Exogenous Ketones and Behavior (ExoKet)

Exogenous Ketones and Behavior (ExoKet)

The study will examine the effect of exogenous ketone ester on behavior and metabolism using Virtual Reality and computerizes behavioral tasks.

Study Overview

• Status: Recruiting
• Conditions: Behavior
• Intervention / Treatment: Dietary supplement: ketone ester; Dietary supplement: dextrose (placebo)

Detailed Description

This study investigates the effects of exogenous ketone ester on behavior, cognition, and metabolism over one week of consumption. Using a within-subjects, randomized, crossover design, participants will undergo two phases: one with the ketone ester supplement and one with a calorie- and taste-matched placebo. The study includes four lab visits: visits 1 and 3 mark the first day of each intervention, while visits 2 and 4 mark the last day. During each visit, participants will complete behavioral tasks, questionnaires, and blood tests. Additionally, participants will record their food intake via an app and collect stool samples throughout the intervention.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Beatrix Keweloh; Phone Number: +49 33200 882518; Email: Beatrix.Keweloh@dife.de
• Study Contact Backup: Name: Soyoung Q Park, Prof.; Email: Soyoung.Park@dife.de

Study Locations

• Germany
  • Brandenburg
    • Potsdam, Brandenburg, Germany, 14558
      • Recruiting
      • German Institute of Human Nutrition
      • Contact: Bianca Weigel; Phone Number: +49 33200 882724; Email: DNN-Studie@dife.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Consent to participate
• Fluent in German
• Physically healthy. No regular medication
• No drug use 1 week prior to the study
• BMI 18-31 kg/m2

Exclusion Criteria:

• Former or current illnesses of:
• Brain or mind (including eating disorders, personality disorders, alcohol, drugs or drug dependence, neurological disorders other than occasional headache; depression or anxiety disorder excluded)
• Heart or blood circulation
• Gastro-intestinal or endocrine disorders
• Liver or kidney disorders
• Electrolyte imbalance
• Other serious past or present medical conditions (for example, metabolic syndrome, diabetes, cancer)
• Pregnancy
• Extreme athletes (>2h/day intense work-out; casual cycling or walking is ok)
• Menopause (post menopause is ok)
• Ketogenic diet, ketogenic supplement intake, intermittent fasting or calorie restricted diet during preceding 4 weeks of study participation
• Fear of blood draw

