A Medium Chain Triglyceride Intervention for Patients With Alzheimer Disease

A Medium Chain Triglyceride INTervention for Alzheimer Disease (A MINT for AD)

The purpose of this study is to determine safety, tolerability, and pharmacokinetics/dynamics of a ketogenic dietary supplement containing medium chain triglycerides (MCTs) in patients with Alzheimer disease (AD). Novel imaging and laboratory biomarkers in response to this intervention will also be explored. In addition, a sub-study was added to the UBC-approved protocol on November 29, 2016, prior to enrollment of the first FTD participant in April 2017. The FTD sub-study was designed as a pilot study to evaluate the safety and tolerability of MCT supplementation in participants with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA).

Inclusion Criteria:

• Diagnosis of mild-moderate Alzheimer disease (AD)
• Mini-Mental State Examination (MMSE) 16-26
• Study partner available who has frequent contact with the participant
• Good visual and auditory acuity for neuropsychological testing
• Education including completion of at least six grades
• Must read and speak English fluently
• Antidepressants permitted, if stable for 4 weeks prior to screening (and participant is not currently depressed and does not have a history of major depression within the past 1 year)
• Cholinesterase inhibitors permitted, if stable for 12 weeks prior to screening

Exclusion Criteria:

• Any significant neurologic disease other than AD
• History of Diabetes Mellitus type I or II
• Any contraindications to MRI or PET studies
• Major depression, bipolar disorder as described within the past 1 year.
• History of schizophrenia
• History of alcohol or substance abuse or dependence within the past 2 years
• Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol
• Current use of specific psychoactive medications
• Investigational amyloid lowering therapies are prohibited two months prior to screening and for the duration of the trial. Other investigational agents are prohibited one month prior to screening and for the duration of the trial.
• History of brain cancer

For FTD-nfvPPA substudy Inclusion Criteria

1. Dx of nonfluent/agrammatic variant primary progressive aphasia

2. Older than 19 years

3. Stability of permitted medications for 4 weeks. In particular, subjects may:

   d. Take stable doses of antidepressants (if they are not currently depressed or do not have a history of major depression within the past 1 year).

   e. Washout from psychoactive medication for at least 4 weeks prior to screening.

   f. Cholinesterase inhibitors are allowable if stable for 12 weeks prior to the screening visit.

4. Study partner is available who has frequent contact with the subject (e.g. an average of 8 hours per week or more), and can accompany the subject to all clinic visits for the duration of the protocol.

5. Females are not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).

6. PET scan consistent with FTD (showing frontal hypoperfusion +/- temporal hypoperfusion)

7. MRI consistent with FTD/PNFA

8. Education including completion of at least six grades

9. Must read and speak English fluently

Exclusion Criteria

1. Any significant neurologic disease other than FTD, such as Alzheimer disease, progressive supranuclear palsy, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, space occupying brain lesion, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
2. History of Diabetes Mellitus type I or II; Hb A1C > 6.0
3. Subjects that have any contraindications to MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, cardiac pacemaker will be excluded from the study, or known bleeding disorder.
4. Major depression, bipolar disorder, or schizophrenia as described in DSM-IV within the past 1 year. Psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol.
5. Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.
6. Current use (sporadic or chronic, within 30 days of screening) of specific psychoactive medications (e.g. typical neuroleptics, narcotic analgesics, anti-Parkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.)
7. Current use of warfarin or other anti-coagulants.
8. Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the Health Canada guidelines
9. AST, ALT, total bilirubin >1.5 times the upper limit of normal;
10. Serum creatinine >1.5 times the upper limit of normal
11. Has a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators.
12. Regular use of MCT products within 30 days of screening. (eg coconut oil, palm oil, coconut milk)
13. History of brain cancer