Nattokinase Atherothrombotic Prevention Study

NCT02080520 | Completed Results DMC

• 1 other identifier: SDF-01
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

Brief Summary

The potential for nattokinase to "thin" blood and to reduce blood clotting by positive antithrombotic and fibrinolytic effects presents a unique opportunity to safely study such effects on cardiovascular disease and cognition. Unfortunately, such studies of antithrombotic and fibrinolytic pathways of prevention have been limited due to lack of safe compounds and the adverse reactions associated with current agents such as Coumadin. Nattokinase, an over-the-counter supplement used for cardiovascular health, is the most active functional constituent of natto, a fermented soy product. Natto has been consumed primarily by the Japanese for over 1000 years, a population with one of the lowest risks for cardiovascular disease and dementia. Cardiovascular disease and dementia remain the most challenging age-related health risks of the 21st century for Americans necessitating development of further effective preemptive strategies. Whether reducing the propensity for thrombus formation and/or increasing fibrinolytic activity can prevent the progression of atherosclerosis and cognitive decline has not yet been determined. Using nattokinase under primary prevention conditions, the investigators propose to conduct a randomized, double-blinded, placebo-controlled trial to determine whether decreasing atherothrombotic risk can reduce the progression of subclinical atherosclerosis and cognitive decline. The investigators propose to randomize 240 healthy non-demented women and men to nattokinase supplementation or to placebo for three years. The primary trial endpoints will be measurement of carotid arterial wall thickness and arterial stiffness, early changes of atherosclerosis that can be measured safely by non-invasive imaging techniques. The secondary trial endpoint will be ascertained through change in cognition measured by a neuropsychological battery. In addition, biochemical blood measurements and in vitro studies will be conducted to compare the effects of nattokinase relative to placebo on blood coagulation and thrombus break-down capabilities, blood flow properties, inflammation and inflammatory activation of endothelial cells that line blood vessels.

Conditions

Prevention of Subclinical Atherosclerosis Progression; Prevention of Cognitive Decline

Keywords

Arterial compliance; Arterial distensibility; Atherosclerosis; Atherothrombosis; Blood pressure; Cardiovascular disease (CVD); Carotid artery; Carotid artery intima-media thickness (CIMT); Coagulation; Cognition; Fermented soy; Fibrinolysis; Natto; Nattokinase; Prevention; Randomized controlled trial; Rheology; Soy; Soybeans; Thrombosis

Outcome Measures

Primary Outcomes (3)

• Progression of Subclinical Atherosclerosis

  Rate of change in distal common carotid artery (CCA) far wall intima-media thickness (mm per year) in computer image processed B-mode ultrasonograms will be a co-primary trial endpoint.

  Baseline x 2 and then every 6 months, up to 3 years

• Progression of Carotid Artery Stiffness (Distensibility)

  Rate of change in arterial distensibility of the distal common carotid artery (CCA) determined from lumen diameters at systole and diastole and systolic and diastolic blood pressure. CCA lumen diameters will be determined from computer image processed B-mode ultrasonograms. This is a co-primary trial endpoint.

  Baseline x 2 and then every 6 months, up to 3 years

• Carotid Artery Stiffness Progression (Compliance)

  Rate of change in arterial compliance of the distal common carotid artery (CCA) determined from lumen diameters at systole and diastole and systolic and diastolic blood pressure. CCA lumen diameters will be determined from computer image processed B-mode ultrasonograms. This is a co-primary trial endpoint.

  Baseline x 2 and then every 6 months, up to 3 years

Secondary Outcomes (1)

• Change in Neurocognitive Function (Global Cognition)

  Baseline and 36 months

Study Arms (2)

Nattokinase

ACTIVE COMPARATOR

Oral nattokinase 2,000 fibrinolytic units daily

Dietary Supplement: Nattokinase

Placebo

PLACEBO COMPARATOR

Matched placebo daily

Other: Placebo

Interventions

Nattokinase DIETARY_SUPPLEMENT

Nattokinase

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 55 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>55 years
• Male or postmenopausal female (no uterine bleeding for \>6 months)

You may not qualify if:

• Clinical signs, symptoms, or personal history of cardiovascular disease
• Diabetes mellitus or fasting serum glucose \>140 mg/dL
• Plasma triglyceride levels \>500 mg/dL
• Uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>110 mmHg)
• Uncontrolled tachycardia or irregular heart rates (i.e., atrial fibrillation)
• Thyroid disease (untreated)
• Renal insufficiency (defined as serum creatinine \>2.0 mg/dL)
• Life threatening illness with prognosis \<5 years
• Current use of lipid-lowering medication
• Current use of food supplements containing soy, soy protein, isoflavones or other phytoestrogens
• Known sensitivity or allergy to soy or nuts
• Regular aspirin or other antiplatelet medication use
• Use of anticoagulants
• Bleeding diatheses or tendencies

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

Atherosclerosis Research Unit, University of Southern California

Los Angeles, California, 90033, United States

Location

Related Publications (1)

• Hodis HN, Mack WJ, Meiselman HJ, Kalra V, Liebman H, Hwang-Levine J, Dustin L, Kono N, Mert M, Wenby RB, Huesca E, Rochanda L, Li Y, Yan M, St John JA, Whitfield L. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353. doi: 10.3233/CH-211147.

  PMID: 33843667 RESULT

MeSH Terms

Conditions

Atherosclerosis; Thrombosis; Cardiovascular Diseases

Interventions

nattokinase

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Embolism and Thrombosis

Results Point of Contact

• Title: Howard N. Hodis, M.D.
• Organization: Atherosclerosis Research Unit, University of Southern California

athero@usc.edu

323-442-1478

Study Officials

• Howard N. Hodis, M.D.

  Atherosclerosis Research Unit, University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Harry J Bauer and Dorothy Bauer Rawlins Professor of Cardiology, Professor of Medicine, Population and Public Health Sciences, and Molecular Pharmacology and Toxicology, Director, Atherosclerosis Research Unit

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: March 6, 2014
• Study Start: April 1, 2014
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: March 19, 2024
• Results First Posted: March 19, 2024

Record last verified: 2024-03

Locations

US (1)