Clinical trial NCT05608447: Effect of Intensive FMT on Primary Hypertension
Official title: Effect and Safety of Intensive Fecal Microbiota Transplantation on Primary Hypertension: a Randomized Clinical Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hypertension
Keywords: hypertension
microbiome
fecal microbiota transplantation
treatment
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
First posted: 2022-11-08
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mounting preclinical and clinical evidences have proved the causal role of gut microbiota on the pathogenesis of primary hypertension. Restoration of gut microbiota ameliorated high BP in rodents and/or human cases.A hypothesis is thus raised that gut microbiome restoration can be a potential approach to ameliorate hypertension. This study will perform intense fecal microbiota transplantation (FMT) intervention via oral capsules, in comparison with placebo capsules, to investigate the effect, safety and underlying mechanisms of gut microbiome intervention on primary hypertension.

Detailed description: Primary hypertension is a most prevalent cardiovascular diseases, and becomes a severe global public health issue because of the high morbidity and potential risk to other cardiovascular diseases. Several animal studies and diverse patient cohorts reported that the disorder of gut microbiome correlated with hypertension. Based on the investigators' previous work findings, a casual role of gut microbiome disorder was observed in primary hypertension (Microbiome. 2017;5(1):14.), and trend of ameliorating SBP was observed after short-course FMT intervention but recovery after intervention termination(Trials. 2022;23(1):178, unpublished results). The investigators therefore developed a consecutive study of intensive FMT intervention on primary hypertension.

Objective: To explore the effect, safety and underlying mechanisms of intensive FMT on primary hypertension.

Study Design: A multi-center, randomized, blinded, placebo-controlled pilot study.

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

Eligibility criteria: Inclusion Criteria:

1. Age 18\~65 years.
2. Established Diagnosis of Grade 1 Hypertension (initial diagnosis or free from antihypertensive drugs within a month): 140mmHg≤ Office SBP\<160mmHg and/or 90mmHg≤ Office DBP\<100mmHg for three measurements at different days without any antihypertensive medications, according to the"2010 Chinese Guidelines for Prevention and Treatment of Hypertension".
3. Patients with informed consent after thorough explanation.

Exclusion Criteria:

1. Antibiotics or probiotics usage within last 4 weeks
2. Participants of other clinical trials related to hypertension currently or within last 3 months
3. Antihypertensive medications usage currently or within last month
4. Diagnosed secondary hypertension
5. 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 \[\>221 μmol/L\])
6. History of large atherosclerotic cerebral infarction or hemorrhagic stroke(not including lacunar infarction and transient ischemic attack \[TIA\])
7. Hospitalization for myocardial infarction within last 6 months; Coronary revascularization (PCI or CABG) within last 12 months; Planned for PCI or CABG in the next 12 months.
8. Sustained atrial fibrillation or arrhythmias at recruitment disturbing the electronic BP measurement.
9. NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months.
10. Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period.
11. Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease.
12. Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome.
13. Cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent.
14. Participants preparing for or under pregnancy and/or lactation.
15. Other conditions inappropriate for recruitment according to the investigators.

Primary outcomes:
measure: Change in Office Systolic Blood Pressure (SBP)
timeFrame: From baseline to Week 8
Secondary outcomes:
measure: Change in Office Systolic Blood Pressure (SBP)
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 12
measure: Change in Office Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12
measure: Change in Home Systolic Blood Pressure (SBP)
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12
measure: Change in Home Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12
measure: Change in average SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in average DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in daytime SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in daytime DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in nighttime SBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in nighttime DBP via 24-hour Ambulatory BP Monitoring
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety
timeFrame: All AEs over 12 weeks
measure: Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Durability of Engraftment of Donor Microbiome Following FMT
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Changes in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in Fasting Blood Glucose Level
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in blood HbA1c level
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in blood lipid level
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Change in Body Mass Index
timeFrame: Baseline, Week 4, Week 8, Week 12
Other outcomes:
Locations:
city: Shantou
country: China
facility: The Second Affiliated Hospital of Shantou University
state: Guangdong
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Tianjin
country: China
facility: The People's Hospital of Ji Xian District
state: Tianjin
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Jun Cai, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Hogenauer C, Malfertheiner P, Mattila E, Milosavljevic T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A; European FMT Working Group. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017 Apr;66(4):569-580. doi: 10.1136/gutjnl-2016-313017. Epub 2017 Jan 13.
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: Fan L, Ren J, Chen Y, Wang Y, Guo Z, Bu P, Yang J, Ma W, Zhu B, Zhao Y, Cai J. Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study. Trials. 2022 Feb 24;23(1):178. doi: 10.1186/s13063-022-06086-2.