BEAT7: Brain Energy and Aging With Triheptanoin

• Sponsor: Université de Sherbrooke (Other)
• Overall Status: Completed
• CT.gov ID: NCT02679235
• Collaborator: Ultragenyx Pharmaceutical Inc (Industry), Fonds de la Recherche en Santé du Québec (Other)
• Enrollment: 15
• Location: 1
• Arm: 1
• Actual Duration (Months): 28.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Frontal Lobe Hypometabolism	Drug: POST Triheptanoin	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: The participant will receive THN treatment, compared to PRE supplementation condition.The participant will receive THN treatment, compared to PRE supplementation condition.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Brain Energy and Aging With Triheptanoin: The BEAT7 Study
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Aug 8, 2018
• Actual Study Completion Date: Aug 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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.; Other Names: POST THN

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

1. Change in Brain Volumes [28±2 days]

   Structural imaging by T1-weighted MRI to measure brain volume

2. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Centre on Aging (CSSS-IUGS - CIUSSS de l'Estrie - CHUS)	Sherbrooke	Quebec	Canada	J1H4C4

Sponsors and Collaborators

• Université de Sherbrooke
• Ultragenyx Pharmaceutical Inc
• Fonds de la Recherche en Santé du Québec

Investigators

• Principal Investigator: Stephen Cunnane, Ph.D., Research Centre on Aging (CSSS-IUGS - CIUSSS de l'Estrie - CHUS)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 4, 2017

More Information

Publications

None provided.

• Responsible Party: Université de Sherbrooke
• ClinicalTrials.gov Identifier: NCT02679235
• Other Study ID Numbers: 2016-617; 188505
• First Posted: Feb 10, 2016
• Last Update Posted: Jul 23, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No

Study Results

Participant Flow

Arm/Group Title	Triheptanoin
Arm/Group Description	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.
Period Title: Overall Study
STARTED	15
COMPLETED	11
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Triheptanoin
Arm/Group Description	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.
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.9 (2.9)
Sex: Female, Male (Count of Participants)
Female	8 72.7%
Male	3 27.3%
Race and Ethnicity Not Collected (Count of Participants)
Glucose uptake changes estimated by comparing participants' measurements to imaging standards of hea (% of difference compare to young control) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of difference compare to young control]	-14.8 (3.9)
Education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.5 (3.0)
Montreal Cognitive Assessment (MoCA) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	27.3 (2.6)
body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.4 (5.2)

Outcome Measures

1. Primary Outcome

Title	Global Change in Brain Glucose Uptake
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Triheptanoin
Arm/Group Description	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.
Measure Participants	11
PRE	30.3 (1.7)
POST supplementation	30.4 (3.4)

2. Primary Outcome

Title	Global Change in Brain Ketone Uptake
Description	Global change in brain ketone uptake as measured by 11C-acetoacetate PET scans
Time Frame	28±2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Triheptanoin
Arm/Group Description	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.
Measure Participants	11
PRE	0.58 (0.4)
POST supplementation	0.26 (0.2)

3. Secondary Outcome

Title	Change in Brain Volumes
Description	Structural imaging by T1-weighted MRI to measure brain volume
Time Frame	28±2 days

Outcome Measure Data

Analysis Population Description

data was not available for 2 participants

Arm/Group Title	Triheptanoin
Arm/Group Description	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.
Measure Participants	9
hipocampus PRE	7.4 (0.7)
hipocampus POST supplementation	7.4 (0.7)
Amygdala PRE	3.0 (0.5)
Amygdala POST supplementation	3.0 (0.5)
Thalamus PRE	12.8 (1.3)
Thalamus POST suplementation	12.5 (1.2)
Caudate PRE	6.9 (0.8)
Caudate POST supplementation	6.8 (0.7)

4. Secondary Outcome

Title	Change in Cerebral Blood Flow
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Triheptanoin
Arm/Group Description	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.
Measure Participants	11
PRE	41.8 (9.1)
POST supplementation	41.8 (9.4)

Adverse Events

Time Frame	During 4 week supplementation period
Arm/Group Title	Triheptanoin
Arm/Group Description	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.
All Cause Mortality
	Triheptanoin
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Triheptanoin
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Triheptanoin
	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)
Gastrointestinal disorders
severe stomach pain	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.