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ketone ester; Participants consume a ketone ester 3x per day for 8 days.	Dietary supplement: ketone ester; oral supplement
Placebo Comparator: Placebo containing dextrose; Participants consume a placebo 3x per day for 8 days. The placebo is matched in calories and taste to the ketone ester.	Dietary supplement: dextrose (placebo); oral supplement calorie and taste matched to ketone supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety behavior in Virtual Reality	Using different scenes in Virtual Reality, parameters of motion behavior such as speed (measured in meters per second) and distance walked (measured in meters) will be assessed using motion tracking technology. These measurements will be combined to generate a composite score of anxiety-related motion behavior.	on day 8 of each intervention arm (visit 2 and 4)
Risk propensity on a decision-making task	The choice (accept/reject) between a risk/gamble or safe option, based on a task paradigm by Liu et al. (2021)	on day 8 of each intervention arm (visit 2 and 4)
Competitive confidence in a competition task	based on a task paradigm by Goette et al., 2015	on day 8 of each intervention arm (visit 2 and 4)
Delay Discounting behavior in a computerized task	based on a task paradigm by Eisenstein et al. 2015	on day 1 of each intervention arm (visit 1 and 3)
Performance in Dual Task	based on a task paradigm by Szameitat et al., 2002	on day 1 of each intervention arm (visit 1 and 3)
Levels of ketones (ß-Hydroxybutyrate)	Blood samples	baseline, 15, 30, 60, and 90 minutes post drink-consumption on each of the 4 visits
Insulin	Blood samples	baseline, 15, 30, 60, and 90 minutes post drink-consumption on each of the 4 visits
Ghrelin	Blood samples	baseline and + 90 minutes post drink-consumption on each of the 4 visits
Glucose Values	Continuous Glucose Monitoring through sensors applied to skin	every 15 Minutes from visit 1 to visit 2 and again from visit 3 to visit 4
Blood Glucose	Blood samples	baseline, 15, 30, 60, and 90 minutes post drink-consumption on each of the 4 visits
Levels of cortisol	Blood samples	baseline, 15, 30, 60, and 90 minutes post drink-consumption on each of the 4 visits
Electrocardiogram (heart rate)	Electrophysiological recording	between 30 and 60 minutes post drink-consumption on each of the 4 visits
Electrocardiogram (heart rate variability)	Electrophysiological recordings	between 30 and 60 minutes post drink-consumption on each of the 4 visits
Electrodermal Activity	Electrophysiological recordings	between 30 and 60 minutes post drink-consumption on each of the 4 visits
Subjective anxiety levels	reported by participants on visual analog scale (1-7) during Virtual Reality. 1 being no anxiety to 7 being high anxiety	on day 8 of each intervention arm (visit 2 and 4)
Subjective stress levels	reported by participants on visual analog scale (1-7) during Virtual Reality. 1 being no stress to 7 being high stress	on day 8 of each intervention arm (visit 2 and 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome	Assessed via stool samples after each intervention	on day 8 of each intervention arm (visit 2 and 4)
Daily food intake	Self-reported food intake recorded via FoodApp or handwritten food diary	5 days of each intervention arm
Emotional Eating Questionnaire	Salzburg Emotional Eating Scale (SEES; Meule et al. 2018)	baseline (visit 1)
Stress Eating Questionnaire	Salzburg Stress Eating Scale (SSES; Meule et al. 2018)	baseline (visit 1)
Dominance Questionnaire	Social Dominance and Aggressive Dominance Scale (Kalma et al. 1993)	baseline, and on day 8 of each intervention arm (visit 1, 2, and 4)
Autonomy Questionnaire	Basic Psychological Need Satisfaction and Frustration Scale (BPNSNF; Heissel et al. 2019)	on day 8 of each intervention arm (visit 2 and 4)
Personality Questionnaire	Big Five Inventory (BFI; John et al. 1991)	baseline (visit 1)
Stress Questionnaire	Perceived Stress Questionnaire (PSQ; Fliege et al. 2001)	baseline, and on day 8 of each intervention arm (visit 1, 2, and 4)
Subjective anxiety levels	reported via FoodApp once per day	5 days of each intervention arm
Subjective stress levels	reported via FoodApp once per day	5 days of each intervention arm
Trait Anxiety Questionnaire	Trait version of State-Trait Anxiety Inventory (STAI; Grimm et al. 2009). High scores mean high trait anxiety.	baseline before visit 1
State Anxiety Questionnaire	State version of State-Trait Anxiety Inventory (STAI; Grimm et al. 2009). High scores mean high state anxiety.	on day 1 and 8 of each intervention arm (visit 1,2,3,4)
Interoception Questionnaire	Multidimensional Assessment of Interoceptive Awareness (MAIA; Bornemann et al. 2015). High scores mean high interoceptive ability.	on day 8 of each intervention arm (visit 2 and 4)
Depression Questionnaire	Becks Depression Inventar (BDI; Kühner et al. 2007). High scores mean high depression scores	baseline, and on day 8 of each intervention arm (visit 1, 2, and 4)
Mood Questionnaire	Positive and Negative Affect Schedule (PANAS; Janke et al. 2014). High score on positive scale mean high positive mood and high scores on negative scale mean high negative mood.	on day 1 and 8 of each intervention arm (visit 1,2,3,4)
Inhibition Questionnaire	Behavioral Inhibition and Activation (BISBAS; Strobel et al. 2001). High scores on inhibition scale mean high inhibition and high scores on activation scale mean high activation.	baseline (visit 1)
Impulsivity Questionnaire	Barratt Impulsiveness Scale (BIS; Barratt et al. 1965). High scores mean high impulsivity.	baseline (visit 1)
Social Anxiety Questionnaire	Liebowitz Social Anxiety Scale (Heimberg et al. 1999). High scores mean high scoial anxiety	baseline, and on day 8 of each intervention arm (visit 1, 2, and 4)
Flow Questionnaire	Flow state scale (FSS; Rheinberg et al. 2002) asked after Dual Task. High scores mean more flow experience during the dual task.	on day 1 of each intervention arm (visit 1 and 3)
Chronotype Questionnaire	Morningness-Eveningness Questionnaire (MEQ; Horne & Östberg, 1976)	baseline (visit 1)

Collaborators and Investigators

• Sponsor: German Institute of Human Nutrition

Publications and helpful links

General Publications

• Liu L, Artigas SO, Ulrich A, Tardu J, Mohr PNC, Wilms B, Koletzko B, Schmid SM, Park SQ. Eating to dare - Nutrition impacts human risky decision and related brain function. Neuroimage. 2021 Jun;233:117951. doi: 10.1016/j.neuroimage.2021.117951. Epub 2021 Mar 12.
• Eisenstein SA, Gredysa DM, Antenor-Dorsey JA, Green L, Arbelaez AM, Koller JM, Black KJ, Perlmutter JS, Moerlein SM, Hershey T. Correction: Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity. PLoS One. 2016 Jan 8;11(1):e0147063. doi: 10.1371/journal.pone.0147063. eCollection 2016. No abstract available.
• Goette L, Bendahan S, Thoresen J, Hollis F, Sandi C. Stress pulls us apart: anxiety leads to differences in competitive confidence under stress. Psychoneuroendocrinology. 2015 Apr;54:115-23. doi: 10.1016/j.psyneuen.2015.01.019. Epub 2015 Feb 19.

Study record dates

Study Major Dates

• Study Start (Estimated): July 18, 2024
• Primary Completion (Estimated): June 23, 2025
• Study Completion (Estimated): June 23, 2025

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: anxiety; intervention; metabolism; ketones; human cognition
• Other Study ID Numbers: ExoKet

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No