Back to resultsEffects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder
Primary Purpose
Attention Deficit Hyperactivity Disorder
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
L-theanine
Caffeine
L-theanine-Caffeine Combination
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Attention Deficit Hyperactivity Disorder
Eligibility Criteria
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
Sites / Locations
- Texas Tech University - Department of Human Development and Family Studies
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03533556
First Posted
May 10, 2018
Last Updated
April 10, 2019
Sponsor
Texas Tech University
Collaborators
Texas Tech University Health Sciences Center
1. Study Identification
Unique Protocol Identification Number
NCT03533556
Brief Title
Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder
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.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
May 14, 2018 (Actual)
Primary Completion Date
August 31, 2018 (Actual)
Study Completion Date
August 31, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Texas Tech University
Collaborators
Texas Tech University Health Sciences Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Hyperactivity Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
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
Participant
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Dietary Supplement
Intervention Name(s)
L-theanine
Intervention Description
Oral administration of 2.5 mg/kg body weight of L-theanine dissolved in 100 ml of water
Intervention Type
Dietary Supplement
Intervention Name(s)
Caffeine
Intervention Description
Oral administration of 2.0 mg/kg body weight of caffeine dissolved in 100 ml of water
Intervention Type
Dietary Supplement
Intervention Name(s)
L-theanine-Caffeine Combination
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Oral administration of 100 ml of water
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
45 minutes after the administration of each treatment / placebo
Title
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
Description
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.
Time Frame
60 minutes after the administration of each treatment / placebo
Title
Differences of resting state fMRI functional connectivity recorded following administration of each treatment and the placebo
Description
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.
Time Frame
75 minutes after the administration of each treatment / placebo
Secondary Outcome Measure Information:
Title
Differences of cerebral blood flow measured following administration of each treatment and the placebo
Description
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.
Time Frame
80 minutes following administration of each treatment / placebo
Title
Differences of delay discounting following administration of each treatment and the placebo
Description
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.
Time Frame
140 minutes following administration of each treatment / placebo
Title
Differences of stop signal delay following administration of each treatment and the placebo
Description
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.
Time Frame
45 minutes following administration of each treatment / placebo
Title
Differences of reaction times of correct Go responses in a Go-NoGo CPT following administration of each treatment and the placebo
Description
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.
Time Frame
60 minutes following administration of each treatment / placebo
Title
Differences of commission errors in the Go-NoGo CPT following administration of each treatment and the placebo
Description
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.
Time Frame
60 minutes following administration of each treatment / placebo
Title
Differences of performance in Flanker Inhibitory Control and Attention Test following administration of each treatment and the placebo
Description
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.
Time Frame
100 minutes following administration of each treatment / placebo
Title
Differences of performance in Dimensional Change Card Sort Test following administration of each treatment and the placebo
Description
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.
Time Frame
100 minutes following administration of each treatment / placebo
Title
Differences of performance in Pattern Comparison Processing Speed Test following administration of each treatment and the placebo
Description
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.
Time Frame
100 minutes following administration of each treatment / placebo
Title
Differences of post- vs. pre-treatment change of STAI-CH State Scale following administration of each treatment and the placebo
Description
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.
Time Frame
Immediately before and 90 minutes after administration of each treatment / placebo
Other Pre-specified Outcome Measures:
Title
Differences of commission errors in SSRT following administration of each treatment and the placebo
Description
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.
Time Frame
45 minutes following administration of each treatment / placebo
Title
Differences of omission errors in SSRT following administration of each treatment and the placebo
Description
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.
Time Frame
45 minutes following administration of each treatment / placebo
Title
Differences of omission errors in Go-NoGo CPT following administration of each treatment and the placebo
Description
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.
Time Frame
60 minutes following administration of each treatment / placebo
Title
Differences of performance in Picture Sequence Memory Test following administration of each treatment and the placebo
Description
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.
Time Frame
100 minutes following administration of each treatment / placebo
Title
Differences of performance in List Sorting Working Memory Test following administration of each treatment and the placebo
Description
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.
Time Frame
100 minutes following administration of each treatment / placebo
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Participant eligibility is based on self-representation of gender identity
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chanaka Kahathuduwa, MBBS PhD
Organizational Affiliation
Texas Tech University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas Tech University - Department of Human Development and Family Studies
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79409
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder
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