AcAc Di-ester 360mg/kg for Ketosis

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
The Ohio State University, Columbus, OH
Ketosis
Ketone Supplement - DietarySupplement
Eligibility
18 - 65
Male
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Study Summary

One important difference between KE compounds is the ketone-promoting components, which determines the circulating ratio of blood ketone bodies, BHB and AcAc, and may in turn lead to important metabolic and signaling differences. Whereas some actions of the ketone bodies BHB and AcAc are shared, R-BHB has a broad range of signaling functions that are distinct from AcAc, some of which are shared by the non-circulating, non-oxidizable enantiomer, S-BHB. AcAc also has metabolic and signaling actions that are independent of BHB and is selectively oxidized in some cells that cannot oxidize BHB. Furthermore, responses to different ketone bodies vary between tissue types. A second difference between KE arises from the balance between direct delivery of ketones compared to indirectly elevating ketone concentration via metabolism of non-classical or classical ketogenic precursors. Classical ketogenesis itself may drive adaptation and some of the functional benefits associated with ketosis. BDO is included in all of the KE compounds, but it is currently unknown how consumption of BDO alone, and its metabolism via non-classical ketogenesis acutely affects metabolism. Additionally, ketogenesis is now understood to occur in certain cells outside the liver with important local biological effects, for example ketogenesis driven by medium chain fatty acids has been reported in astrocytes in vitro. Provision of systemic BHB by a KE may elicit different biological effects in some tissues such as the brain versus promoting in situ ketogenesis in that tissue. Overall, not only are functional effects of KE incompletely defined, but also it is unknown which effects are common to all KE versus which are specific to an individual KE compound (i.e., BHB Monoester vs AcAc Diester) or which may be attributable to the BDO precursor common to all of the KE. This study will be the first comparative full crossover study of all available KE and the precursor BDO at two serving sizes. Outcomes will focus on established effects of the BHB Monoester (including the effects on ketones, glucose and acid-base balance) and compare these with the effects of the AcAc Diester, C6 Diester and BDO.

Treatment Effectiveness

Study Objectives

1 Primary · 16 Secondary · Reporting Duration: Up to ~ 4 weeks

Week 4
AcAc, R-BHB and S-BHB changes across trials
Acid-Base Balance
Alanine Change
Beverage tolerability questionnaire (BTQ)
Capillary d-BHB concentrations
Continuous Ketone and Glucose Monitoring
Free Fatty Acid Change
Ghrelin
Heart Rate Variability
Insulin
Ketone Excretion
Ketone in breathe expiration
Lactate Change
Respiratory Gas Exchange
Satiety Visual Analogue Scale
Total Plasma Ketone AUC
Whole blood clinical chemistry

Trial Safety

Trial Design

9 Treatment Groups

AcAc Di-ester 360mg/kg
1 of 9
(R)-1,3 butanediol 360mg/kg
1 of 9
C6 Di-ester 360mg/kg
1 of 9
AcAc Di-ester 180mg/kg
1 of 9
(R)-1,3 butanediol 180mg/kg
1 of 9
BHB Mono-ester 180mg/kg
1 of 9
BHB mono-ester 360mg/kg
1 of 9
C6 Di-ester 180mg/kg
1 of 9
Control
1 of 9
Experimental Treatment
Non-Treatment Group

15 Total Participants · 9 Treatment Groups

Primary Treatment: AcAc Di-ester 360mg/kg · Has Placebo Group · N/A

AcAc Di-ester 360mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
(R)-1,3 butanediol 360mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
C6 Di-ester 360mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
AcAc Di-ester 180mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
(R)-1,3 butanediol 180mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
BHB Mono-ester 180mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
BHB mono-ester 360mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
C6 Di-ester 180mg/kgExperimental Group · 7 Interventions: Ketone Supplement, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Other, Other, Behavioral, Biological, Other, Other
ControlPlaceboComparator Group · 8 Interventions: Ketone Supplement, DXA, Urine Analysis, Heart Rate Variability, Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale, Blood Draw, Breath Reading, CGM/CKM · Intervention Types: DietarySupplement, Radiation, Other, Other, Behavioral, Biological, Other, Other
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Blood Draw
2006
Completed Phase 2
~1480

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to ~ 4 weeks

Trial Background

Prof. Jeff Volek, Professor
Principal Investigator
Ohio State University
Closest Location: The Ohio State University · Columbus, OH
Photo of oh the ohio state university  1Photo of oh the ohio state university  2Photo of oh the ohio state university  3
2011First Recorded Clinical Trial
1 TrialsResearching Ketosis
342 CompletedClinical Trials

Eligibility Criteria

Age 18 - 65 · Male Participants · 6 Total Inclusion Criteria

Mark “yes” if the following statements are true for you:
You understand the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator.

About The Reviewer

Michael Gill preview

Michael Gill - B. Sc.

First Published: October 9th, 2021

Last Reviewed: August 12th, 2022

Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.