Clinical trial NCT03533556: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Attention Deficit Hyperactivity Disorder
Lead sponsor: Texas Tech University
Sponsor class: OTHER
Collaborators: name: Texas Tech University Health Sciences Center
First posted: 2018-05-23
Enrollment: 6
Sex: MALE
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Children and adolescents (age 8-17 years)
2. Male
3. Diagnosed with ADHD by a clinician (e.g. a psychiatrist or a pediatrician)
4. Responded to stimulants (i.e. the symptoms of ADHD have improved in the past with a prescription of stimulants)

Exclusion Criteria:

1. Gross impairment of vision or hearing that would prevent the participants from performing neuropsychological tasks
2. Inability to read and follow written instructions
3. WISC-V IQ score of \&lt; 80
4. Physical, neurological or concurrent psychiatric impairments (except ADHD) that could affect cognitive and motor functions
5. Regular intake of medication that could alter visual, auditory, cognitive or motor functions (except stimulants)
6. History of head injury that resulted in loss of consciousness / history of brain surgery
7. Intake of drugs containing caffeine, other phosphodiesterase inhibitors or adenosine receptor blockers within the past 3 months
8. Intake of medications which are known to have pharmacological interactions with caffeine within the past 3 months
9. Current / past diagnosis of tics or other forms of dyskinesia
10. History of development of headache, drowsiness, anxiety, insomnia or nausea following intake of caffeine or caffeine containing beverages
11. Current / past history of smoking and / or alcohol or drug abuse
12. Absolute contraindications to undergo MRI
13. Unwillingness or inability to entirely refrain from use of electronic devices during study visits
14. 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
15. Unwillingness or inability to follow written, on-screen and verbal instructions given by the study team

Primary outcomes:
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
timeFrame: 45 minutes after the administration of each treatment / placebo
measure: 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
timeFrame: 60 minutes after the administration of each treatment / placebo
measure: Differences of resting state fMRI functional connectivity recorded following administration of each treatment and the placebo
timeFrame: 75 minutes after the administration of each treatment / placebo
Secondary outcomes:
measure: Differences of cerebral blood flow measured following administration of each treatment and the placebo
timeFrame: 80 minutes following administration of each treatment / placebo
measure: Differences of delay discounting following administration of each treatment and the placebo
timeFrame: 140 minutes following administration of each treatment / placebo
measure: Differences of stop signal delay following administration of each treatment and the placebo
timeFrame: 45 minutes following administration of each treatment / placebo
measure: Differences of reaction times of correct Go responses in a Go-NoGo CPT following administration of each treatment and the placebo
timeFrame: 60 minutes following administration of each treatment / placebo
measure: Differences of commission errors in the Go-NoGo CPT following administration of each treatment and the placebo
timeFrame: 60 minutes following administration of each treatment / placebo
measure: Differences of performance in Flanker Inhibitory Control and Attention Test following administration of each treatment and the placebo
timeFrame: 100 minutes following administration of each treatment / placebo
measure: Differences of performance in Dimensional Change Card Sort Test following administration of each treatment and the placebo
timeFrame: 100 minutes following administration of each treatment / placebo
measure: Differences of performance in Pattern Comparison Processing Speed Test following administration of each treatment and the placebo
timeFrame: 100 minutes following administration of each treatment / placebo
measure: Differences of post- vs. pre-treatment change of STAI-CH State Scale following administration of each treatment and the placebo
timeFrame: Immediately before and 90 minutes after administration of each treatment / placebo
Other outcomes:
measure: Differences of commission errors in SSRT following administration of each treatment and the placebo
timeFrame: 45 minutes following administration of each treatment / placebo
measure: Differences of omission errors in SSRT following administration of each treatment and the placebo
timeFrame: 45 minutes following administration of each treatment / placebo
measure: Differences of omission errors in Go-NoGo CPT following administration of each treatment and the placebo
timeFrame: 60 minutes following administration of each treatment / placebo
measure: Differences of performance in Picture Sequence Memory Test following administration of each treatment and the placebo
timeFrame: 100 minutes following administration of each treatment / placebo
measure: Differences of performance in List Sorting Working Memory Test following administration of each treatment and the placebo
timeFrame: 100 minutes following administration of each treatment / placebo
Locations:
city: Lubbock
country: United States
facility: Texas Tech University - Department of Human Development and Family Studies
state: Texas
Study officials:
affiliation: Texas Tech University
name: Chanaka Kahathuduwa, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: