Effects of Nattokinase on Cardiovascular Risk, Gut Microbiota, Sleep, and Cognition in Metabolic Syndrome With Sleep Disorders.

Effects of Nattokinase on Cardiovascular Disease Risk Factors, Gut Microbiota, Sleeping and Cognitive Function in Patients With Risk of Metabolic Syndrome Along With Sleeping Disorder.

Nattokinase has been confirmed by many experiments to have a thrombolytic effect, but there are currently very few studies on nattokinase's effect on gut microbiota, sleeping status, and age-related cognitive function. Therefore, this study intends to explore the effect of nattokinase on cardiovascular disease risk factors, intestinal microbiota, sleep status and cognitive function in patients with metabolic syndrome risk and sleep disorders. This study will be a double-blind, self-control, placebo, crossover trial, and recruit 70-80 participants over 18 years old, and have risk of metabolic syndrome and sleep disorders. They will be divided into a placebo group and an experimental group. The experimental period was divided into two phases (12 weeks for each) and a 2-week washout period. In the first phase, 2 placebo or nattokinase capsules were given each day (each capsule contained nattokinase 3000FU, 2 capsules per day). After 12 weeks, a 2-week washout period was entered, and the second phase was entered for a crossover trial. At the 0th and 12th weeks of each stage, body position, blood pressure, blood biochemical values, sleep quality questionnaire, and cognitive function questionnaire will be measured, and feces will be collected for bacterial analysis. In addition, to improve the compliance of the trial, it is planned to ask the subjects to return for a follow-up visit in the 6th week of each phase, and to measure the subject's body composition and blood pressure. This study expects that daily supplementation of 2 nattokinase capsules for 12 weeks can improve cardiovascular risk factors, sleep quality and cognitive function, while also maintaining healthy intestinal flora.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Syndrome; Sleeping Disorders
• Intervention / Treatment: Dietary supplement: Nattokinase; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Suh-Ching Yang; Phone Number: +886-2-2736-1661 Ext. 6553; Email: sokei@tmu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 110
    • Recruiting
    • Taipei Medical University
    • Contact: Suh-Ching Yang; Phone Number: +886-2-2736-1661 Ext. 6553; Email: sokei@tmu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Over 18 years old

2. Meet the criteria of MetS: meet at least two of the following four items will be recognized as at risk of metabolic syndrome:

   1. Abdominal obesity: Male≧90cm (35 inches); Female≧80cm (31inches)
   2. High blood pressure: Systolic blood pressure≧120mmHg or diastolic blood pressure≧80mmHg
   3. High fasting blood glucose: Fasting blood glucose≧100mg/dL
   4. Dyslipidemia: High fasting triglycerides (≧150mg/dL) or low high-density lipoprotein cholesterol (HDL-C) (<40mg/dL for male, <50mg/dL for female)
3. The Apnea Hypopnea Index (AHI) was diagnosed by overnight multi-channel sleep physiology examination (Polysomnography, PSG) or Home Sleep Apnea Test (HSAT) to be between 5 and 30, indicating mild or moderate sleep apnea.
4. No major mental illness or obvious symptoms of anxiety or depression
5. No combination with other primary sleep diseases

Exclusion Criteria:

1. Body mass index (BMI) >30 kg/m^2
2. Chronic diseases: abnormal liver and kidney function, abnormal gastrointestinal function, cardiovascular disease, high blood pressure, diabetes mellitus, and hyperlipidemia, etc.
3. Participants requiring medication for conditions not specified in exclusion criterion (2), who are unable to maintain a stable treatment regimen throughout the trial
4. Malignant tumors
5. Pregnancy or breastfeeding
6. Person expected to perform the surgery.
7. Those who have participated in other clinical trials in the past 28 days.
8. May be allergic to the ingredients in the test materials, or take drugs or dietary supplements that may affect the test results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: nattokinase; Dietary supplement: nattokinase (containing nattokinase 3000FU per capsule) This group will be given supplements for 12 weeks.	Dietary supplement: Nattokinase; Participants will be divided into a placebo group and an experimental group. The experimental period was divided into two phases (12 weeks for each) and a 2-week washout period. In the first phase, 2 nattokinase capsules were given each day (each capsule contained nattokinase 3000FU, 2 capsules per day). After 12 weeks, a 2-week washout period was entered, and the second phase was entered for a crossover trial.
Placebo Comparator: Placebo Comparator: placebo; Placebo treatment (identical capsules containing Microcrystalline Cellulose)	Other: Placebo; Participants will be divided into a placebo group and an experimental group. The experimental period was divided into two phases (12 weeks for each) and a 2-week washout period. In the first phase, 2 placebo capsules were given each day (each capsule contained Microcrystalline Cellulose, 2 capsules per day). After 12 weeks, a 2-week washout period was entered, and the second phase was entered for a crossover trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline The Pittsburgh Sleep Quality Index (PSQI) at 3 months	PSQI is used to evaluate sleeping quality. A self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval.	At 0th week, and 12th week for each of the two phases.
Change from Baseline Insomnia Severity Scale at 3 months	ISI is a simple self-assessment questionnaire for evaluating the severity of insomnia, assessing the severity of insomnia over the past two weeks in the study participants.	At 0th week, and 12th week for each of the two phases.
Change from Baseline Epworth Sleepiness Scale (ESS) at 3 months	ESS is a self-administered questionnaire, and is used to assess the "daytime sleepiness" of the patients.	At 0th week, and 12th week for each of the two phases.
Change from Baseline Patient Health Questionnaire at 3 months	PHQ-9 is a widely used tool for assessing depressive symptoms in both clinical and research settings, evaluating the severity of depressive symptoms over the past two weeks through 9 questions.	At 0th week, and 12th week for each of the two phases.
Change from Baseline Generalized Anxiety Disorder at 3 months	GAD-7 is a brief self-report scale specifically designed to assess the frequency and severity of anxiety symptoms over the past two weeks.	At 0th week, and 12th week for each of the two phases.
Change from Baseline Oguri-Shirakawa-Azumi Sleep Inventory MA version at 3 months	OSA Sleep Inventory MA version is a psychological measurement tool suitable for clinical settings and for middle-aged and elderly individuals who are unable to appropriately respond to multiple-choice questions, used to assess an individual's self-evaluation of sleep upon waking.	At 0th week, and 12th week for each of the two phases.
Change from Baseline The Cambridge Neuropsychological Test Automated Battery at 3 months	CANTAB (Cambridge Neuropsychological Test Automated Battery) is a computerized cognitive function testing system developed by the University of Cambridge, This study will use the preclinical dementia test battery recommended by CANTAB. This test battery has been proven to have better sensitivity and discriminative ability compared to traditional assessment methods including ADAS-cog and MMSE, and can detect cognitive function changes in the short to medium term. The overall assessment includes the following 7 subtests: Motor Screening Task (MOT); Reaction Time (RTI); Paired Associates Learning (PAL); Spatial Working Memory (SWM); Pattern Recognition Memory (PRM); Delayed Matching to Sample (DMS); Rapid Visual Information Processing (RVP)	At 0th week, and 12th week for each of the two phases.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometric Assessment	body weight (kg)	At 0th week, 6th week, and 12th week for each of the two phases.
Anthropometric Assessment	Body fat mass (%/kg)	At 0th week, 6th week, and 12th week for each of the two phases.
Anthropometric Assessment	Skeletal muscle mass (%/kg)	At 0th week, 6th week, and 12th week for each of the two phases.
Blood pressure	blood pressure (mmHg)	At 0th week, 6th week, and 12th week for each of the two phases.
Liver Function	Serum AST (U/L)	At 0th week, and 12th week for each of the two phases.
Liver Function	Serum ALT (U/L)	At 0th week, and 12th week for each of the two phases.
Kidney Function	Serum BUN (mg/dL)	At 0th week, and 12th week for each of the two phases.
Kidney Function	Creatinine (mg/dL)	At 0th week, and 12th week for each of the two phases.
Kidney Function	eGFR (mL/min)	At 0th week, and 12th week for each of the two phases.
Kidney Function	uric acid (mg/dL)	At 0th week, and 12th week for each of the two phases.
Lipid Profile	Serum HDL-C (mg/dL)	At 0th week, and 12th week for each of the two phases.
Lipid Profile	Serum LDL-C (mg/dL)	At 0th week, and 12th week for each of the two phases.
Lipid Profile	Serum triglyceride (mg/dL)	At 0th week, and 12th week for each of the two phases.
Lipid Profile	Serum total cholesterol (mg/dL)	At 0th week, and 12th week for each of the two phases.
Hematology	Complete Blood Count	At 0th week, and 12th week for each of the two phases.
Antioxidative Status	Concentration of thiobarbituric acid-reactive substance	At 0th week, and 12th week for each of the two phases.
Antioxidative Status	Glutathione/oxidized glutathione ratio.	At 0th week, and 12th week for each of the two phases.
Fecal Microbiota	Using 16S rRNA and next-generation sequencing to analyze gut microbiota composition.	At 0th week, and 12th week for each of the two phases.

Collaborators and Investigators

• Sponsor: Taipei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2025
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): February 11, 2027

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Metabolic Diseases; Glucose Metabolism Disorders; Sleep Wake Disorders; Insulin Resistance; Hyperinsulinism; Nutritional and Metabolic Diseases; Parasomnias; Metabolic Syndrome; nattokinase
• Other Study ID Numbers: N202412072

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No