Effect of Intensive FMT on Primary Hypertension

Hypertension Clinical Trial

Official title:

Effect and Safety of Intensive Fecal Microbiota Transplantation on Primary Hypertension: a Randomized Clinical Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05608447
• Other study ID #: 2017-GZ10 (Part III)
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 1, 2023
• Est. completion date: September 30, 2023

Study information

• Verified date: November 2022
• Source: Chinese Academy of Medical Sciences, Fuwai Hospital
• Contact: Jun Jun, MD,PhD
• Phone: 86-010-88392165
• Email: caijun7879[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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was observed after short-course FMT intervention but recovery after intervention termination(Trials. 2022;23(1):178, unpublished results).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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 72
• Est. completion date: September 30, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Biological:
• FMT capsules
FMT capsules containing extensively screened donor stool.

Other:
• Placebo capsules
Placebo capsules that do not contain donor stool or any active drug.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Shantou University	Shantou	Guangdong
China	Shanxi Bethune Hospital	Taiyuan	Shanxi
China	The People's Hospital of Ji Xian District	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences, Fuwai Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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, Högenauer 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. — View 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-contro — View 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. do — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Office Systolic Blood Pressure (SBP)	Change in Office Systolic Blood Pressure (SBP)	From baseline to Week 8
Secondary	Change in Office Systolic Blood Pressure (SBP)	Change in Office Systolic Blood Pressure (SBP)	Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 12
Secondary	Change in Office Diastolic Blood Pressure (DBP)	Change in Office Diastolic Blood Pressure (DBP)	Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12
Secondary	Change in Home Systolic Blood Pressure (SBP)	Change in Home Systolic Blood Pressure (SBP)	Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12
Secondary	Change in Home Diastolic Blood Pressure (DBP)	Change in Home Diastolic Blood Pressure (DBP), compared with baseline	Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 12
Secondary	Change in average SBP via 24-hour Ambulatory BP Monitoring	Change in average SBP via 24-hour Ambulatory BP Monitoring	Baseline, Week 4, Week 8, Week 12
Secondary	Change in average DBP via 24-hour Ambulatory BP Monitoring	Change in average DBP via 24-hour Ambulatory BP Monitoring	Baseline, Week 4, Week 8, Week 12
Secondary	Change in daytime SBP via 24-hour Ambulatory BP Monitoring	Change in daytime SBP via 24-hour Ambulatory BP Monitoring	Baseline, Week 4, Week 8, Week 12
Secondary	Change in daytime DBP via 24-hour Ambulatory BP Monitoring	Change in daytime DBP via 24-hour Ambulatory BP Monitoring	Baseline, Week 4, Week 8, Week 12
Secondary	Change in nighttime SBP via 24-hour Ambulatory BP Monitoring	Change in nighttime SBP via 24-hour Ambulatory BP Monitoring	Baseline, Week 4, Week 8, Week 12
Secondary	Change in nighttime DBP via 24-hour Ambulatory BP Monitoring	Change in nighttime DBP via 24-hour Ambulatory BP Monitoring	Baseline, Week 4, Week 8, Week 12
Secondary	Number of Participants with Adverse Events (AEs) as a Measure of Safety	Number of Participants with Adverse Events (AEs) as a Measure of Safety	All AEs over 12 weeks
Secondary	Changes in Intestinal Microbiota Composition Pre- and Post-intervention via Metagenomic Analysis	Changes in Intestinal Microbiota Composition Pre- and Post-intervention (FMT or Placebo) via Metagenomic Analysis, stratified by: Randomisation; Change in Office SBP	Baseline, Week 4, Week 8, Week 12
Secondary	Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis	Changes in Intestinal Microbiota function revealed by KEGG pathways and KEGG Orthology (KO) Pre- and Post-intervention via Metagenomic Analysis, stratified by: Randomisation; Change in Office SBP	Baseline, Week 4, Week 8, Week 12
Secondary	Durability of Engraftment of Donor Microbiome Following FMT	Durability of engraftment of donor microbiome following FMT, measured by similarity comparison of intestinal microbiota composition between donor and recipient	Baseline, Week 4, Week 8, Week 12
Secondary	Changes in Plasma Metabolite Composition Pre- and Post-intervention via Metabolomic Analysis	Changes in Plasma Metabolite Composition Pre- and Post-intervention (FMT or Placebo) via Metabolomic Analysis, stratified by: Randomisation; Change in Office SBP	Baseline, Week 4, Week 8, Week 12
Secondary	Change in Fasting Blood Glucose Level	Change in Fasting Blood Glucose Level	Baseline, Week 4, Week 8, Week 12
Secondary	Change in blood HbA1c level	Change in blood glycosylated hemoglobin, type A1C (HbA1c) level	Baseline, Week 4, Week 8, Week 12
Secondary	Change in blood lipid level	Change in Blood Lipid Level (Total Cholesterol, Total Triglyceride, Low Density Lipoprotein Cholesterol, High Density Lipoprotein Cholesterol)	Baseline, Week 4, Week 8, Week 12
Secondary	Change in Body Mass Index	Change in Body Mass Index	Baseline, Week 4, Week 8, Week 12