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The primary objective of this study is to investigate if a Bifidobacterium-based probiotic intervention would reduce clinic systolic BP in untreated middle-aged Chinese men and women with hypertension according to ACC/AHA guidelines (SBP ≥130 mm Hg) after 12 weeks of treatment. The investigators anticipate that this feasibility study will provide rationale to conduct a larger randomized clinical trial and preliminary data to estimate the power/ sample size of a larger RCT.
The primary objective of this study is to investigate if a Bifidobacterium-based probiotic intervention would reduce clinic systolic BP in untreated middle-aged Chinese men and women with hypertension according to ACC/AHA guidelines (SBP ≥130 mm Hg) after 12 weeks of treatment. The investigators anticipate that this feasibility study will provide rationale to conduct a larger randomized clinical trial and preliminary data to estimate the power/ sample size of a larger RCT.
The four independent but interrelated objectives of this study include:
Additionally, the investigators will conduct sex-stratified analysis to explore potential sex differences in BP lowering response to the intervention since sex-linked differences in the initiation and progression of hypertension pathology are well-established, and the investigators recently reported that association between GM and hypertension is also sex-linked.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 30 recruited participants receiving commercially available probiotics supplements | Experimental | 30 community-dwelling, middle-aged Hong Kong Chinese (15 men and 15 women) with hypertension according to ACC/AHA guidelines (SBP ≥130 mm Hg) who are not taking antihypertensive agents and are free of symptomatic cardiovascular or cerebrovascular diseases will be recruited in this study. Participants will be recruited via our outreach promotion program or social media and recruitment posters will be distributed physically or posted online. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bifidobacterium probiotics supplementation | Biological | The 12-week research period consists of one prescreening and baseline visit (week -1) and three follow-up visits (week 4 (±7days), week 8 (±7days) and week 12 (±7days)). The participants will be instructed to fast overnight before their visits in the mornings of week -1 and week 12. The measurements will include documentation of personal and demographic information; three consecutive clinic BP readings; 24-hour ambulatory BP monitoring; a 3-day diet diary to monitor consistency of dietary intake; collection of fecal samples and blood samples for analysis of GM composition and biomarkers, respectively at baseline, and week 8 and 12. Only participants who are able to provide all the required data and samples within 7 days after the prescreening and baseline visit (week -1) will be eligible to receive the Bifidobacterium supplementation with 20 billion cfu once a day for 12 weeks. They will be instructed to mix the probiotics with water and consume with their dinner. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean seated clinic systolic blood pressure (SBP) | Three consecutive BP measurements will be assessed using an automatic BP monitor, Microlife BP A200 AFIB (Microlife, Taiwan). Prior to taking BP measurements, participants will be instructed to sit and rest for at least five minutes. Participants will be advised to maintain an upright posture, with their arms positioned at heart level and palms facing upwards. Additionally, they will be advised to refrain from speaking during process. The average of three BP measurements will be taken to minimize random error. | During clinical visits at: - Baseline (a week prior to treatment), - Week 4, 8 of treatment - Week 12 of treatment (end of treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean seated clinic diastolic blood pressure (DBP) | Three consecutive BP measurements will be assessed using an automatic BP monitor, Microlife BP A200 AFIB (Microlife, Taiwan). Prior to taking BP measurements, participants will be instructed to sit and rest for at least five minutes. Participants will be advised to maintain an upright posture, with their arms positioned at heart level and palms facing upwards. Additionally, they will be advised to refrain from speaking during process. The average of three BP measurements will be taken to minimize random error. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gary Kui-Kai Lau | Contact | +852 22554249 | gkklau@hku.hk |
| Name | Affiliation | Role |
|---|---|---|
| Gary KK Lau | The University of Hong Kong | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Hong Kong | Hong Kong | Hong Kong |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26690980 | Background | Chumpitazi BP, Self MM, Czyzewski DI, Cejka S, Swank PR, Shulman RJ. Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations. Neurogastroenterol Motil. 2016 Mar;28(3):443-8. doi: 10.1111/nmo.12738. Epub 2015 Dec 21. | |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| During clinical visits at: - Baseline (a week prior to treatment), - Week 4, 8 of treatment - Week 12 of treatment (end of treatment) |
| Mean 24-hour ambulatory SBP | A calibrated ambulatory BP monitoring device, TM-2441 (A&D Medical, Japan) will be fitted onto the participants, with the BP cuff placed on their non-dominant arm to record the 24-hour ambulatory BP. The BP will be measured every 30 minutes from 6 am to 10 pm and then every 60 minutes from 10 pm to 6 am. | During clinical visits at: - Baseline (a week prior to treatment), - Week 12 of treatment (end of treatment) |
| Gut microbiome composition and functions | Stool GM sequencing will be performed to compare GM abundance before and after probiotics intervention. This will enable metagenomic assembly community profiling and functional profiling, while facilitating the identification of presented taxa, their abundance, biochemical potential, and other relevant information. Other GM species that may be associated with hypertension could also be identified and provide valuable insights for the development of future GM-based intervention strategies. A set of OMNIgene-OMR205 kits (DNA Genotek, Canada) will be utilized for the collection and stabilization of gut microbial DNA and RNA, facilitating the profiling of gut microbiomes. We will also inquire about the participants' bowel habit concurrently, utilizing the Bristol Stool Chart as reference. | During clinical visits at: - Baseline (a week prior to treatment), - Week 12 of treatment (end of treatment) |
| Plasma levels of gut microbiome-derived metabolites, short-chain fatty acids (SCFA) and gamma amino butyric acids (GABA) | The level of SCFAs in blood sample will be detected by a two-steps analysis: the blood sample will be first derivatized by 1-propanol/pyridine (3:2, v: v) and propyl chloroformate followed by the quantification using 7890B gas chromatography-mass spectrometry after centrifugation of blood. | During clinical visits at: - Baseline (a week prior to treatment), - Week 12 of treatment (end of treatment) |
| Serum levels of proinflammatory and oxidative stress markers | Various inflammatory markers, including IL-1, IL-6, IL-8, TNF-α, IL-10 will be assessed using LEGENDplex™ 13-plex pro-inflammatory cytokine panel (BioLegend Inc., USA). Damages caused by radicals or excessive oxidants will be measured in the blood. DNA/RNA damage will be assessed by 8-Hydroxygaunaosine (8-OHG) or detecting the general DNA damage via comet assay. Lipid damage will be assessed by measuring malondialdehyde (MDA) levels and protein modification will be assessed by measuring the levels of advanced glycation end products (AGE). A portion of every blood sample will also be collected and preserved in a PAXgene Blood RNA tube manufactured by QIAGEN in Germany. This tube enables the extraction and purification of intracellular RNA for subsequent molecular diagnostic testing. | During clinical visits at: - Baseline (a week prior to treatment), - Week 12 of treatment (end of treatment) |
| Sex differences in BP reduction after the intervention | Demographics to be collected during baseline visit. |
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