Exploratory Trial in Healthy Adults With Mild Cognitive Impairment,16-week Intervention With Mitocholine™

A Randomised, Double-blind, Placebo-controlled, Parallel-group Study in Otherwise Healthy Adults With Mild Cognitive Impairment (MCI) Assessing a 16-week Intervention With Mitocholine™, a Functional Food Ingredient

To evaluate the effect of 16-weeks consumption of Mitocholine on Executive Function and Homocysteine levels in a population experiencing Mild Cognitive Impairment. The study will also include measures of memory, language, S-adenosylmethionone (SAM), Betaine, Choline.

A randomised, double-blind, placebo-controlled, parallel-group study in otherwise healthy adults with Mild Cognitive Impairment (MCI).

Assessing a 16-week intervention with Mitocholine™, a functional food ingredient to evaluate the effect of 16-weeks consumption of Mitocholine on Executive Function and Homocysteine levels in a population experiencing Mild Cognitive Impairment.

The primary hypotheses being that there will be a significant change in Executive Function scores as measured by Delis Kaplan Executive Function Score (DKEFS) and in homocysteine levels.

The study will also include measures of memory, language, S-adenosylmethionone (SAM), Betaine, Choline.

Inclusion Criteria:

1. Willing to participate in the study and comply with its procedures.

2. Able to give written informed consent.

3. Adults aged 55 to 79 years, inclusive.

4. Meet MCI criteria, based on the Peterson criteria (Peterson et al., 1999):

   1. Objective evidence of cognitive impairment as assessed by MoCA (score ≥18 to ≤25).

   2. Absence of major depression as assessed by PHQ (score <10).

   3. Activities of daily living score

      • males ≥4
      • females ≥7

5. Have a homocysteine level ≥11.0μmol/L (Smith D et al, 2018).

Exclusion Criteria:

1. Diagnosis of a major cognitive disorder (e.g. Alzheimer's or Parkinson's disease diagnoses; additionally, confirmation of a mini stroke (TIA) within the last 3 months would be an exclusionary condition).
2. Participants who are pregnant or wish to become pregnant during the trial.
3. Participants who are lactating and/or currently breastfeeding.
4. Participants currently of childbearing potential, but not using an effective method of contraception, as determined by the investigator.
5. Participants with active or a history of alcohol or substance abuse; (exclude elevated Gamma GT & clinically abnormal liver function test).
6. Uncontrolled diabetes (or glycated haemoglobin >7% / 53 mmol/mol).
7. Clinically significant heart, liver, or renal disease (at the discretion of the investigator).
8. Have uncontrolled hypertension SBP > 160mmHg, DBP > 100mmHg).
9. Participants prescribed medications likely to influence memory or mood, as determined by the investigator.
10. Participants with a history of depression (within past 24 months) or any concurrent medical, cognitive or psychiatric condition that would either: compromise his/her ability to comply with the study requirements, may pose significant risk to the participant, or be deemed exclusionary by the investigator
11. Have had any other condition or are taking a medication that the investigator believes would interfere with the objectives of the study, pose a safety risk, or confound the interpretation of the study results.
12. Change in supplements, medication, or major diet in 30 days prior to enrolment and throughout the study.
13. Taking any supplements or vitamins notably known to affect cognitive function (e.g. Living Nutrition Cognitive, Viridian Cognitive Complex, ginkgo biloba, fish oil etc., list not exhaustive), or any psychotropic medications and products which interact with acetylcholine esterase and/or NMDA receptors (6-week washout before screening). Vitamin D and Calcium supplements permitted if on a stable dose for the previous 3 months.
14. Users of inhaled nicotine products such as cigarettes or vape products with an inconsistent recent history of consumption i.e., those who have taken up smoking/vaping in the 12 months prior to screening, or those who have either given up or re-started smoking or vaping in the 12 months prior to screening, or those who intend to significantly modify their use of inhaled nicotine products during their participation in the study.
15. Has received treatment involving experimental drugs in the past 3 months.
16. Have a malignant disease or any concomitant end-stage organ disease, which, in the Investigator's judgment, contraindicates participation in the study.
17. Individuals who, in the opinion of the investigator, are considered to be poor clinical attendees or unlikely for any reason to be able to comply with the trial.
18. Any Participant who is an employee of the study site or an Atlantia Clinical Trials employee or their close family member or a member of their household.