- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06368297
The Effect of Ketone Ester Supplementation and Ketogenic Diet on Brain Plasticity in Overweight/Obese Adults
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 Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Zhaowei Kong, PhD
- Phone Number: 853 8822 8730
- Email: zwkong@um.edu.mo
Study Contact Backup
- Name: Zhen Yuan, PhD
- Phone Number: 853 8822 2314
- Email: zhenyuan@um.edu.mo
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Acute effect of ketone monoester supplementation
To investigate the acute effect of ketone monoester ingestion on brain cortical plasticity using high-frequency rTMS.
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Exogenous ketones are a class of ketone bodies that are ingested using nutritional supplements or foods.
This class of ketone bodies refers to the three water-soluble ketones (acetoacetate, β-hydroxybutyrate [β-HB], and acetone).
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Experimental: Effects of a 2-week ketogenic diet or ketone monoester supplementation
To evaluate the impact of short-term ketogenic dieting and ketone monoester supplementation on brain plasticity. To investigate structural and functional brain adaptations to short-term ketogenic dieting and ketone supplementation. To assess 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. |
Exogenous ketones are a class of ketone bodies that are ingested using nutritional supplements or foods.
This class of ketone bodies refers to the three water-soluble ketones (acetoacetate, β-hydroxybutyrate [β-HB], and acetone).
The ketogenic diet typically reduces total carbohydrate intake to less than 50 grams a day-less than the amount found in a medium plain bagel-and can be as low as 20 grams a day.
Generally, popular ketogenic resources suggest an average of 70-80% fat from total daily calories, 5-10% carbohydrate, and 10-20% protein.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brain Plasticity
Time Frame: 2 weeks
|
This measurement is "brain plasticity".
Brain plasticity, also known as neuroplasticity, refers to the brain's remarkable ability to change and adapt in response to experience.
The brain plasticity will be measured by transcranial magnetic stimulation (TMS) system.
When assessing brain plasticity using TMS through the measurement of Motor Evoked Potentials (MEPs), the primary unit of measurement is typically in millivolts (mV) for the amplitude of the MEPs.
MEPs are electrical signals recorded from muscles after stimulation of the motor cortex with TMS, reflecting the excitability of the corticospinal pathway and, indirectly, cortical plasticity.
|
2 weeks
|
Grey Matter Volume
Time Frame: 2 weeks
|
The measurement name is "grey matter volume", which belongs to brain structure.
The grey matter volume will be assessed by the magnetic resonance imaging system.
Grey matter volume is generally measured in cubic centimeters (cm³) or milliliters (mL), as both units are equivalent in volume measurement (1 cm³ = 1 mL).
This measure reflects the volume of grey matter regions in the brain, which include areas dense with neuronal cell bodies, dendrites, axon terminals, and glial cells.
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2 weeks
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Cortical Thickness
Time Frame: 2 weeks
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The measurement name is "cortical thickness", which belongs to brain structure.
The cortical thickness will be assessed by the magnetic resonance imaging system.
Cortical thickness is measured in millimeters (mm).
It refers to the average thickness of the grey matter cortex across various regions of the brain.
Cortical thickness can vary significantly across different parts of the cortex, typically ranging from around 1 mm to 4 mm, depending on the specific brain region and individual differences.
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2 weeks
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Blood-Oxygen-Level-Dependent (BOLD) Signal Changes
Time Frame: 2 weeks
|
The measurement name is "Blood-Oxygen-Level-Dependent (BOLD) Signal Changes", which belongs to brain function.
The cortical thickness will be assessed by the magnetic resonance imaging system (MRI).
The unit of BOLD signal changes measured by MRI is typically expressed as a percentage change (%).
The BOLD signal reflects changes in the magnetic properties of blood due to variations in oxygenation levels that occur in response to neural activity.
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2 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood Glucose
Time Frame: 6 weeks
|
The measurement name is "blood glucose".
It will be assessed by a glucometer in laboratory settings.
The unit of measurement is millimoles per liter (mmol/L).
|
6 weeks
|
Blood Beta-Hydroxybutyrate
Time Frame: 6 weeks
|
The measurement name is "blood beta-hydroxybutyrate".
It will be assessed by specific ketone meters designed for beta-hydroxybutyrate measurement.
The unit of measurement is millimoles per liter (mmol/L).
|
6 weeks
|
Blood Insulin
Time Frame: 6 weeks
|
The measurement name is "blood insulin".
It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples.
The unit of measurement is microunits per milliliter (μU/mL).
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6 weeks
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Leptin
Time Frame: 6 weeks
|
The measurement name is "leptin".
It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples.
The unit of measurement is nanograms per milliliter (ng/mL).
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6 weeks
|
Ghrelin
Time Frame: 6 weeks
|
The measurement name is "ghrelin".
It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples.
The unit of measurement is picograms per milliliter (pg/mL).
|
6 weeks
|
Brain-Derived Neurotrophic Factor
Time Frame: 6 weeks
|
The measurement name is "brain-derived neurotrophic factor".
It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples.
The unit of measurement is nanograms per milliliter (ng/mL).
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6 weeks
|
Reaction Time of Attention Network Test
Time Frame: 2 weeks
|
The measurement name is "reaction time of Attention Network Test".
The measurement will be assessed by psychological paradigm named Attention Network Test.
The unit of measurement is milliseconds (ms).
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2 weeks
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Accuracy of Attention Network Test
Time Frame: 2 weeks
|
The measurement name is "accuracy of attention network test".
The measurement will be assessed by psychological paradigm named Attention Network Test.
Accuracy is generally measured as a percentage (%).
|
2 weeks
|
Reaction Time of Stroop Task
Time Frame: 2 weeks
|
The measurement name is "reaction time of stroop task".
The measurement will be assessed by psychological paradigm named Stroop Task.
The unit of measurement is milliseconds (ms).
|
2 weeks
|
Accuracy of Stroop Task
Time Frame: 2 weeks
|
The measurement name is "accuracy of stroop task".
The measurement will be assessed by psychological paradigm named Stroop Task.
Accuracy is generally measured as a percentage (%).
|
2 weeks
|
Reaction Time of N-back Task
Time Frame: 2 weeks
|
The measurement name is "reaction time of n-back task".
The measurement will be assessed by psychological paradigm named N-back task.
The unit of measurement is milliseconds (ms).
|
2 weeks
|
Accuracy of N-back Task
Time Frame: 2 weeks
|
The measurement name is "accuracy of n-back task".
The measurement will be assessed by psychological paradigm named N-back task.
Accuracy is generally measured as a percentage (%).
|
2 weeks
|
Cerebral Hemoglobin Concentration
Time Frame: 2 weeks
|
The measurement name is "cerebral hemoglobin concentration".
The measurement will be assessed by functional near-infrared spectroscopy (fNIRS).
The unit of measurement is micromoles per liter (μM).
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2 weeks
|
Height in Kilograms
Time Frame: 2 weeks
|
The measurement name is "height in kilograms".
It will be assessed by a stadiometer.
The unit of measurement is meters (m).
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2 weeks
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Weight in Meters
Time Frame: 2 weeks
|
The measurement name is "weight in meters".
It will be assessed by a scale.
The unit of measurement is kilograms (kg).
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2 weeks
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Body Fat Percentage
Time Frame: 2 weeks
|
The measurement name is "body fat percentage".
It will be assessed by a bioelectrical impedance analysis device.
The unit of measurement is percentage (%).
|
2 weeks
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Fat Mass
Time Frame: 2 weeks
|
The measurement name is "fat mass".
It will be assessed by a bioelectrical impedance analysis device.
The unit of measurement is kilograms (kg).
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2 weeks
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Muscle Mass
Time Frame: 2 weeks
|
The measurement name is "muscle mass".
It will be assessed by a bioelectrical impedance analysis device.
The unit of measurement is kilograms (kg).
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2 weeks
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Body Water
Time Frame: 2 weeks
|
The measurement name is "body water".
It will be assessed by a bioelectrical impedance analysis device.
The unit of measurement is liters (L).
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2 weeks
|
Body Mass Index
Time Frame: 2 weeks
|
The measurement name is "body mass index (BMI)".
It will be assessed by calculating BMI using height and weight measurements obtained from a stadiometer and a scale, respectively.
The unit of measurement is kilograms per square meter (kg/m²).
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2 weeks
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Skinfold Thickness
Time Frame: 2 weeks
|
The measurement name is "skinfold thickness".
It will be assessed by skinfold calipers.
The unit of measurement is millimeters (mm).
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2 weeks
|
Maximal Oxygen Uptake
Time Frame: 2 weeks
|
The measurement name is "maximal oxygen uptake".
It will be assessed by cardiopulmonary exercise testing (CPET) equipment, such as cycle ergometers, along with a metabolic cart for measuring oxygen consumption.
The unit of measurement is milliliters of oxygen per kilogram per minute (mL/kg/min).
|
2 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Zhaowei Kong, PhD, University of Macau
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BSERE22-APP007-FED
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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