Clinical trial NCT05095350: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hypertension
Keywords: Hypertension
Microbiome
Probiotics
Treatment
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Municipal Education Commission
First posted: 2021-10-27
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Office Systolic Blood Pressure (SBP)
timeFrame: From baseline to day 56
Secondary outcomes:
measure: Change in Office SBP
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in Office Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in daytime average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in daytime average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in nightime average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in nightime average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Changes in Intestinal Microbiota Function Pre- and Post-intervention via Metagenomic Analysis
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Changes in Intestinal Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Changes in Serum Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
timeFrame: Baseline, Day28, Day 56, Day 84
measure: Change in Fasting Blood Glucose Level
timeFrame: Baseline, Day 56
measure: Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)
timeFrame: Baseline, Day 56
measure: Change in Blood Uric Acid
timeFrame: Baseline, Day 56
measure: Change in Body Mass Index
timeFrame: Baseline, Day 56
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fu Wai Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Shenzhen
country: China
facility: Longgang District People's Hospital of Shenzhen
state: Guangdong
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Baotou
country: China
facility: The Second Affiliated Hospital of Baotou Medical Collage
state: Neimenggu
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: JUN CAI
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.