A Clinical Trial to Investigate the Safety and Efficacy of AP-Brain on Cognitive Performance at Varying Dosages in Healthy Middle-aged and Older Adults With Self-reported Memory Problems

A Randomized, Triple-blind, Placebo-controlled, Parallel, Proof of Concept Clinical Trial to Investigate the Safety and Efficacy of AP-Brain on Cognitive Performance at Varying Dosages in Healthy Middle-aged and Older Adults With Self-reported Memory Problems

The goal of this clinical trial is to investigate the safety and efficacy of AP-Brain on cognitive performance at varying dosages in healthy middle-aged and older adults with self-reported memory problems. The main question it aims to answer is:

What is the effect of AP-Brain at 1 g, 3 g, and 5 g on cognitive performance?

Participants will be asked to consume AP-Brain at 1 g, 3 g, or 5g, or Placebo and asked to complete memory assessment questionnaires.

Inclusion Criteria:

1. Males and females 40-79 years of age, inclusive

2. Females not of child-bearing potential, defined as those who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal for at least 1 year prior to screening

   Or,

   Individuals of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

   • Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)
   • Double-barrier method
   • Intrauterine devices
   • Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
   • Vasectomy of partner at least 6 months prior to screening
   • Abstinence and agrees to use contraception if planning on becoming sexually active

3. Individuals with self-reported memory problems as assessed by a combined score of ≥6 from the memory assessment questions provided at screening

4. Absence of dementia or other significant cognitive impairment as assessed by MMSE-2 score of ≥24 at screening

5. Agrees to avoid high sources of caffeine (e.g., supplements, tea, coffee, energy drinks), NSAIDs, and alcohol consumption for 24 hours prior to post-screening clinic visits

6. Agrees to avoid first generation anti-allergy medication for 48 hours prior to post-screening clinic visits

7. Agrees to avoid moderate-vigorous exercise 12 hours prior to post-screening clinic visits

8. Agrees to avoid travel across two or more time zones two weeks prior to any study visit

9. Agrees to maintain current lifestyle habits (diet, physical activity, medications, supplements, and sleep) as much as possible throughout the study

10. Willing and able to complete questionnaires, records, and diaries associated with the study and to complete all clinic visits

11. Provided voluntary, written, informed consent to participate in the study

12. Healthy as determined by medical history, laboratory results, and vital signs, as assessed by the QI

Exclusion Criteria:

1. Individuals who are pregnant, breast feeding, or planning to become pregnant during the study
2. Allergy, sensitivity, or intolerance to the investigational product or placebo ingredients
3. Self-reported confirmation of any significant neuropsychological condition and/or cognitive impairment (e.g., attention-deficit/hyperactivity disorder, Schizophrenia, bipolar disorder, post-traumatic stress disorder, brain injury, neurodegenerative disease, infections, insomnia, depression, epileptic or other seizure-related disorders) that could interfere with study participation as assessed by the QI
4. Self-reported color blindness/weakness as assessed by the QI
5. Individuals who consume high caffeine daily or are addicted to caffeine at screening as assessed by the QI
6. Current employment that calls for overnight shiftwork as assessed by the QI
7. Unstable metabolic disease or chronic diseases as assessed by the QI
8. Current or history of significant diseases of the gastrointestinal tract or conditions that result in malabsorption, as assessed by the QI
9. Unstable hypertension. Treatment on a stable dose of medication for at least 3 months will be considered by the QI (See Section 7.3.1)
10. Type I diabetes
11. Type II diabetes if on insulin treatment. Type II diabetics on stable medication for at least three months and an HbA1c of <8.0% may be included after assessment by the QI on a case-by-case basis
12. Significant cardiovascular event in the past 6 months. Participants with no significant cardiovascular event on stable medication may be included after assessment by the QI on a case-by-case basis
13. History of or current diagnosis with kidney, gallbladder (e.g., gallstones, bile duct obstruction), and/or liver diseases (e.g., reduced bile salts, SIBO) as assessed by the QI on a case-by-case basis, with the exception of history of kidney stones in participants who are symptom free for 6 months
14. Self-reported confirmation of current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI
15. Major surgery in the past 3 months or individuals who have planned surgery during the course of the study. Participants with minor surgery will be considered on a case-by-case basis by the QI
16. Cancer, except skin basal cell carcinoma completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable
17. Individuals with an autoimmune disease or are immune compromised as assessed by the QI
18. Self-reported confirmation of a HIV-, Hepatitis B- and/or C-positive diagnosis as assessed by the QI
19. Self-reported confirmation of blood/bleeding disorders as assessed by QI
20. Use of medical cannabinoid products
21. Chronic use of cannabinoid products (>2 times/week). Occasional users will be required to washout and abstain for the duration of the study period
22. Regular use of tobacco or nicotine products in the past six months, as assessed by the QI. Occasional users will be required to washout and abstain for the duration of the study period
23. Alcohol intake average of >2 standard drinks per day as assessed by the QI
24. Alcohol or drug abuse within the last 12 months
25. Current use of prescribed and/or OTC medications, supplements, and/or consumption of food/drinks that may impact the efficacy and/or safety of the investigational product (Sections 7.3.1 and 7.3.2)
26. Current or previous use of cognitive training programs or therapies, as assessed by the QI
27. Clinically significant abnormal laboratory results at screening as assessed by the QI
28. Blood donation 30 days prior to baseline, during the study, or a planned donation within 30 days of the last study visit
29. Participation in other clinical research studies 30 days prior to baseline, as assessed by the QI
30. Individuals who are cognitively impaired and/or unable to give informed consent
31. Any other condition or lifestyle factor, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant