Motor Cortex Plasticity Response to Theta-Burst Stimulation After Ketone Monoester Supplementation

NCT06799260 | Active Not Recruiting DMC

• 2 other identifiers: JKEUPM-2021-485FRGS/1/2022/SKK01/UPM/02/4
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (1)

• Motor evoked potential (MEP)

  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.

  Pre-TBS (baseline) and post-TBS at 0, 5, 10, 20, and 30 minutes.

Secondary Outcomes (8)

• TMSens_Q questionnaire

  At 30 minutes post-TBS stimulation

• Corticospinal excitability indices

  Pre-KME supplementation and at 1 hour post-KME supplementation

• Blood pressure

  Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and serially thereafter every 3-5 minutes until 30 minutes post-TBS

• Heart rate

  Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and continuously thereafter for 30 minutes post-TBS

• Blood glucose

  Pre-KME supplementation and at 30 minutes post-TBS stimulation

Study Arms (4)

KME then placebo supplement with iTBS stimulation

EXPERIMENTAL

KME drink with iTBS stimulation over the left M1 hand region, followed after a 1-week washout period by a placebo drink with iTBS stimulation over the left M1 hand region

Dietary Supplement: Ketone Monoester (KME); Dietary Supplement: Placebo; Device: iTBS

Placebo then KME supplement with iTBS stimulation

EXPERIMENTAL

Placebo drink with iTBS stimulation over the left M1 hand region, followed after a 1-week washout period by a KME drink with iTBS stimulation over the left M1 hand region

Dietary Supplement: Ketone Monoester (KME); Dietary Supplement: Placebo; Device: iTBS

KME then placebo supplement with cTBS stimulation

EXPERIMENTAL

KME drink with cTBS stimulation over the left M1 hand region, followed after a 1-week washout period by a placebo drink with cTBS stimulation over the left M1 hand region

Dietary Supplement: Ketone Monoester (KME); Dietary Supplement: Placebo; Device: cTBS

Placebo then KME supplement with cTBS stimulation

EXPERIMENTAL

Placebo drink with cTBS stimulation over the left M1 hand region, followed after a 1-week washout period by a KME drink with cTBS stimulation over the left M1 hand region

Dietary Supplement: Ketone Monoester (KME); Dietary Supplement: Placebo; Device: cTBS

Interventions

Ketone Monoester (KME) DIETARY_SUPPLEMENT

500 mg/kg body weight of the KME supplement

KME then placebo supplement with cTBS stimulation; KME then placebo supplement with iTBS stimulation; Placebo then KME supplement with cTBS stimulation; Placebo then KME supplement with iTBS stimulation

Placebo DIETARY_SUPPLEMENT

Taste-matched placebo drink

KME then placebo supplement with cTBS stimulation; KME then placebo supplement with iTBS stimulation; Placebo then KME supplement with cTBS stimulation; Placebo then KME supplement with iTBS stimulation

iTBS DEVICE

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).

KME then placebo supplement with iTBS stimulation; Placebo then KME supplement with iTBS stimulation

cTBS DEVICE

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).

KME then placebo supplement with cTBS stimulation; Placebo then KME supplement with cTBS stimulation

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy young adults (18-35 years old)
• Right-handed
• Fully vaccinated against COVID-19

You may not qualify if:

• 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

Sponsors & Collaborators

• Universiti Putra Malaysia: lead
• University of Oxford: collaborator

Study Sites (1)

Hospital Sultan Abdul Aziz Shah

Serdang, Selangor, 43400, Malaysia

Location

Study Officials

• Wan Aliaa Wan Sulaiman, FRCP

  Universiti Putra Malaysia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 29, 2025
• Study Start: December 18, 2024
• Primary Completion: July 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 25, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

MY (1)