Healthy Young AdultKME-TBSNCT06799260
Motor Cortex Plasticity Response to Theta-Burst Stimulation After Ketone Monoester Supplementation
A study testing Ketone Monoester (KME), iTBS and cTBS in people with Healthy Young Adult and Neurophysiology, run by Universiti Putra Malaysia at 1 site in Malaysia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Young Adult, Neurophysiology
- What is being tested?
- Ketone Monoester (KME), iTBS and cTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteMalaysia
- Study dates
- 18 Dec 2024to 1 Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy young adults (18-35 years old)
- Right-handed
- Fully vaccinated against COVID-19
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Priming Effects of Ketone Monoester Supplementation on Theta-Burst Stimulation-Induced Plasticity in the Primary Motor Cortex
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
- Being tested
- Ketone Monoester (KME), Placebo, iTBS, cTBS
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone Monoester (KME)Dietary supplement
500 mg/kg body weight of the KME supplement
PlaceboDietary supplement
Taste-matched placebo drink
iTBSDevice
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).
cTBSDevice
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Dietary Supplement: Ketone Monoester (KME); Dietary Supplement: Placebo; Device: cTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Pre-TBS (baseline) and post-TBS at 0, 5, 10, 20, and 30 minutes.
Secondary outcomes (8)
TMSens_Q questionnaire
Self-reported side effects using the TMSens_Q questionnaire to evaluate the tolerability of the KME-TBS combination.
Measured: At 30 minutes post-TBS stimulation
Corticospinal excitability indices
Resting motor threshold (RMT) followed by motor-evoked potential at 120% RMT intensity
Measured: Pre-KME supplementation and at 1 hour post-KME supplementation
Blood pressure
Systolic blood pressure (SBP), Diastolic Blood Pressure (DBP), and Mean Arterial Pressure (MAP) using fully automated oscillometric sphygmomanometer
Measured: Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and serially thereafter every 3-5 minutes until 30 minutes post-TBS
Heart rate
Heart rate (bpm) using pulse oximeter
Measured: Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and continuously thereafter for 30 minutes post-TBS
Blood glucose
On-site using a portable glucometer
Measured: Pre-KME supplementation and at 30 minutes post-TBS stimulation
Blood beta-hydroxybutyrate
On-site using a portable glucometer
Measured: Pre-KME supplementation and at 30 minutes post-TBS stimulation
Serum brain-derived neurotrophic factor
Serum levels of mature brain-derived neurotrophic factor (mBDNF) and pro-BDNF isoforms
Measured: Pre-KME supplementation and at 30 minutes post-TBS stimulation
BDNF genetic polymorphism
BDNF rs6265 single nucleotide polymorphism
Measured: At the baseline (pre-KME supplementation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start18 Dec 2024
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Young AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universiti Putra Malaysia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Principal investigator, Wan Aliaa Wan Sulaiman, Universiti Putra Malaysia
- Investigators
- Wan Aliaa Wan Sulaiman, FRCP, Study chair, Universiti Putra Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06799260
- Sponsor's protocol ID
- JKEUPM-2021-485
- Other IDs
- FRGS/1/2022/SKK01/UPM/02/4
- Acronym
- KME-TBS
- Status last verified
- Dec 2024
- First submitted
- 2 Jan 2025
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified raw datasets collected during the trial will be freely available upon completion on the Open Science Framework repository at https://osf.io/
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Priming Effects of Ketone Monoester Supplementation on Theta-Burst Stimulation-Induced Plasticity in the Primary Motor Cortex
- ClinicalTrials.gov ID
- NCT06799260
- Acronym / sponsor ID
- KME-TBS / JKEUPM-2021-485
- 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
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Universiti Putra MalaysiaUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 18 Dec 2024 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 29 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| KME then placebo supplement with iTBS stimulation | Experimental | Dietary Supplement: Ketone Monoester (KME), Dietary Supplement: Placebo, Device: iTBSKME 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 |
| Placebo then KME supplement with iTBS stimulation | Experimental | Dietary Supplement: Ketone Monoester (KME), Dietary Supplement: Placebo, Device: iTBSPlacebo 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 |
| KME then placebo supplement with cTBS stimulation | Experimental | Dietary Supplement: Ketone Monoester (KME), Dietary Supplement: Placebo, Device: cTBSKME 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 |
| Placebo then KME supplement with cTBS stimulation | Experimental | Dietary Supplement: Ketone Monoester (KME), Dietary Supplement: Placebo, Device: cTBSPlacebo 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 |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy young adults (18-35 years old)
- Right-handed
- Fully vaccinated against COVID-19
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketone Monoester (KME)500 mg/kg body weight of the KME supplement | Dietary 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 |
| PlaceboTaste-matched placebo drink | Dietary 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 |
| iTBSiTBS 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). | Device | KME then placebo supplement with iTBS stimulation, Placebo then KME supplement with iTBS stimulation |
| cTBScTBS 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). | Device | KME then placebo supplement with cTBS stimulation, Placebo then KME supplement with cTBS stimulation |
Primary outcome
Motor evoked potential (MEP)
Time frame: 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.
8 secondary outcomes
TMSens_Q questionnaire
Time frame: At 30 minutes post-TBS stimulation
Corticospinal excitability indices
Time frame: Pre-KME supplementation and at 1 hour post-KME supplementation
Blood pressure
Time frame: Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and serially thereafter every 3-5 minutes until 30 minutes post-TBS
Heart rate
Time frame: Pre-supplementation, at 1 hour post-supplementation/pre-TBS stimulation, and continuously thereafter for 30 minutes post-TBS
Blood glucose
Time frame: Pre-KME supplementation and at 30 minutes post-TBS stimulation
Blood beta-hydroxybutyrate
Time frame: Pre-KME supplementation and at 30 minutes post-TBS stimulation
Serum brain-derived neurotrophic factor
Time frame: Pre-KME supplementation and at 30 minutes post-TBS stimulation
BDNF genetic polymorphism
Time frame: At the baseline (pre-KME supplementation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Individual participant dataSharing planned: Yes. Deidentified raw datasets collected during the trial will be freely available upon completion on the Open Science Framework repository at https://osf.io/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wan Aliaa Wan Sulaiman, FRCP study chair
Universiti Putra Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone Monoester (KME), iTBS and cTBS in people with Healthy Young Adult and Neurophysiology, run by Universiti Putra Malaysia at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motor evoked potential (MEP) (time frame: Pre-TBS (baseline) and post-TBS at 0, 5, 10, 20, and 30 minutes.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.