Clinical trial NCT06799260: Motor Cortex Plasticity Response to Theta-Burst Stimulation After Ketone Monoester Supplementation
Official title: Priming Effects of Ketone Monoester Supplementation on Theta-Burst Stimulation-Induced Plasticity in the Primary Motor Cortex
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Healthy Young Adult
Neurophysiology
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
Lead sponsor: Universiti Putra Malaysia
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2025-01-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: BASIC_SCIENCE

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).


Eligibility criteria: 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

Primary outcomes:
measure: Motor evoked potential (MEP)
timeFrame: Pre-TBS (baseline) and post-TBS at 0, 5, 10, 20, and 30 minutes.
Secondary outcomes:
measure: TMSens_Q questionnaire
timeFrame: At 30 minutes post-TBS stimulation
measure: Corticospinal excitability indices
timeFrame: Pre-KME supplementation and at 1 hour post-KME supplementation
measure: Blood pressure
timeFrame: Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and serially thereafter every 3-5 minutes until 30 minutes post-TBS
measure: Heart rate
timeFrame: Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and continuously thereafter for 30 minutes post-TBS
measure: Blood glucose
timeFrame: Pre-KME supplementation and at 30 minutes post-TBS stimulation
measure: Blood beta-hydroxybutyrate
timeFrame: Pre-KME supplementation and at 30 minutes post-TBS stimulation
measure: Serum brain-derived neurotrophic factor
timeFrame: Pre-KME supplementation and at 30 minutes post-TBS stimulation
measure: BDNF genetic polymorphism
timeFrame: At the baseline (pre-KME supplementation)
Other outcomes:
Locations:
city: Serdang
country: Malaysia
facility: Hospital Sultan Abdul Aziz Shah
state: Selangor
Study officials:
affiliation: Universiti Putra Malaysia
name: Wan Aliaa Wan Sulaiman, FRCP
role: STUDY_CHAIR
References: