Trial Outcomes & Findings for Effects of L-theanine on Motor Cortex Excitability in Healthy Subjects: A Paired-Pulse TMS Study (NCT NCT04749745)

Last Updated: 2021-09-23

Results Overview

The changes of Short-interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), and Long-interval Intracortical Inhibition (LICI) before and 30 minutes after each drug administration. SICI, ICF and LICI are paired-pulse TMS (ppTMS)-EMG outcome measures that assess the activity of motor cortex GABA-A, NMDA and GABA-B interneurons, respectively. They are measured by the ratio between the peak-to-peak amplitude of motor-evoked potential (MEP) elicited by a testing TMS pulse (120% of the intensity of the resting motor threshold, following a conditioning pulse at different inter-stimuli interval, 2-5 milliseconds for SICI, 10-20 milliseconds for ICF, 100-200 milliseconds for LICI) and the peak-to-peak MEP amplitude elicited by a single pulse (120% of the intensity of the resting motor threshold). The baseline-to-post-drug change of SICI, ICF and LICI elicited by L-theanine will be compared to that elicited by placebo within each subject.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

11 participants

Primary outcome timeframe

Before and 30 minutes after each drug administration (no long-term follow up as this is a study on acute effect of a single-dose agent).

Results posted on

2021-09-23

Participant Flow

We screened and enrolled 11 subjects altogether. 10 subjects in total completed the study. As this is a cross-over study, so each arm has 10 subjects.

Participant milestones

Participant milestones
Measure	L-Theanine First, Then Placebo Subject will receive 400mg single dose of L-theanine, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. L-theanine: The subject will receive paired-pulse TMS (ppTMS) procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface electromyogram (EMG). The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered by the coil, the EMG over a thumb muscle (abductor pollicis brevis) will record a motor-evoked potential on the tracing. Cross-over with placebo in two separate sessions at least 72 hours apart. Placebo: The subject will receive ppTMS procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface electromyogram (EMG). The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered, the EMG over the abductor pollicis brevis will record a motor-evoked potential on the tracing. Cross-over with L-theanine in two separate sessions at least 72 hours apart.	Placebo First, Then L-Theanine Subject will receive 400mg single dose of matching Placebo, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. L-theanine: The subject will receive paired-pulse TMS (ppTMS) procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface electromyogram (EMG). The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered by the coil, the EMG over a thumb muscle (abductor pollicis brevis) will record a motor-evoked potential on the tracing. Cross-over with placebo in two separate sessions at least 72 hours apart. Placebo: The subject will receive ppTMS procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface EMG. The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered by the coil, the EMG over the abductor pollicis brevis will record a motor-evoked potential on the tracing. Cross-over with L-theanine in two separate sessions at least 72 hours apart.
Overall Study STARTED	5	6
Overall Study First Intervention	4	6
Overall Study Washout	4	6
Overall Study Second Intervention	4	6
Overall Study COMPLETED	4	6
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	L-Theanine First, Then Placebo Subject will receive 400mg single dose of L-theanine, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. L-theanine: The subject will receive paired-pulse TMS (ppTMS) procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface electromyogram (EMG). The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered by the coil, the EMG over a thumb muscle (abductor pollicis brevis) will record a motor-evoked potential on the tracing. Cross-over with placebo in two separate sessions at least 72 hours apart. Placebo: The subject will receive ppTMS procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface electromyogram (EMG). The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered, the EMG over the abductor pollicis brevis will record a motor-evoked potential on the tracing. Cross-over with L-theanine in two separate sessions at least 72 hours apart.	Placebo First, Then L-Theanine Subject will receive 400mg single dose of matching Placebo, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. L-theanine: The subject will receive paired-pulse TMS (ppTMS) procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface electromyogram (EMG). The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered by the coil, the EMG over a thumb muscle (abductor pollicis brevis) will record a motor-evoked potential on the tracing. Cross-over with placebo in two separate sessions at least 72 hours apart. Placebo: The subject will receive ppTMS procedure before and 30min after taking the drug orally, to assess motor cortex excitability, measured by surface EMG. The ppTMS procedure is administered by a TMS stimulator controlled a software named Signal. The coil of the stimulator is placed above the scalp where the stimulation would activate the left primary motor cortex region that controls the right thumb. When a pulse is delivered by the coil, the EMG over the abductor pollicis brevis will record a motor-evoked potential on the tracing. Cross-over with L-theanine in two separate sessions at least 72 hours apart.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Effects of L-theanine on Motor Cortex Excitability in Healthy Subjects: A Paired-Pulse TMS Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	L-Theanine and Placebo Cross-over in All Subjects n=10 Participants Subject will receive 400mg single dose of L-theanine or Placebo, by oral ingestion with water. After 72 hours washout period, the same subject will then receive 400mg single dose of Placebo or L-theanine (opposite condition from the first dose). The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. All subjects receive both conditions of drugs.
Age, Continuous	29.5 years STANDARD_DEVIATION 3.2 • n=99 Participants
Sex: Female, Male Female	5 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	3 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	7 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Body Mass Index (BMI)	23.7 kg/m^2 STANDARD_DEVIATION 3.1 • n=99 Participants
Handedness (Right)	10 Participants n=99 Participants
Multilingual	3 Participants n=99 Participants
Years of Education	20.8 years STANDARD_DEVIATION 2.4 • n=99 Participants
Average Sleep Hours	7.4 Hours STANDARD_DEVIATION 0.6 • n=99 Participants
Daily Coffee Drinker	6 Participants n=99 Participants

