Brain Energy and Aging With Triheptanoin

Study Overview
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Brief Summary
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BEAT7-001 is a single group study (supplementation). Using a multi-modal brain imaging portfolio, this study will assess whether brain energy metabolism (glucose and ketones), structure or functional connectivity change in older people with frontal glucose hypometabolism after 28 days on an oral dose of 1 g/kg/day of triheptanoin.

Official Title
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Brain Energy and Aging With Triheptanoin: The BEAT7 Study

Conditions
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Frontal Lobe Hypometabolism

Intervention / Treatment
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* Drug: POST Triheptanoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥65 years old; Score ≥26/30 on the Montreal Cognitive Assessment; -≥10% lower brain glucose uptake in the frontal cortex as determined by PET imaging. Exclusion Criteria: Score <26/30 on the Montreal Cognitive Assessment; Medications likely to affect the primary cognitive outcome; Medical or psychiatric conditions that could interfere with study participation (Peterson et al. 2005); Fasting plasma glucose ≥7.0 mM (to avoid recruiting diabetics or pre-diabetics, both of which are risk factors for cognitive impairment in older persons (Mortimer et al. 2010) and also inhibit ketogenesis (Fukao et al. 2004); Clinically-significant gastro-intestinal disease/conditions; Clinically-significant liver disease/dysfunction : ALT ≥37 UI/L, AST ≥36 UI/L, Total bilirubin ≥26 μmol/L; Clinically-significant renal disease/dysfunction : creatinine ≥92 μmol/L, glomerular filtration rate <60 ml/min/1.73 m2 or >90 ml/min/1.73 m2; Clinically-significant cardiac disease/conditions; Clinically-significant abnormal coagulation laboratory results or coagulation disorders at screening; Poorly controlled dyslipidemia (total cholesterol ≥6.2 mmol/L or triglycerides ≥2.20 mmol/L) Hypertension: ≥140/90 mmHg; Substance abuse; Already on MCT supplementation; Visual or hearing impairment impeding comprehension; Non-French speaking; Any condition with life expectancy less than 5 years; Institutionalized or intending to move out of area within 1 year; Participation in other intervention trials.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The participant will receive THN treatment, compared to PRE supplementation condition.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triheptanoin<br>Participant will undergo POST Triheptanoin suppementation 1g/kg body weight for 28 days (dose gradually increased each week, starting at, 0.25, 0.5, 0.75 and then 1 g) separated in 4 doses (with eah meal and before night) after a control PRE supplementation imaging protocol. | Drug: POST Triheptanoin<br>* The target daily dose of triheptanoin will be 1 g/kg/d, or approximately 70 g/d during 28±2 days. It will be divided into four daily doses, one of which will be consumed at each meal and one with an evening snack.<br>* Other names: POST THN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Change in Brain Glucose Uptake | Global change (average of cortex) in brain glucose uptake as measured by 18F-FDG PET scans PRE vs POST 28±2 days of supplementation | 28±2 days | 
| Global Change in Brain Ketone Uptake | Global change in brain ketone uptake as measured by 11C-acetoacetate PET scans | 28±2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brain Volumes | Structural imaging by T1-weighted MRI to measure brain volume | 28±2 days | 
| Change in Cerebral Blood Flow | change in cerebral blood flow measured by arterial spin labeling (ASL) and calculated using a one-compartment model (average cortex) | 28±2 days |