Clinical trial NCT06368297: The Effect of Ketone Ester Supplementation and Ketogenic Diet on Brain Plasticity in Overweight/Obese Adults
Official title: The Effect of Ketone Ester Supplementation and Ketogenic Diet on Brain Plasticity in Overweight/Obese Adults: A Neurophysiological and Resting Functional Magnetic Resonance Study (rfMRI)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Overweight and Obesity
Cognitive Change
Psychophysiologic Reaction
Keywords: Overweight
Obesity
Ketone
Neurocognition
Lead sponsor: University of Macau
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This project comprises an initial crossover placebo-controlled neurophysiological study to ascertain the effect of acute ketone ester ingestion on motor cortex plasticity, followed by a second 2-week intervention study aimed to compare the effect of a ketogenic diet versus ketone ester supplementation on motor cortex plasticity, resting brain function and structure, and metabolic and neuroendocrine responses.

Detailed description: The study initially makes a bold attempt to explore whether the ketone supplementation would induce improvements in the overweight/ obese population's brain health via altering motor cortex plasticity, brain function and structure, and metabolic and neuroendocrine pathways. The study's aims include:

* assessing changes in brain plasticity associated with excessive body weight and/or obesity.
* evaluating the potential of ketone monoester supplementation in enhancing brain plasticity.
* evaluating the potential of ketone monoester supplementation in correcting impaired brain plasticity due to excessive body weight.
* evaluating the impact of short-term ketogenic dieting and ketone monoester supplementation on brain plasticity.
* investigating structural and functional brain adaptations to short-term ketogenic dieting and ketone supplementation.
* assessing the relationship between changes in brain plasticity and the brain's structural and functional adaptations and changes in circulating levels of brain-derived neurotrophic factors and key central acting hormones (i.e., insulin and leptin) due to ketogenic dieting and ketone monoester supplementation.

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) \> 25 and \< 35 kg/m2 (overweight/obese group) or BMI \> 18.5 and \< 25 kg/m2 (healthy weight group);
* Right-handed.

Exclusion Criteria:

* Presenting any established counter indication for transcranial magnetic stimulation;
* Currently taking any medication affecting the central or the peripheral nervous system;
* Suffering from any psychiatric, neurologic, cardiovascular, or metabolic disease, including type 1 and type 2 diabetes mellitus;
* Undertaking surgery in the past six months;
* Engaged in resistance training.
* Pregnancy;
* Breastfeeding;
* Being amenorrhea.

Primary outcomes:
measure: Brain Plasticity
timeFrame: 2 weeks
measure: Grey Matter Volume
timeFrame: 2 weeks
measure: Cortical Thickness
timeFrame: 2 weeks
measure: Blood-Oxygen-Level-Dependent (BOLD) Signal Changes
timeFrame: 2 weeks
Secondary outcomes:
measure: Blood Glucose
timeFrame: 6 weeks
measure: Blood Beta-Hydroxybutyrate
timeFrame: 6 weeks
measure: Blood Insulin
timeFrame: 6 weeks
measure: Leptin
timeFrame: 6 weeks
measure: Ghrelin
timeFrame: 6 weeks
measure: Brain-Derived Neurotrophic Factor
timeFrame: 6 weeks
measure: Reaction Time of Attention Network Test
timeFrame: 2 weeks
measure: Accuracy of Attention Network Test
timeFrame: 2 weeks
measure: Reaction Time of Stroop Task
timeFrame: 2 weeks
measure: Accuracy of Stroop Task
timeFrame: 2 weeks
measure: Reaction Time of N-back Task
timeFrame: 2 weeks
measure: Accuracy of N-back Task
timeFrame: 2 weeks
measure: Cerebral Hemoglobin Concentration
timeFrame: 2 weeks
measure: Height in Kilograms
timeFrame: 2 weeks
measure: Weight in Meters
timeFrame: 2 weeks
measure: Body Fat Percentage
timeFrame: 2 weeks
measure: Fat Mass
timeFrame: 2 weeks
measure: Muscle Mass
timeFrame: 2 weeks
measure: Body Water
timeFrame: 2 weeks
measure: Body Mass Index
timeFrame: 2 weeks
measure: Skinfold Thickness
timeFrame: 2 weeks
measure: Maximal Oxygen Uptake
timeFrame: 2 weeks
Other outcomes:
Locations:
Study officials:
affiliation: University of Macau
name: Zhaowei Kong, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Falkenhain K, Daraei A, Forbes SC, Little JP. Effects of Exogenous Ketone Supplementation on Blood Glucose: A Systematic Review and Meta-analysis. Adv Nutr. 2022 Oct 2;13(5):1697-1714. doi: 10.1093/advances/nmac036.
citation: Evans M, McClure TS, Koutnik AP, Egan B. Exogenous Ketone Supplements in Athletic Contexts: Past, Present, and Future. Sports Med. 2022 Dec;52(Suppl 1):25-67. doi: 10.1007/s40279-022-01756-2. Epub 2022 Oct 10.
citation: Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P, D'Agostino DP. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond). 2016 Feb 4;13:9. doi: 10.1186/s12986-016-0069-y. eCollection 2016.
citation: Walsh JJ, Neudorf H, Little JP. 14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1738-e1754. doi: 10.1210/clinem/dgaa925.