- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03533556
Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder
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.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Lubbock, Texas, United States, 79409
- Texas Tech University - Department of Human Development and Family Studies
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
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.
|
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
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.
|
75 minutes after the administration of each treatment / placebo
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Differences of cerebral blood flow measured following administration of each treatment and the placebo
Time Frame: 80 minutes following 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 cerebral blood flow estimated using arterial spin labeled echo following administration of each treatment will be compared with the placebo.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
Immediately before and 90 minutes after administration of each treatment / placebo
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Differences of commission errors in SSRT following administration of each treatment and the placebo
Time Frame: 45 minutes following 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 commission errors of the stop signal reaction time task performed in the magnetic resonance imaging scanner following administration of each treatment will be compared with the placebo.
|
45 minutes following administration of each treatment / placebo
|
Differences of omission errors in SSRT following administration of each treatment and the placebo
Time Frame: 45 minutes following 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 omission errors of the stop signal reaction time task performed in the magnetic resonance imaging scanner following administration of each treatment will be compared with the placebo.
|
45 minutes following administration of each treatment / placebo
|
Differences of omission errors in Go-NoGo CPT following administration of each treatment and the placebo
Time Frame: 60 minutes following 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 omission errors of the Go-NoGo continuous performance task performed in the magnetic resonance imaging scanner following administration of each treatment will be compared with the placebo.
|
60 minutes following administration of each treatment / placebo
|
Differences of performance in Picture Sequence Memory Test following administration of each treatment and the placebo
Time Frame: 100 minutes following 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 performance in Picture Sequence Memory Test of the NIH Toolbox Cognition Battery following administration of each treatment will be compared with the placebo.
|
100 minutes following administration of each treatment / placebo
|
Differences of performance in List Sorting Working Memory Test following administration of each treatment and the placebo
Time Frame: 100 minutes following 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 performance in List Sorting Working Memory Test of the NIH Toolbox Cognition Battery following administration of each treatment will be compared with the placebo.
|
100 minutes following administration of each treatment / placebo
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Chanaka Kahathuduwa, MBBS PhD, Texas Tech University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Neurologic Manifestations
- Dyskinesias
- Attention Deficit and Disruptive Behavior Disorders
- Neurodevelopmental Disorders
- Attention Deficit Disorder with Hyperactivity
- Hyperkinesis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Purinergic Antagonists
- Purinergic Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Caffeine
Other Study ID Numbers
- IRB2017-767
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Attention Deficit Hyperactivity Disorder
-
Cingulate TherapeuticsRecruitingPhase 3 Efficacy and Safety Laboratory Classroom Study in Pediatrics (6-12) With ADHD Using CTx-1301ADHD | Attention Deficit Hyperactivity Disorder | Attention Deficit Disorder With Hyperactivity | ADHD - Combined Type | Attention Deficit Hyperactivity Disorder Combined | Attention Deficit Hyper Activity | Attention-deficit HyperactivityUnited States
-
Ornit CohenUnknownAttention Deficit Hyperactivity Disorder | Attention Deficit Disorder With Hyperactivity | Attention Deficit Disorder | Attention Deficit Disorders With Hyperactivity | Attention Deficit Hyperactivity DisordersIsrael
-
Cingulate TherapeuticsPremier Research Group plcActive, not recruitingADHD | Attention Deficit Hyperactivity Disorder | ADHD - Combined Type | Attention Deficit Hyperactivity Disorder Combined | Attention Deficit Hyper Activity | Attention-deficit HyperactivityUnited States
-
Children's National Research InstituteRecruitingADHD | Attention Deficit Hyperactivity Disorder | Attention-Deficit Hyperactivity Disorder | Attention Deficit Disorder | ADD | ADHD Predominantly Inattentive Type | ADHD - Combined Type | ADHD, Predominantly Hyperactive - Impulsive | Attention-Deficit Disorder in Adolescence | Attention-Deficit Hyperactivity...United States
-
Fondation LenvalCompletedAttention Deficit Disorder With Hyperactivity | Attention Deficit Disorder Without HyperactivityFrance
-
University Hospital Bispebjerg and FrederiksbergMental Health Services in the Capital Region, DenmarkRecruitingSleep Disturbance | Neurodevelopmental Disorders | Attention Deficit Hyperactivity Disorder | Attention Deficit Disorder | Attention-Deficit Hyperactivity Disorder, Unspecified Type | Attention-deficit Hyperactivity | Hyperkinetic Conduct DisorderDenmark
-
Corium, Inc.Worldwide Clinical Trials; Premier Research Group plc; Almac; Prometrika, LLCRecruitingAttention Deficit/Hyperactivity DisorderUnited States
-
Corium, Inc.Premier Research Group plc; Almac; Prometrika, LLCRecruitingAttention Deficit/Hyperactivity DisorderUnited States
-
Massachusetts General HospitalShire Human Genetic Therapies, Inc.Active, not recruitingAttention Deficit/Hyperactivity DisorderUnited States
-
Ataturk UniversityCompletedAttention-deficit/Hyperactivity DisorderTurkey
Clinical Trials on L-theanine
-
Sha'ar Menashe Mental Health CenterStanley Medical Research Institute; Beersheva Mental Health CenterCompleted
-
Butler HospitalCompletedPsychiatric Disorder | Cortical ExcitabilityUnited States
-
The University of Texas Health Science Center,...CompletedTheanine, (L)-IsomerUnited States
-
Ethical Naturals, Inc.KGK Science Inc.Active, not recruiting
-
University of British ColumbiaCompleted
-
Northumbria UniversityCompletedCognitive Function | MoodUnited Kingdom
-
Sha'ar Menashe Mental Health CenterTirat Carmel Mental Health CenterUnknownSchizophrenia | Schizoaffective Disorder
-
University of ShizuokaCompletedHealthy StudentsJapan
-
University of FloridaRecruitingMotor Activity | Cognitive Symptom | Stress Response | Mental Stress | Physiological Stress | Multitasking BehaviorUnited States
-
Ocean Spray Cranberries, Inc.Atlantia Food Clinical TrialsCompletedMood | AttentionUnited States