Prevention of Cognitive Decline Clinical Trial
— NAPSOfficial title:
Nattokinase Atherothrombotic Prevention Study
| NCT number | NCT02080520 |
| Other study ID # | SDF-01 |
| Secondary ID | |
| Status | Completed |
| Phase | N/A |
| First received | |
| Last updated | |
| Start date | April 2014 |
| Est. completion date | July 31, 2019 |
| Verified date | March 2024 |
| Source | University of Southern California |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 265 |
| Est. completion date | July 31, 2019 |
| Est. primary completion date | July 31, 2019 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 55 Years to 100 Years |
| Eligibility | Inclusion Criteria: - Age >55 years - Male or postmenopausal female (no uterine bleeding for >6 months) Exclusion Criteria: - 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Atherosclerosis Research Unit, University of Southern California | Los Angeles | California |
| Lead Sponsor | Collaborator |
|---|---|
| University of Southern California |
United States,
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 Hemorhe — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | Change in Neurocognitive Function (Global Cognition) | All neuropsychological test scores at baseline and follow-up assessments were standardized ([raw score - mean score]/standard deviation) using the baseline means and standard deviations from the entire NAPS sample. Each of three cognitive composite scores was calculated at baseline (composite score of 0 equals performance at the mean of each test at baseline) and follow-up assessments as the weighted average of the individual donor standardized test scores, weighted by the inverse correlation among tests. The change from baseline (endpoint minus baseline cognitive outcome) was computed for each of the cognitive composite scores (verbal memory, global cognition, and executive functions). Since the outcome is not a single test but a weighted average of multiple tests, the range is not standard and not reported and there is no clinically relevant threshold. A composite score and change in composite score greater than 0 represent better cognitive performance. | Baseline and 36 months |