Attention Deficit Hyperactivity DisorderEarly Phase 1NCT03533556
Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder
A Early Phase 1 study testing L-theanine, Caffeine and L-theanine-Caffeine Combination in people with Attention Deficit Hyperactivity Disorder, run by Texas Tech University at 1 site in United States.
Trial summary
L-theanine and caffeine are two natural constituents of tea. Both of these compounds are among the U.S. Food and Drug Administration's list of Generally Recognized as Safe (GRAS) substances. Read more about this study
- Who is it for?
- Ages 8 to 17 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- L-theanine, Caffeine and L-theanine-Caffeine Combination
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2018to 31 Aug 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 8 to 17 years
- Men only
- Healthy volunteers accepted
- Child
Who may be able to join
- Children and adolescents (age 8-17 years)
- Male
- Diagnosed with ADHD by a clinician (e.g. a psychiatrist or a pediatrician)
- Responded to stimulants (i.e. the symptoms of ADHD have improved in the past with a prescription of stimulants)
Who cannot join
- Gross impairment of vision or hearing that would prevent the participants from performing neuropsychological tasks
- Inability to read and follow written instructions
- WISC-V IQ score of \< 80
- Physical, neurological or concurrent psychiatric impairments (except ADHD) that could affect cognitive and motor functions
- Regular intake of medication that could alter visual, auditory, cognitive or motor functions (except stimulants)
- History of head injury that resulted in loss of consciousness / history of brain surgery
Show all 15Show fewer
- Intake of drugs containing caffeine, other phosphodiesterase inhibitors or adenosine receptor blockers within the past 3 months
- Intake of medications which are known to have pharmacological interactions with caffeine within the past 3 months
- Current / past diagnosis of tics or other forms of dyskinesia
- History of development of headache, drowsiness, anxiety, insomnia or nausea following intake of caffeine or caffeine containing beverages
- Current / past history of smoking and / or alcohol or drug abuse
- Absolute contraindications to undergo MRI
- Unwillingness or inability to entirely refrain from use of electronic devices during study visits
- Unwillingness or inability to refrain from intake of L-theanine and caffeine containing food or beverages within the 24 hours prior to each study visit
- Unwillingness or inability to follow written, on-screen and verbal instructions given by the study team
Trial locations and contacts
1 site in 1 country.
United States1 site
Texas Tech University - Department of Human Development and Family Studies
Lubbock, Texas, 79409
About this study
Official title: Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Male Children and Adolescents With Attention Deficit Hyperactivity Disorder: a proof-of- Concept fMRI Study.
L-theanine and caffeine are two natural constituents of tea. Both of these compounds are among the U.S. Food and Drug Administration's list of Generally Recognized as Safe (GRAS) substances. Results of several clinical trials the PI and his team has conducted are consistent with results of many others to indicate that oral intake of each of 2.5 mg/kg body weight of L-theanine and 2.0 mg/kg body weight of caffeine is associated with improved attention in adults. Furthermore, there is evidence to suggest that, when taken in combination, L-theanine and caffeine seem to have additive effects in improving attention in adults. However, the specific actions of these substances have not been examined in children and adolescents with attention deficit hyperactivity disorder (ADHD), who are characterized by impaired attention, hyperkinesia and impulsivity.
Therefore, the investigators plan to study the functional activity of brains (both at rest and when performing standard tasks designed to measure attention) in children diagnosed with ADHD using functional magnetic resonance imaging, after they consume either 2.5 mg/kg of L-theanine, 2.0 mg/kg of caffeine and their combination as compared to a placebo (water). Based on our previous findings, the investigators expect to observe improvements (speed of responding and accuracy) in standard tests of attention with intake of L-theanine, caffeine and their combination as compared to the placebo. The investigators also expect to observe decreased functional activity in brain regions that typically show increased activity during mind wandering with intake of L-theanine, caffeine and their combination.
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- L-theanine, Caffeine, L-theanine-Caffeine Combination, Placebo
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-theanineDietary supplement
Oral administration of 2.5 mg/kg body weight of L-theanine dissolved in 100 ml of water
CaffeineDietary supplement
Oral administration of 2.0 mg/kg body weight of caffeine dissolved in 100 ml of water
L-theanine-Caffeine CombinationDietary supplement
Oral administration of a combination of 2.5 mg/kg body weight of L-theanine and 2.0 mg/kg body weight of caffeine dissolved in 100 ml of water
PlaceboOther
Oral administration of 100 ml of water
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences of fMRI blood oxygen level dependent (BOLD) responses of the brain in response to Stop Signals of an SSRT recorded following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of functional magnetic resonance imaging reactivity of the whole brain, anterior and posterior nodes of the default mode network, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex in response to stop signals of a stop signal reaction time task following administration of each treatment will be compared with the placebo.
Measured: 45 minutes after the administration of each treatment / placebo
Differences of fMRI blood oxygen level dependent (BOLD) responses of the brain in a Go-NoGo CPT recorded following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of functional magnetic resonance imaging reactivity of the whole brain, anterior and posterior nodes of the default mode network, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex in Go-NoGo continuous performance task following administration of each treatment will be compared with the placebo.
