Clinical trial NCT01766180: Cerebrovascular and Cognitive Improvement by Resveratrol (resVida) and Fruitflow-II (CCIRF-II)
Official title: Association Between Fruitflow-II Treatment (Alone or in Combination With Resveratrol) and Changes in Cerebral Blood Flow, Fitness and Cognitive Function in Adults With Memory Complaints
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Memory Impairment
Keywords: Memory
Fruitflow
Resveratrol (resVida)
Cerebral blood flow
Cardiopulmonary exercise test
Maximal VO2
Lead sponsor: Neurolgy Institute for Brain Health and Fitness
Sponsor class: OTHER
Collaborators: name: DSM Nutritional Products, Inc.
First posted: 2013-01-11
Enrollment: 80
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Fruitflow-II, Resveratrol (resVida), alone or in combination, are effective in the treatment of memory problems in adult patients with memory impairment. We also evaluate effects of these medications on blood flow to the brain and fitness, to find whether the possible improvement in memory is associated with the alterations in these parameters.

Detailed description: Accumulating evidence suggests that tomato consumption has cardiovascular benefits, primarily through increasing blood flow in vivo; the active ingredient in tomato, or its extract (Fruitflow) have been shown to inhibit glycoprotein IIb/IIIa, similar to aspirin (which has antiplatelet activity and is used for secondary prevention of cardiovascular and cerebrovascular events in patients). Considering the fact that Fruitflow can improve the platelet function and peripheral blood flow, we hypothesized that Fruitflow can also increase the blood flow in the brain and thereby possibly enhance memory and cognitive function in middle-aged or elderly people who have memory complaints. Therefore, the initial goal of our study is to evaluate the effects of Fruitflow on brain blood and cardiovascular function by using Transcranial Doppler ultrasound (to check for changes in cerebral blood flow), cardiovascular fitness testing (to check for changes in VO2-max and stroke volume), and neurocognitive evaluation (to check for changes in memory and executive function).

Many pathways such as inflammation and oxidative stress are involved in the pathophysiology of memory loss with ageing. Recent studies have shown that a natural compound found in the skin of red grapes and also in wine, called "Resveratrol", have beneficial effects for prevention of cognitive decline by reducing inflammation and improving cardiovascular function. Therefore, our next goal is to evaluate whether administration of Resveratrol, by itself or in combination with Fruitflow, can improve brain blood flow, VO2-max, and cognitive performance.

Thus our clinical trial will have the following 4 arms: Fruitflow, Resveratrol, Fruitflow/Resveratrol combination, and placebo for each supplement.

The results of the study will potentially provide evidence that these natural supplements can have significant cardioprotective and neuroprotective properties in middle-aged and elderly adults.

Subjects (between 50 and 80 years old) complaining of memory problem who have MMSE (Mini-Mental State Examination) above 27 will be recruited from patients of Dr. Majid Fotuhi (PI at the Neurology Institute for Brain Health and Fitness). Flyers at the institute and advertisement in Baltimore will provide information about the opportunity to enroll in an observational study for 3 months, along with eligibility criteria. Participants will continue to receive routine and standard care, while data on outcome (i.e., dependent) variables and mediators will be collected over three study visits:

Day 1: at the onset of their participation: Assessment of memory and Cardiovascular Fitness Testing (CFT)

Day 2: Blood Test and Transcranial Doppler (TCD) Ultrasound at time 0 and 3 hours after taking the first dose of the supplements;

Month 3: Assessment of memory, Cardiovascular Fitness Testing, and Transcranial Doppler Ultrasound 3 months after daily treatment with supplements in each group.

Eligibility criteria: Inclusion Criteria:

1. Between the ages of 50 and 80;
2. Having a primary care physician;
3. Ability to speak, read, and write English;
4. Logical Memory subtest (of the Wechsler Memory Scale - IV \[WMS-IV\]) raw score one standard deviation or greater below the mean of a younger population;
5. Be in stable overall health based on medical history and physical examination;
6. Sedentary or moderately active (\< 2 aerobic session / week);
7. Suspend, for at least one month before participating in the study, the use of dietary supplements (fish oil, seed oils, ginkgo biloba, ginseng, resveratrol, fruit powder extracts and DHA; subjects who have high intake of these products are asked to take off these products for 4 weeks and after this washout period they will be recruited in the study). No more than one multivitamins per day is acceptable;
8. Wine intake not more than 2 glasses per day

Exclusion Criteria:

1. Patients reporting severe depression with or without suicidal ideation \[Beck Depression Inventory (BDI) \> 30 and BDI item #9 \>1\];
2. Patients with a severe language or hearing and/or vision impairment;
3. Pregnancy;
4. Patients presenting with delirium, dementia, or cognitive impairment (Mini-Mental Status Examination score \< 26);
5. Current alcohol or substance abuse/dependence;
6. Major neurological and psychiatric diseases including Parkinson's disease, Alzheimer's disease, epilepsy, multiple sclerosis, concussion/traumatic brain injury, schizophrenia, bipolar disorder, psychosis, eating disorders;
7. Uncontrolled high blood pressure (\> 180/100 mmHg) or a documented record of uncontrolled high blood pressure-related complications such as cerebral vascular disease (CVD), and/or large strokes with disability, uncontrolled diabetes mellitus (medical report of blood HbA1c \> 7 during the last three months; in diabetic patients without this record HbA1c will be measured in the first blood testing), or history of major cardiopulmonary disease such as congestive heart failure, pulmonary disorders (COPD \[emphysema or chronic bronchitis\] and pulmonary embolism);
8. Documented evidence of the following findings in the current medical history of subjects:

   8-1- Low platelet number (\< 170 x 10\^9/ L); 8-2- Hematocrit below 40% for males or 30% for females; 8-3- Haemoglobin below 120 g/L for males or 110 g/L for females; 8-4- Prothrombin time (PT) values outside normal range of approximately 10-16 s;
9. Current hepatic failure, renal failure, bleeding disorders (hemophilia, Von Willebrand disease, esophageal varicoses);
10. Subjects who have given 500 ml of blood or more for transfusion purposes in the past month before entry into the study
11. Patients who take aspirin more than 325 mg/day
12. Current medications for cognition such as acetylcholine esterase inhibitors (e.g., tacrine, donepezil, galantamine, rivastigmin) and memantine;
13. Known history of allergies to tomatoes or tomato-based products;
14. High habitual intake of tomatoes, grapes, and tomato-based products confirmed by food frequency questionnaire (\>5 times per day). Subjects who have high intake of these products are asked to take off these products for 4 weeks and after this washout period they will be reconsidered to participate in the study.

Primary outcomes:
measure: Evidence of improvement in memory after treatment with Fruitflow-II, resVida (Resveratrol), alone or in combination
timeFrame: 3 months
Secondary outcomes:
measure: Maximal VO2 (VO2 max)
timeFrame: 3 months
measure: Blood Flow to the Brain
timeFrame: 3 months
Other outcomes:
Locations:
city: Lutherville
country: United States
facility: Memosyn Neurology Institute, 1205 York Road, Suite 11
state: Maryland
Study officials:
affiliation: Memosyn Neurology Institute
name: Majid Fotuhi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memosyn Neurology Institute
name: Mehrnoosh Hadadi, MD, MPH
role: STUDY_DIRECTOR
References: