCUSSION: We postulate that various administrated bacteria (Lactobacilli, Bifidobacteria, and Streptococcus thermophilus) convert dietary components into active metabolites that positively affect immune cell function. A reduction of pro-inflammatory immune cell function could promote a BP-lowering effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT03906578 . Registered on 08 April 2019.
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