A Medium Chain Triglyceride Intervention for Patients With Alzheimer Disease (MINT-01)

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease; Frontotemporal Dementia (FTD); Primary Progressive Non-fluent Aphasia
• Intervention / Treatment: Dietary supplement: Ketogenic medium chain triglyceride drink (MCT drink); Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • Djavad Mowafaghian Centre for Brain Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic medium chain triglyceride drink; Lactose-free skim milk drink containing 25 g of MCT oil per 250 ml.	Dietary supplement: Ketogenic medium chain triglyceride drink (MCT drink); 10 days supplementation with the MCT drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.
Placebo Comparator: Placebo; Lactose-free skim milk drink containing high-oleic sunflower oil in the equivalent amount of energy as the active arm.	Dietary supplement: Placebo; 10 days supplementation with the placebo drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.
Experimental: MCT first, then placebo (Sequence A); Participants received SCCF-3012 (ketogenic medium-chain triglyceride emulsion, 15 g twice daily = 30 g/day total) for 3 months during Period 1, followed by placebo (high-oleic sunflower oil, energy-matched) for 3 months during Period 2. No washout period between phases. Applies to MINT-FTD sub-study cohort only.	Dietary supplement: Ketogenic medium chain triglyceride drink (MCT drink); 10 days supplementation with the MCT drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.; Dietary supplement: Placebo; 10 days supplementation with the placebo drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.
Experimental: Placebo first, then MCT (Sequence B); Participants received placebo (high-oleic sunflower oil, energy-matched) for 3 months during Period 1, followed by SCCF-3012 (ketogenic medium-chain triglyceride emulsion, 15 g twice daily = 30 g/day total) for 3 months during Period 2. No washout period between phases. Applies to MINT-FTD sub-study cohort only.	Dietary supplement: Ketogenic medium chain triglyceride drink (MCT drink); 10 days supplementation with the MCT drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.; Dietary supplement: Placebo; 10 days supplementation with the placebo drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events, serious adverse events		From baseline to day 10 of intervention
Plasma ketone concentrations in response to ascending dose of MCT	Plasma ketone concentrations of betahydroxybutyrate (BHB) and acetoacetate (AcAc) will be measured in response to MCT dosing from 10-50 grams daily.	Day 10 of intervention at 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, and 6 hours post MCT dose
Safety and tolerability of SCCF-3012	Incidence of treatment-emergent adverse events, serious adverse events, and laboratory parameter changes during 3 months of continuous SCCF-3012 dosing at 30 g/day (15 g BID) in participants with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Adverse events tabulated by severity (mild/moderate/severe) and relatedness to study intervention (unlikely/possible/probable/likely). Tolerability assessed by the proportion of participants able to complete 3 months of continuous dosing at the target dose without intervention-related discontinuation.	Baseline to Month 6
Pharmacodynamic ketone response	Plasma β-hydroxybutyrate (BHB) concentration in FTD-nfvPPA participants at pre-dose, 1 hour, and 4 hours following ingestion of the study drink, measured at the end of each 3-month phase. Primary pharmacodynamic endpoint is the 4-hour post-dose plasma BHB at the end of the MCT phase.	Baseline, Month 3, Month 6 (each at pre-dose, 1 hour, and 4 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) of MCT	To determine the MCT plasma concentration at stated time points in response to MCT dosing from 10-50 grams daily.	Day 10 of intervention at 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, and 6 hours post MCT dose
Change in language function (WAB-R Part 1)	For FTD-nfvPPA, Western Aphasia Battery-Revised Part I Aphasia Quotient (AQ; range 0-100, higher = better language function). Administered by a blinded examiner. Within-subject change analyzed as end-of-MCT-phase AQ minus end-of-placebo-phase AQ.	Baseline, Month 3, Month 6
Change in global functional status (FTLD-CDR-SB)	Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR-SB), extended from the standard CDR with language and behaviour modules. Range 0-24, with higher scores indicating greater impairment. Within-subject change analyzed as end-of-MCT-phase minus end-of-placebo-phase.	Baseline, Month 3, Month 6
Global clinical impression of change (CGIC)	Clinician Global Impression of Change (7-point scale: 1 = very much improved to 7 = very much worse), rated by a study clinician blinded to treatment allocation. At each follow-up visit, rating reflects change relative to the immediately preceding assessment (3-month phase) and is attributable to the treatment received during that phase.	Month 3, Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral metabolic rate of glucose in response to a ketogenic MCT drink	Assess changes in metabolic rate of glucose by 18F fludeoxyglucose positron emission tomography (FDG-PET) in response to escalating doses of MCT (10-50grams daily) in patients with Alzheimer's disease	Baseline and day 10 of intervention
Cerebral blood flow in response to a ketogenic MCT drink	Assess changes in brain blood flow using MRI (Arterial Spin Labeling) in response to escalating doses of MCT (10-50 grams daily) in patients with Alzheimer's disease	Baseline and day 10 of intervention
Changes in MR Spectroscopy (N-acetylaspartate, glutamate, glutamine) in response to a ketogenic MCT drink	Assess changes in brain chemistry (measuring (N-acetylaspartate, glutamate, glutamine) in response to MCT treatment across a dose range of 10-50grams daily	Baseline and day 10 of intervention
Changes in daily physical activity in response to a ketogenic MCT drink	Changes in behavior rhythms (activity level and sleep/rest) in response to MCT treatment across a dose range of 10-50grams daily, using an actigraphy watch.	Baseline and day 10 of intervention

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Université de Sherbrooke
• Investigators: Principal Investigator: Haakon Nygaard, MD, PhD, University of British Columbia; Principal Investigator: Howard Feldman, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): February 4, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: September 22, 2016
• First Posted (Estimated): September 23, 2016

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: MRI; PET; ketones; coconut oil; MCT; medium chain triglyceride
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Communication Disorders; Language Disorders; Aphasia; Speech Disorders; Frontotemporal Lobar Degeneration; Acid-Base Imbalance; Acidosis; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Aphasia, Primary Progressive; Alzheimer Disease; Frontotemporal Dementia; Ketosis; Primary Progressive Nonfluent Aphasia
• Other Study ID Numbers: H15-02537

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No