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

Sponsor

University of British Columbia (Other)

Overall Status

Unknown status

CT.gov ID

NCT02912936

Collaborator

Université de Sherbrooke (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Dietary Supplement: Ketogenic medium chain triglyceride drink (MCT drink) Dietary Supplement: Placebo	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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 [Day 10 of intervention at 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, and 6 hours post MCT dose]
Plasma ketone concentrations of betahydroxybutyrate (BHB) and acetoacetate (AcAc) will be measured in response to MCT dosing from 10-50 grams daily.

Secondary Outcome Measures

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]
To determine the MCT plasma concentration at stated time points in response to MCT dosing from 10-50 grams daily.

Other Outcome Measures

Cerebral metabolic rate of glucose in response to a ketogenic MCT drink [Baseline and day 10 of intervention]
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
Cerebral blood flow in response to a ketogenic MCT drink [Baseline and day 10 of intervention]
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
Changes in MR Spectroscopy (N-acetylaspartate, glutamate, glutamine) in response to a ketogenic MCT drink [Baseline and day 10 of intervention]
Assess changes in brain chemistry (measuring (N-acetylaspartate, glutamate, glutamine) in response to MCT treatment across a dose range of 10-50grams daily
Changes in daily physical activity in response to a ketogenic MCT drink [Baseline and day 10 of intervention]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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