Back to resultsEffect of Probiotics on Primary Hypertension
Primary Purpose
Hypertension
Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Probiotic powder
Placebo powder
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring Hypertension, Microbiome, Probiotics, Treatment
Eligibility Criteria
Inclusion Criteria:
- Age 18~60 years.
- 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)".
- Patients with informed consent after thorough explanation.
Exclusion Criteria:
- Antibiotics or probiotics usage within the last 2 weeks.
- Participants of other clinical trials currently or within last 3 months.
- Antihypertensive medications usage currently or within last 2 weeks.
- Diagnosed secondary hypertension
- History of diabetes mellitus.
- History of peripheral atherosclerosis.
- 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]).
- History of stroke (not including lacunar infarction and transient ischemic attack [TIA]).
- History of coronary heart disease.
- Sustained atrial fibrillation or arrhythmias at recruitment disturbing the electronic BP measurement.
- NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months.
- Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period.
- Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease.
- Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome.
- Cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent.
- Participants preparing for or under pregnancy and/or lactation.
- With special diet habits, such as vegetarians.
- Active gastritis or enteritis; gastrointestinal ulcers or bleeding; post-gastrointestinal surgery, such as intestinal excision.
- Other conditions inappropriate for recruitment according to the investigators.
Sites / Locations
- Fu Wai Hospital, Chinese Academy of Medical Sciences
- The First Affiliated Hospital, Sun Yat-sen University
- Longgang District People's Hospital of ShenzhenRecruiting
- Renmin Hospital of Wuhan UniversityRecruiting
- The Second Affiliated Hospital of Baotou Medical Collage
- Renji Hospital, Shanghai Jiaotong University School of MedicineRecruiting
- Sichuan Provincial People's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Probiotic powder
Placebo powder
Arm Description
The probiotic powder contains 10 strains from Lactobacillus and Bifidobacterium genus. Participants will orally take two sachets daily and last for 8 weeks.
The placebo powder consists of maltodextrin and contains no probiotics. Participants will orally take two sachets daily and last for 8 weeks.
Outcomes
Primary Outcome Measures
Change in Office Systolic Blood Pressure (SBP)
Change in Office Systolic Blood Pressure (SBP)
Secondary Outcome Measures
Change in Office SBP
Change in Office SBP
Change in Office Diastolic Blood Pressure (DBP)
Change in Office Diastolic Blood Pressure (DBP)
Change in average SBP via 24-hour Ambulatory BP Monitoring
Change in average SBP via 24-hour Ambulatory BP Monitoring
Change in average DBP via 24-hour Ambulatory BP Monitoring
Change in average DBP via 24-hour Ambulatory BP Monitoring
Change in daytime average SBP via 24-hour Ambulatory BP Monitoring
Change in daytime average SBP via 24-hour Ambulatory BP Monitoring
Change in daytime average DBP via 24-hour Ambulatory BP Monitoring
Change in daytime average DBP via 24-hour Ambulatory BP Monitoring
Change in nightime average SBP via 24-hour Ambulatory BP Monitoring
Change in nightime average SBP via 24-hour Ambulatory BP Monitoring
Change in nightime average DBP via 24-hour Ambulatory BP Monitoring
Change in nightime average DBP via 24-hour Ambulatory BP Monitoring
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
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.
Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis
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 Analysis
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
Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
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 Fasting Blood Glucose Level
Change in Fasting Blood Glucose Level
Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
Change in Blood Uric Acid
Change in Blood Uric Acid
Change in Body Mass Index
Change in Body Mass Index
Full Information
NCT ID
NCT05095350
First Posted
October 4, 2021
Last Updated
December 30, 2021
Sponsor
Chinese Academy of Medical Sciences, Fuwai Hospital
Collaborators
Beijing Municipal Education Commission
1. Study Identification
Unique Protocol Identification Number
NCT05095350
Brief Title
Effect of Probiotics on Primary Hypertension
Official Title
Effect of Probiotics on Grade 1 Primary Hypertension and Prehypertension and the Underlying Mechanism: a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 5, 2021 (Actual)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences, Fuwai Hospital
Collaborators
Beijing Municipal Education Commission
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Hypertension, Microbiome, Probiotics, Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Probiotic powder
Arm Type
Experimental
Arm Description
The probiotic powder contains 10 strains from Lactobacillus and Bifidobacterium genus. Participants will orally take two sachets daily and last for 8 weeks.
Arm Title
Placebo powder
Arm Type
Placebo Comparator
Arm Description
The placebo powder consists of maltodextrin and contains no probiotics. Participants will orally take two sachets daily and last for 8 weeks.
Intervention Type
Biological
Intervention Name(s)
Probiotic powder
Intervention Description
Probiotic powder containing 10 strains from Lactobacillus and Bifidobacterium genus.
Intervention Type
Biological
Intervention Name(s)
Placebo powder
Intervention Description
Placebo powder containing maltodextrin and no probiotics.