Measured: 60 minutes after the administration of each treatment / placebo
Differences of resting state fMRI functional connectivity recorded following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of functional magnetic resonance imaging resting state functional connectivity of the anterior and posterior nodes of the default mode network, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex and the remaining regions of the brain following administration of each treatment will be compared with the placebo.
Measured: 75 minutes after the administration of each treatment / placebo
Secondary outcomes (9)
Differences of cerebral blood flow measured following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of cerebral blood flow estimated using arterial spin labeled echo following administration of each treatment will be compared with the placebo.
Measured: 80 minutes following administration of each treatment / placebo
Differences of delay discounting following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of delay discounting as measured using a delay discounting task presented on a laptop computer following administration of each treatment will be compared with the placebo.
Measured: 140 minutes following administration of each treatment / placebo
Differences of stop signal delay following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of stop signal delay of a stop signal reaction time task performed in the magnetic resonance imaging scanner following administration of each treatment will be compared with the placebo.
Measured: 45 minutes following administration of each treatment / placebo
Differences of reaction times of correct Go responses in a Go-NoGo CPT following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of reaction times of correct Go responses in a Go-NoGo continuous performance task performed in the magnetic resonance imaging scanner following administration of each treatment will be compared with the placebo.
Measured: 60 minutes following administration of each treatment / placebo
Differences of commission errors in the Go-NoGo CPT following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of commission errors in the Go-NoGo continuous performance task performed in the magnetic resonance imaging scanner following administration of each treatment will be compared with the placebo.
Measured: 60 minutes following administration of each treatment / placebo
Differences of performance in Flanker Inhibitory Control and Attention Test following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of performance in Flanker Inhibitory Control and Attention Test of the NIH Toolbox Cognition Battery following administration of each treatment will be compared with the placebo.
Measured: 100 minutes following administration of each treatment / placebo
Differences of performance in Dimensional Change Card Sort Test following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of performance in Dimensional Change Card Sort Test of the NIH Toolbox Cognition Battery following administration of each treatment will be compared with the placebo.
Measured: 100 minutes following administration of each treatment / placebo
Differences of performance in Pattern Comparison Processing Speed Test following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of performance in Pattern Comparison Processing Speed Test of the NIH Toolbox Cognition Battery following administration of each treatment will be compared with the placebo.
Measured: 100 minutes following administration of each treatment / placebo
Differences of post- vs. pre-treatment change of STAI-CH State Scale following administration of each treatment and the placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of State Trait Anxiety Inventory for Children (State Questionnaire) immediately prior to and following administration of each treatment will be compared with the corresponding post- vs. pre-treatment change of placebo.
Measured: Immediately before and 90 minutes after administration of each treatment / placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start14 May 2018
- Primary completion31 Aug 2018
- Study completion31 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Attention Deficit Hyperactivity DisorderStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 2.5 mg/kg body weight of L-theanine, 2.0 mg/kg body weight of caffeine and their combination each dissolved in 100 ml of water (solvent) or the solvent alone (i.e. placebo) will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Texas Tech University
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Tech University Health Sciences Center
- Responsible party
- Sponsor
- Investigators
- Chanaka Kahathuduwa, MBBS PhD, Principal investigator, Texas Tech University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03533556
- Sponsor's protocol ID
- IRB2017-767
- Status last verified
- Apr 2019
- First submitted
- 10 May 2018
- Last updated
- 12 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Male Children and Adolescents With Attention Deficit Hyperactivity Disorder: a proof-of- Concept fMRI Study.
- ClinicalTrials.gov ID
- NCT03533556
- Acronym / sponsor ID
- IRB2017-767
- Conditions
- Attention Deficit Hyperactivity Disorder
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Texas Tech UniversityUniversity, hospital or other
- Collaborators
- Texas Tech University Health Sciences Center
- Study start
- 14 May 2018 (actual)
- Primary completion
- 31 Aug 2018 (actual)
- Study completion
- 31 Aug 2018 (actual)
- First posted
- 23 May 2018 (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.
L-theanine and caffeine are two natural constituents of tea. Both of these compounds are among the U.S. Food and Drug Administration's list of Generally Recognized as Safe (GRAS) substances. Results of several clinical trials the PI and his team has conducted are consistent with results of many others to indicate that oral intake of each of 2.5 mg/kg body weight of L-theanine and 2.0 mg/kg body weight of caffeine is associated with improved attention in adults. Furthermore, there is evidence to suggest that, when taken in combination, L-theanine and caffeine seem to have additive effects in improving attention in adults. However, the specific actions of these substances have not been examined in children and adolescents with attention deficit hyperactivity disorder (ADHD), who are characterized by impaired attention, hyperkinesia and impulsivity.
