Brain Energy and Aging With Triheptanoin

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Triheptanoin	POST Triheptanoin	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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