Primary Outcome Measure Information:
Title
Change in Office Systolic Blood Pressure (SBP)
Description
Change in Office Systolic Blood Pressure (SBP)
Time Frame
From baseline to day 56
Secondary Outcome Measure Information:
Title
Change in Office SBP
Description
Change in Office SBP
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in Office Diastolic Blood Pressure (DBP)
Description
Change in Office Diastolic Blood Pressure (DBP)
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in average SBP via 24-hour Ambulatory BP Monitoring
Description
Change in average SBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in average DBP via 24-hour Ambulatory BP Monitoring
Description
Change in average DBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in daytime average SBP via 24-hour Ambulatory BP Monitoring
Description
Change in daytime average SBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in daytime average DBP via 24-hour Ambulatory BP Monitoring
Description
Change in daytime average DBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in nightime average SBP via 24-hour Ambulatory BP Monitoring
Description
Change in nightime average SBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in nightime average DBP via 24-hour Ambulatory BP Monitoring
Description
Change in nightime average DBP via 24-hour Ambulatory BP Monitoring
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Description
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
Description
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.
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis
Description
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.
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
Description
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
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
Description
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
Time Frame
Baseline, Day28, Day 56, Day 84
Title
Change in Fasting Blood Glucose Level
Description
Change in Fasting Blood Glucose Level
Time Frame
Baseline, Day 56
Title
Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
Description
Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
Time Frame
Baseline, Day 56
Title
Change in Blood Uric Acid
Description
Change in Blood Uric Acid
Time Frame
Baseline, Day 56
Title
Change in Body Mass Index
Description
Change in Body Mass Index
Time Frame
Baseline, Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18~60 years.
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)".
Patients with informed consent after thorough explanation.
Exclusion Criteria:
Antibiotics or probiotics usage within the last 2 weeks.
Participants of other clinical trials currently or within last 3 months.
Antihypertensive medications usage currently or within last 2 weeks.
Diagnosed secondary hypertension
History of diabetes mellitus.
History of peripheral atherosclerosis.
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]).
History of stroke (not including lacunar infarction and transient ischemic attack [TIA]).
History of coronary heart disease.
Sustained atrial fibrillation or arrhythmias at recruitment disturbing the electronic BP measurement.
NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months.
Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period.
Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease.
Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome.
Cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent.
Participants preparing for or under pregnancy and/or lactation.
With special diet habits, such as vegetarians.
Active gastritis or enteritis; gastrointestinal ulcers or bleeding; post-gastrointestinal surgery, such as intestinal excision.
Other conditions inappropriate for recruitment according to the investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
QIANHUI LING
Phone
01088392165
Email
lingqh@outlook.com
First Name & Middle Initial & Last Name or Official Title & Degree
YAN ZHANG
Phone
01088392165
Email
Dr_zhangyan@whu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
JUN CAI
Organizational Affiliation
Chinese Academy of Medical Sciences, Fuwai Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fu Wai Hospital, Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100037
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
JUN CAI
Facility Name
The First Affiliated Hospital, Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Tao
Facility Name
Longgang District People's Hospital of Shenzhen
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruijuan Han
Facility Name
Renmin Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mingwei Bao
Facility Name
The Second Affiliated Hospital of Baotou Medical Collage
City
Baotou
State/Province
Neimenggu
ZIP/Postal Code
014000
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Renji Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meng Jiang
Facility Name
Sichuan Provincial People's Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Shu
12. IPD Sharing Statement
Citations:
PubMed Identifier
28143587
Citation
Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017 Feb 1;5(1):14. doi: 10.1186/s40168-016-0222-x.
Results Reference
background
PubMed Identifier
29143823
Citation
Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mahler A, Balogh A, Marko L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Fratzer C, Krannich A, Gollasch M, Grohme DA, Corte-Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Muller DN. Salt-responsive gut commensal modulates TH17 axis and disease. Nature. 2017 Nov 30;551(7682):585-589. doi: 10.1038/nature24628. Epub 2017 Nov 15.
Results Reference
background
PubMed Identifier
31953983
Citation
Robles-Vera I, Toral M, de la Visitacion N, Sanchez M, Gomez-Guzman M, Romero M, Yang T, Izquierdo-Garcia JL, Jimenez R, Ruiz-Cabello J, Guerra-Hernandez E, Raizada MK, Perez-Vizcaino F, Duarte J. Probiotics Prevent Dysbiosis and the Rise in Blood Pressure in Genetic Hypertension: Role of Short-Chain Fatty Acids. Mol Nutr Food Res. 2020 Mar;64(6):e1900616. doi: 10.1002/mnfr.201900616. Epub 2020 Feb 6.
Results Reference
background
PubMed Identifier
25047574
Citation
Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension. 2014 Oct;64(4):897-903. doi: 10.1161/HYPERTENSIONAHA.114.03469. Epub 2014 Jul 21.
Results Reference
background
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Effect of Probiotics on Primary Hypertension
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