A Medium Chain Triglyceride Intervention for Patients With Alzheimer Disease

NCT02912936 | Completed

• 1 other identifier: H15-02537
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Alzheimer's Disease; Primary Progressive Non-fluent Aphasia; Frontotemporal Dementia (FTD)

Keywords

medium chain triglyceride; MCT; coconut oil; MRI; PET; ketones

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Area under the plasma concentration versus time curve (AUC) of MCT

  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)

  Baseline, Month 3, Month 6

• Change in global functional status (FTLD-CDR-SB)

  Baseline, Month 3, Month 6

• Global clinical impression of change (CGIC)

  Month 3, Month 6

Other Outcomes (4)

• Cerebral metabolic rate of glucose in response to a ketogenic MCT drink

  Baseline and day 10 of intervention

• Cerebral blood flow in response to a ketogenic MCT drink

  Baseline and day 10 of intervention

• Changes in MR Spectroscopy (N-acetylaspartate, glutamate, glutamine) in response to a ketogenic MCT drink

  Baseline and day 10 of intervention

Study Arms (4)

Ketogenic medium chain triglyceride drink

EXPERIMENTAL

Lactose-free skim milk drink containing 25 g of MCT oil per 250 ml.

Dietary Supplement: Ketogenic medium chain triglyceride drink (MCT drink)

Placebo

PLACEBO COMPARATOR

Lactose-free skim milk drink containing high-oleic sunflower oil in the equivalent amount of energy as the active arm.

Dietary Supplement: Placebo

MCT first, then placebo (Sequence A)

EXPERIMENTAL

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); Dietary Supplement: Placebo

Placebo first, then MCT (Sequence B)

EXPERIMENTAL

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); Dietary Supplement: Placebo

Interventions

Ketogenic medium chain triglyceride drink (MCT drink) DIETARY_SUPPLEMENT

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.

Ketogenic medium chain triglyceride drink; MCT first, then placebo (Sequence A); Placebo first, then MCT (Sequence B)

Placebo DIETARY_SUPPLEMENT

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.

MCT first, then placebo (Sequence A); Placebo; Placebo first, then MCT (Sequence B)

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Dx of nonfluent/agrammatic variant primary progressive aphasia
• Older than 19 years
• 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.

Sponsors & Collaborators

• University of British Columbia: lead
• Université de Sherbrooke: collaborator

Study Sites (1)

Djavad Mowafaghian Centre for Brain Health

Vancouver, British Columbia, V6T 1Z3, Canada

Location

MeSH Terms

Conditions

Alzheimer Disease; Primary Progressive Nonfluent Aphasia; Frontotemporal Dementia; Ketosis

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Aphasia, Primary Progressive; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Acidosis; Acid-Base Imbalance

Study Officials

• Haakon Nygaard, MD, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Howard Feldman, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: FTD-nfvPPA substudy: crossover pilot design

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: September 23, 2016
• Study Start: September 1, 2016
• Primary Completion: February 4, 2020
• Study Completion: March 1, 2020
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

CA (1)