PRIMARY outcome

Timeframe: Before and 30 minutes after each drug administration (no long-term follow up as this is a study on acute effect of a single-dose agent).

Population: This is a cross-over study, therefore each subject will receive the drug conditions in both arms. The outcomes will be compared using Wilcoxon Signed-rank test to see if L-theanine elicits different changes of SICI, ICF or LICI within each individual than placebo does.

Outcome measures

Outcome measures
Measure	L-Theanine n=10 Participants Subject will receive 400mg single dose of L-theanine, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. The baseline-to-post-drug change of SICI, ICF and LICI elicited by L-theanine will be compared to that elicited by placebo within each subject.	Placebo n=10 Participants Subject will receive 400mg single dose of matching Placebo, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded. The baseline-to-post-drug change of SICI, ICF and LICI elicited by L-theanine will be compared to that elicited by placebo within each subject.
The Change of Motor Cortex Excitability Measures by ppTMS SICI	0.059 Ratio Standard Error 0.028	0.005 Ratio Standard Error 0.060
The Change of Motor Cortex Excitability Measures by ppTMS LICI	0.145 Ratio Standard Error 0.100	-0.068 Ratio Standard Error 0.053
The Change of Motor Cortex Excitability Measures by ppTMS ICF	0.073 Ratio Standard Error 0.073	-0.341 Ratio Standard Error 0.176

SECONDARY outcome

Timeframe: Throughout each session; each session lasts up to 3 hours; 2 sessions for each subject. The 2 sessions are 3-7 days apart.

VAS is a quick scale to assess and track how the participant subjectively feels through out each study session, e.g. anxiety, depression, excitement, etc. The score for each word ranges from "0" being the least in your life and "100" being the most in your life. It takes 3-4 minutes to complete each VAS, and there are 4 takes of VAS during each session. The outcome measure is the change of VAS throughout the 4 time points: 1) before the baseline ppTMS procedure; 2) before drug administration; 3) 30 minutes after drug administration; 4) before discharge from the session, during the session.

Outcome measures

Outcome data not reported

Adverse Events

L-Theanine

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	L-Theanine n=11 participants at risk Subject will receive 400mg single dose of L-theanine, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded.	Placebo n=11 participants at risk Subject will receive 400mg single dose of matching Placebo, by oral ingestion with water. The capsules are prepared and dispensed by hospital pharmacy, with the investigator and participant both blinded.
Nervous system disorders Syncope	9.1% 1/11 • Number of events 1 • 72 hours after administration of each drug condition (single dose of L-theanine or placebo).	9.1% 1/11 • Number of events 1 • 72 hours after administration of each drug condition (single dose of L-theanine or placebo).

Additional Information

Dr. Shiwen Yuan

Butler Hospital

Phone: 2025783000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place