MedPath

Effect of Probiotics on Primary Hypertension

Early Phase 1
Completed
Conditions
Hypertension
Interventions
Biological: Probiotic powder
Biological: Placebo powder
Registration Number
NCT05095350
Lead Sponsor
Chinese Academy of Medical Sciences, Fuwai Hospital
Brief Summary

Gut microbiota was found to play a causal role in the pathogenesis of hypertension. Probiotics were shown to have a potential anti-hypertensive effect in human/rodent studies. This study aims to explore the effect, safety, and underlying mechanisms of the combination of probiotics, containing 10 strains from Lactobacillus and Bifidobacterium, on hypertension, compared with placebo.

Detailed Description

Background: Primary hypertension is the leading risk factor of cardiovascular diseases and all-cause mortality, and contributes to severe global health burden. Emerging evidence has shown a close association between gut microbiota and hypertension. Fecal transplantation from hypertensive patients/animals to germ-free mice caused elevation of blood pressure, indicating a causal role of gut dysbiosis in hypertension. Probiotics were found to have a potential anti-hypertensive effect in both human and rodent studies. Based on the investigators' previous findings of metagenomics analysis of hypertensive, prehypertensive patients and healthy control, hypertensive and prehypertensive patients were lack of probiotics. Therefore, the investigators developed this study to explore the effect, safety, and underlying mechanisms of the combination of probiotics, containing 10 strains from Lactobacillus and Bifidobacterium, on hypertension, compared with placebo.

Objective: To explore the effect, safety, and underlying mechanisms of the combination of probiotics on grade 1 primary hypertension and prehypertension.

Study Design: A multicenter, randomized, double-blinded, placebo-controlled pilot study.

Data quality control and statistical analysis: The investigators have invited professional statistic analysts to assist in analyzing data and a third party to supervise data quality.

Ethics: The Ethics Committee of Fuwai Hospital approved this study. Informed consent before patient enrollment is required.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
115
Inclusion Criteria
  1. Age 18~60 years.
  2. Grade 1 hypertension and part of prehypertension (initial diagnosis or free from antihypertensive drugs within 2 weeks): 130 mmHg ≤ Average office SBP < 160 mmHg, and/or 85 mmHg ≤ Average office DBP < 100 mmHg, according to the "2018 Chinese Guidelines for Prevention and Treatment of Hypertension" and "National guideline for hypertension management in China (2019)".
  3. Patients with informed consent after thorough explanation.
Exclusion Criteria
  1. Antibiotics or probiotics usage within the last 2 weeks.
  2. Participants of other clinical trials currently or within last 3 months.
  3. Antihypertensive medications usage currently or within last 2 weeks.
  4. Diagnosed secondary hypertension
  5. History of diabetes mellitus.
  6. History of peripheral atherosclerosis.
  7. Severe hepatic or renal diseases (ALT >3 times the upper limit of normal value, or end-stage renal disease on dialysis or eGFR <30 mL/min/1.73 m2, or serum creatinine >2.5 mg/dl [>221 μmol/L]).
  8. History of stroke (not including lacunar infarction and transient ischemic attack [TIA]).
  9. History of coronary heart disease.
  10. Sustained atrial fibrillation or arrhythmias at recruitment disturbing the electronic BP measurement.
  11. NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months.
  12. Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period.
  13. Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease.
  14. Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome.
  15. Cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent.
  16. Participants preparing for or under pregnancy and/or lactation.
  17. With special diet habits, such as vegetarians.
  18. Active gastritis or enteritis; gastrointestinal ulcers or bleeding; post-gastrointestinal surgery, such as intestinal excision.
  19. Other conditions inappropriate for recruitment according to the investigators.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Probiotic powderProbiotic powderThe probiotic powder contains 10 strains from Lactobacillus and Bifidobacterium genus. Participants will orally take two sachets daily and last for 8 weeks.
Placebo powderPlacebo powderThe placebo powder consists of maltodextrin and contains no probiotics. Participants will orally take two sachets daily and last for 8 weeks.
Primary Outcome Measures
NameTimeMethod
Change in Office Systolic Blood Pressure (SBP)From baseline to day 56

Change in Office Systolic Blood Pressure (SBP)

Secondary Outcome Measures
NameTimeMethod
Change in Body Mass IndexBaseline, Day 56

Change in Body Mass Index

Change in daytime average DBP via 24-hour Ambulatory BP MonitoringBaseline, Day28, Day 56, Day 84

Change in daytime average DBP via 24-hour Ambulatory BP Monitoring

Change in daytime average SBP via 24-hour Ambulatory BP MonitoringBaseline, Day28, Day 56, Day 84

Change in daytime average SBP via 24-hour Ambulatory BP Monitoring

Change in Office Diastolic Blood Pressure (DBP)Baseline, Day28, Day 56, Day 84

Change in Office Diastolic Blood Pressure (DBP)

Change in average DBP via 24-hour Ambulatory BP MonitoringBaseline, Day28, Day 56, Day 84

Change in average DBP via 24-hour Ambulatory BP Monitoring

Number of Participants with Adverse Events (AEs) as a Measure of SafetyBaseline, Day28, Day 56, Day 84

Number of Participants with Adverse Events (AEs) as a Measure of Safety

Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic AnalysisBaseline, Day28, Day 56, Day 84

Intestinal microbiota composition is obtained through sequencing of DNAs from feces samples and bioinformatic analysis. Changes in the intestinal microbiota composition before and after intervention (probiotics or placebo) is defined as a secondary outcome. This is stratified by: 1. Randomization (probiotics or placebo); 2. Changes in office SBP.

Change in nightime average DBP via 24-hour Ambulatory BP MonitoringBaseline, Day28, Day 56, Day 84

Change in nightime average DBP via 24-hour Ambulatory BP Monitoring

Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic AnalysisBaseline, Day28, Day 56, Day 84

Metabolomics analysis is a quantitative analysis of all metabolites in the sample. Metabolites in serum are detected using liquid or gas chromatography combined with mass spectrometry, and the composition and abundance of each metabolite are obtained. Changes in the serum metabolite composition before and after intervention (probiotics or placebo) is defined as a secondary outcome. This is stratified by: 1. Randomization (probiotics or placebo); 2. Changes in office SBP.

Randomisation Change in Office SBP

Change in Blood Uric AcidBaseline, Day 56

Change in Blood Uric Acid

Change in Office SBPBaseline, Day28, Day 56, Day 84

Change in Office SBP

Change in average SBP via 24-hour Ambulatory BP MonitoringBaseline, Day28, Day 56, Day 84

Change in average SBP via 24-hour Ambulatory BP Monitoring

Change in nightime average SBP via 24-hour Ambulatory BP MonitoringBaseline, Day28, Day 56, Day 84

Change in nightime average SBP via 24-hour Ambulatory BP Monitoring

Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic AnalysisBaseline, Day28, Day 56, Day 84

Intestinal microbiota function is obtained through sequencing of DNAs from feces samples and bioinformatic analysis according to functions related to detected genes. Changes in the intestinal microbiota function before and after intervention (probiotics or placebo) is defined as a secondary outcome. This is stratified by: 1. Randomization (probiotics or placebo); 2. Changes in office SBP.

Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic AnalysisBaseline, Day28, Day 56, Day 84

Metabolomics analysis is a quantitative analysis of all metabolites in the sample. Metabolites in feces are detected using liquid or gas chromatography combined with mass spectrometry, and the composition and abundance of each metabolite are obtained. Changes in the intestinal metabolite composition before and after intervention (probiotics or placebo) is defined as a secondary outcome. This is stratified by: 1. Randomization (probiotics or placebo); 2. Changes in office SBP.

Randomisation Change in Office SBP

Change in Fasting Blood Glucose LevelBaseline, Day 56

Change in Fasting Blood Glucose Level

Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)Baseline, Day 56

Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)

Trial Locations

Locations (6)

Fu Wai Hospital, Chinese Academy of Medical Sciences

🇨🇳

Beijing, Beijing, China

Longgang District People's Hospital of Shenzhen

🇨🇳

Shenzhen, Guangdong, China

Renmin Hospital of Wuhan University

🇨🇳

Wuhan, Hubei, China

The Second Affiliated Hospital of Baotou Medical Collage

🇨🇳

Baotou, Neimenggu, China

Renji Hospital, Shanghai Jiaotong University School of Medicine

🇨🇳

Shanghai, Shanghai, China

Sichuan Provincial People's Hospital

🇨🇳

Chengdu, Sichuan, China

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