Frontal Lobe Hypometabolism
Conditions
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.
Interventions
DRUGPOST Triheptanoin
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.
Sponsors
Ultragenyx Pharmaceutical Inc
Fonds de la Recherche en Santé du Québec
Université de Sherbrooke
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The participant will receive THN treatment, compared to PRE supplementation condition.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
POST Triheptanoin: 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.
control PRE supplementation: Before supplementation, same participants will undergo imaging protocol as a control condition. Participant will be asked to follow daily normal routine, without any change in medication or food habit. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Triheptanoin | — |
|---|---|---|
| Age, Continuous | 69.9 years STANDARD_DEVIATION 2.9 | — |
| body mass index | 26.4 kg/m^2 STANDARD_DEVIATION 5.2 | — |
| Education | 16.5 years STANDARD_DEVIATION 3 | — |
| Glucose uptake changes estimated by comparing participants' measurements to imaging standards of hea | -14.8 % of difference compare to young control STANDARD_DEVIATION 3.9 | — |
| Montreal Cognitive Assessment (MoCA) | 27.3 scores on a scale STANDARD_DEVIATION 2.6 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
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
Time frame: 28±2 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triheptanoin | Global Change in Brain Glucose Uptake | PRE | 30.3 μmol/100 g/min | Standard Deviation 1.7 |
| Triheptanoin | Global Change in Brain Glucose Uptake | POST supplementation | 30.4 μmol/100 g/min | Standard Deviation 3.4 |
Primary
Global Change in Brain Ketone Uptake
Global change in brain ketone uptake as measured by 11C-acetoacetate PET scans
Time frame: 28±2 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triheptanoin | Global Change in Brain Ketone Uptake | PRE | 0.58 μmol/100 g/min | Standard Deviation 0.4 |
| Triheptanoin | Global Change in Brain Ketone Uptake | POST supplementation | 0.26 μmol/100 g/min | Standard Deviation 0.2 |
Secondary
Change in Brain Volumes
Structural imaging by T1-weighted MRI to measure brain volume
Time frame: 28±2 days
Population: data was not available for 2 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triheptanoin | Change in Brain Volumes | hipocampus PRE | 7.4 ml/100 g/ min | Standard Deviation 0.7 |
| Triheptanoin | Change in Brain Volumes | hipocampus POST supplementation | 7.4 ml/100 g/ min | Standard Deviation 0.7 |
| Triheptanoin | Change in Brain Volumes | Amygdala PRE | 3.0 ml/100 g/ min | Standard Deviation 0.5 |
| Triheptanoin | Change in Brain Volumes | Amygdala POST supplementation | 3.0 ml/100 g/ min | Standard Deviation 0.5 |
| Triheptanoin | Change in Brain Volumes | Thalamus PRE | 12.8 ml/100 g/ min | Standard Deviation 1.3 |
| Triheptanoin | Change in Brain Volumes | Thalamus POST suplementation | 12.5 ml/100 g/ min | Standard Deviation 1.2 |
| Triheptanoin | Change in Brain Volumes | Caudate PRE | 6.9 ml/100 g/ min | Standard Deviation 0.8 |
| Triheptanoin | Change in Brain Volumes | Caudate POST supplementation | 6.8 ml/100 g/ min | Standard Deviation 0.7 |
Secondary
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)
Time frame: 28±2 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triheptanoin | Change in Cerebral Blood Flow | PRE | 41.8 ml/100 g/ min | Standard Deviation 9.1 |
| Triheptanoin | Change in Cerebral Blood Flow | POST supplementation | 41.8 ml/100 g/ min | Standard Deviation 9.4 |