Therefore, the investigators plan to study the functional activity of brains (both at rest and when performing standard tasks designed to measure attention) in children diagnosed with ADHD using functional magnetic resonance imaging, after they consume either 2.5 mg/kg of L-theanine, 2.0 mg/kg of caffeine and their combination as compared to a placebo (water). Based on our previous findings, the investigators expect to observe improvements (speed of responding and accuracy) in standard tests of attention with intake of L-theanine, caffeine and their combination as compared to the placebo. The investigators also expect to observe decreased functional activity in brain regions that typically show increased activity during mind wandering with intake of L-theanine, caffeine and their combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Model description
- 2.5 mg/kg body weight of L-theanine, 2.0 mg/kg body weight of caffeine and their combination each dissolved in 100 ml of water (solvent) or the solvent alone (i.e. placebo) will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order.
Who may qualify
- Ages
- 8 to 17 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Children and adolescents (age 8-17 years)
- Male
- Diagnosed with ADHD by a clinician (e.g. a psychiatrist or a pediatrician)
- Responded to stimulants (i.e. the symptoms of ADHD have improved in the past with a prescription of stimulants)
Key exclusion criteria (15 listed)
- Gross impairment of vision or hearing that would prevent the participants from performing neuropsychological tasks
- Inability to read and follow written instructions
- WISC-V IQ score of \< 80
- Physical, neurological or concurrent psychiatric impairments (except ADHD) that could affect cognitive and motor functions
- Regular intake of medication that could alter visual, auditory, cognitive or motor functions (except stimulants)
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 |
|---|---|---|
| L-theanineOral administration of 2.5 mg/kg body weight of L-theanine dissolved in 100 ml of water | Dietary supplement | – |
| CaffeineOral administration of 2.0 mg/kg body weight of caffeine dissolved in 100 ml of water | Dietary supplement | – |
| L-theanine-Caffeine CombinationOral administration of a combination of 2.5 mg/kg body weight of L-theanine and 2.0 mg/kg body weight of caffeine dissolved in 100 ml of water | Dietary supplement | – |
| PlaceboOral administration of 100 ml of water | Other | – |
Primary outcome
Differences of fMRI blood oxygen level dependent (BOLD) responses of the brain in response to Stop Signals of an SSRT recorded following administration of each treatment and the placebo
Time frame: 45 minutes after the administration of each treatment / placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of functional magnetic resonance imaging reactivity of the whole brain, anterior and posterior nodes of the default mode network, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex in response to stop signals of a stop signal reaction time task following administration of each treatment will be compared with the placebo.
Differences of fMRI blood oxygen level dependent (BOLD) responses of the brain in a Go-NoGo CPT recorded following administration of each treatment and the placebo
Time frame: 60 minutes after the administration of each treatment / placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of functional magnetic resonance imaging reactivity of the whole brain, anterior and posterior nodes of the default mode network, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex in Go-NoGo continuous performance task following administration of each treatment will be compared with the placebo.
Differences of resting state fMRI functional connectivity recorded following administration of each treatment and the placebo
Time frame: 75 minutes after the administration of each treatment / placebo
L-theanine, caffeine, L-theanine-caffeine combination and placebo will be administered on 4 separate days (at least 5 days apart) in a random counter-balanced order. Differences of functional magnetic resonance imaging resting state functional connectivity of the anterior and posterior nodes of the default mode network, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex and the remaining regions of the brain following administration of each treatment will be compared with the placebo.
9 secondary outcomes
Differences of cerebral blood flow measured following administration of each treatment and the placebo
Time frame: 80 minutes following administration of each treatment / placebo
Differences of delay discounting following administration of each treatment and the placebo
Time frame: 140 minutes following administration of each treatment / placebo
Differences of stop signal delay following administration of each treatment and the placebo
Time frame: 45 minutes following administration of each treatment / placebo
Differences of reaction times of correct Go responses in a Go-NoGo CPT following administration of each treatment and the placebo
Time frame: 60 minutes following administration of each treatment / placebo
Differences of commission errors in the Go-NoGo CPT following administration of each treatment and the placebo
Time frame: 60 minutes following administration of each treatment / placebo
Differences of performance in Flanker Inhibitory Control and Attention Test following administration of each treatment and the placebo
Time frame: 100 minutes following administration of each treatment / placebo
Differences of performance in Dimensional Change Card Sort Test following administration of each treatment and the placebo
Time frame: 100 minutes following administration of each treatment / placebo
Differences of performance in Pattern Comparison Processing Speed Test following administration of each treatment and the placebo
Time frame: 100 minutes following administration of each treatment / placebo
Differences of post- vs. pre-treatment change of STAI-CH State Scale following administration of each treatment and the placebo
Time frame: Immediately before and 90 minutes after administration of each treatment / placebo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
- Individual participant dataSharing planned: Undecided
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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.
Chanaka Kahathuduwa, MBBS PhD principal investigator
Texas Tech University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing L-theanine, Caffeine and L-theanine-Caffeine Combination in people with Attention Deficit Hyperactivity Disorder, run by Texas Tech University at 1 site in United States.
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 4 inclusion and 15 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: finished, as of the sponsor's last update on 12 Apr 2019. 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 United States. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Differences of fMRI blood oxygen level dependent (BOLD) responses of the brain in response to Stop Signals of an SSRT recorded following administration of each treatment and the placebo (time frame: 45 minutes after the administration of each treatment / placebo). The study lists 3 primary outcomes in all. 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 12 Apr 2019.