Clinical trial NCT02771366: The Efficient Brain Study
Official title: The Influence of Fermented Papaya Preparation (FPP) on Cerebral Energy Metabolism, Neuroinflammation, and Cognition in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metabolism - Cerebral Energy
Keywords: neuroinflammation
cognitive function
aging adults
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Osato Research Institute
First posted: 2016-05-13
Enrollment: 30
Sex: ALL
Minimum age (years): 65
Maximum age (years): 100
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Cerebral energy metabolism declines with advanced aging, and is implicated in age-related cognitive decline, Alzheimer's disease (AD), and other forms of neurodegenerative disease (Parkinson's disease). In addition, age-associated increase in systemic and neuroinflammation is associated with a higher likelihood for development of Alzheimer's disease and neurodegenerative disease in older adults. Furthermore, decreased cerebral energy metabolism and increased neuroinflammation are both associated with deficits in cognitive function, even in the absence of neurodegenerative disease. In older adults, decreased cognition is strongly associated with the development of AD, increased rates of hospitalization, loss of functional independence, and increased mortality rate. Novel methods for preventing cognitive decline and neurodegenerative diseases in older adults are needed the world's aging population.

Current research suggests that nutrients in fruits and vegetables produce strong anti-oxidant and anti-proliferative effects. Most Americans are not consuming the minimum recommendations of fruits and vegetables per day to receive these benefits. Whole food-based nutritional products, such as Fermented Papaya Product (FPP), may provide a healthy alternative for individuals. FPP, which is made by bio-fermentation of Carica papaya, has been found to enhance antioxidant protection and to decrease DNA damage in healthy older adults. Furthermore, if FPP increases cerebral energy metabolism and down-regulates neuroinflammation, with resulting effects on cognition, dietary supplementation with FPP may have preventative benefits for age-related cognitive conditions, including MCI, AD, Parkinson's disease and other neurodegenerative diseases.

Detailed description: The design of this research study is to conduct a double-blind, randomized, placebo-controlled pilot study to determine whether FPP improves cerebral energy metabolism, neuroinflammation, systemic inflammation, cognitive function, fatigue, and health-related quality of life in older adults.

Potential participants will participate in a brief 10 minute phone screening that will describe the study. If participants meet initial inclusion/exclusion criteria on the phone screen, they will be scheduled for an in-person screening visit. Participants will attend five (5) in person visits including one Screening Visit performed individually for each potential study participant, and four Assessment Visits (V1-V4). Participants will be asked to provide a fasting blood sample that will be utilized to evaluate clinical laboratory parameters at the Screening visit and all four assessment visits. The participants will complete both a treatment and a placebo condition; therefore, a cross-over design will be used. After eight (8) weeks on each of these regimens, participants will be asked to complete post-treatment outcome assessments at the University of Florida's Institute on Aging - Clinical and Translational Research Building (IOA - CTRB). Following the first post-treatment test day (V2), participants will complete a six (6) week washout period and will then return to the IOA - CTRB to complete the other study arm. The order the participants receive FPP and placebo will be determined through randomization

Eligibility criteria: Inclusion Criteria:

* Willing and able to participate in all aspects of the study;
* Not confined to a wheelchair;
* Evidence of cognitive aging based on Montreal Cognitive Assessment score less than or equal to 28, but greater than or equal to 23;
* Presence of elevated levels of systemic inflammation at screening (C-reactive protein levels \> 1.0)
* Able to swallow study product as directed.

Exclusion Criteria:

* Failure to give consent;
* Active treatment for cancer (\< 3 years);
* Stroke (\< 6 mo);
* Serious heart condition, peripheral vascular disease, coronary artery disease (myocardial infarction\<6 mo), Class III, IV Congestive Heart Failure;
* Dementia (e.g., Alzheimer's disease)
* Severe anemia (Hgb \< 8.0 g/dL);
* Any blood or bleeding disorders;
* Liver or renal disease;
* Diabetes;
* Severe osteoarthritis;
* Anticoagulant therapy (aspirin use is permitted);
* Parkinson's disease;
* Severe psychiatric disease or psychological disorder (e.g., severe depression, bi-polar disorder, schizophrenia) or current use of antipsychotics;
* Current use of anabolic medications (e.g., growth hormone or testosterone) or anticholinesterase inhibitor (i.e., Aricept);
* High amounts of physical activity (i.e., running, bicycling, etc.) \> 120 min/week;
* Excessive alcohol use (\>2 drinks per day);
* Use of tobacco products;
* Resting heart rate \> 120 bpm;
* History of significant head injury leading to cognitive impairments;
* Visual or hearing impairments that would interfere with testing;
* Allergies to papaya or foods with similar compounds (i.e., banana, avocado, kiwi, chestnuts, hazel nuts)
* Allergy to latex;
* Participating in another clinical trial or has received an investigational product within 30 days prior to screening/enrollment;
* Center for Epidemiological Studies - Depression Scale (CES-D) Score \> 20.

Primary outcomes:
measure: Magnetic Resonance Spectroscopy (MRS) Will Measure a Change in Cerebral Energy Function in Brain Tissue
timeFrame: Participants received MRS at weeks 0, 8, 14, and 22. Data reported in the outcome measures data table represents difference between pre and post measurement values (post-pre) for each arm.
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Institute on Aging
state: Florida
Study officials:
affiliation: University of Flrodia
name: Adam Woods, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: