Healthy Young Adult, Neurophysiology
Conditions
Keywords
Transcranial magnetic stimulation, Intermittent theta-burst stimulation, Continuous theta-burst stimulation, Primary motor cortex, Neuroplasticity, ketone monoester, Beta-hydroxybutyrate, Brain-derived neurotrophic factor, Blood pressure, Heart rate
Brief summary
Transcranial magnetic stimulation is a medical device that can alter motor cortical (M1) excitability through the scalp via various protocols. Among these, intermittent- and continuous-theta burst stimulation (iTBS/cTBS) are increasingly used protocols to enhance or suppress M1 excitability, respectively, beyond stimulation. However, the poor reproducibility and high inter-individual variability in responses to TBS protocols are matters of concern. This study will explore whether ketone monoester supplementation can boost TBS efficacy via their mechanistic convergence on Brain-Derived Neurotrophic Factor (BDNF).
Interventions
DIETARY_SUPPLEMENTKetone Monoester (KME)
500 mg/kg body weight of the KME supplement
DIETARY_SUPPLEMENTPlacebo
Taste-matched placebo drink
DEVICEiTBS
iTBS stimulation will be applied using a butterfly figure-of-eight Cool-B70 coil connected to a MagPro R30 stimulator with add-on Theta Burst option (MagVenture A/S, Farum, Denmark).
DEVICEcTBS
cTBS stimulation will be applied using a butterfly figure-of-eight Cool-B70 coil connected to a MagPro R30 stimulator with add-on Theta Burst option (MagVenture A/S, Farum, Denmark).
Sponsors
University of Oxford
Universiti Putra Malaysia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a partial crossover study. The study protocol involves two interventions administered sequentially during each visit: Supplement intervention (KME/placebo) followed after one hour by a stimulation intervention (iTBS/cTBS). There will be two separate groups of subjects undergoing different TBS protocols (iTBS vs cTBS). The subjects of each group will crossover the supplement intervention (KME and placebo) in two visits separated by one week.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy young adults (18-35 years old) * Right-handed * Fully vaccinated against COVID-19
Exclusion criteria
* Subjects with contraindications to TMS based on the screening 13-item questionnaire for TMS safety * Highly active subjects (athletes) * Obese (BMI ≥ 30 kg/m2) * Smokers * Following intermittent fasting or ketogenic diet * Long COVID-19
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor evoked potential (MEP) | Pre-TBS (baseline) and post-TBS at 0, 5, 10, 20, and 30 minutes. | Peak-to-peak MEP amplitude elicited by single-pulse TMS over the left M1 representation of the first dorsal interosseous (FDI) muscle. In each MEP measurement, 12 MEP readings will be collected, elicited by single-pulse TMS at an intensity of 120% resting motor threshold and separated by 15 seconds. In each timepoint post-TBS, the mean value of MEPs (aka, conditioned MEPs) will be averaged and compared to pre-TBS (aka, baseline MEPs) using the following equation: (conditioned MEP amplitude/baseline MEP amplitude) × 100. A value of 90-110 represents no change, while values \< 90% represent suppression and \> 110% facilitation of the M1 plasticity following TBS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and serially thereafter every 3-5 minutes until 30 minutes post-TBS | Systolic blood pressure (SBP), Diastolic Blood Pressure (DBP), and Mean Arterial Pressure (MAP) using fully automated oscillometric sphygmomanometer |
| TMSens_Q questionnaire | At 30 minutes post-TBS stimulation | Self-reported side effects using the TMSens\_Q questionnaire to evaluate the tolerability of the KME-TBS combination. |
| Heart rate | Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and continuously thereafter for 30 minutes post-TBS | Heart rate (bpm) using pulse oximeter |
| Corticospinal excitability indices | Pre-KME supplementation and at 1 hour post-KME supplementation | Resting motor threshold (RMT) followed by motor-evoked potential at 120% RMT intensity |
| Blood beta-hydroxybutyrate | Pre-KME supplementation and at 30 minutes post-TBS stimulation | On-site using a portable glucometer |
| Serum brain-derived neurotrophic factor | Pre-KME supplementation and at 30 minutes post-TBS stimulation | Serum levels of mature brain-derived neurotrophic factor (mBDNF) and pro-BDNF isoforms |
| BDNF genetic polymorphism | At the baseline (pre-KME supplementation) | BDNF rs6265 single nucleotide polymorphism |
| Blood glucose | Pre-KME supplementation and at 30 minutes post-TBS stimulation | On-site using a portable glucometer |
Countries
Malaysia
Outcome results
None listed