Effects of L-theanine and Caffeine on Attention and Attention-related Brain Activity of Children With Attention Deficit Hyperactivity Disorder

NCT03533556 | Completed Early Phase 1

• 1 other identifier: IRB2017-767
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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

  80 minutes following administration of each treatment / placebo

• Differences of delay discounting following administration of each treatment and the placebo

  140 minutes following administration of each treatment / placebo

• Differences of stop signal delay following administration of each treatment and 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

  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

  60 minutes following administration of each treatment / placebo

Other Outcomes (5)

• Differences of commission errors in SSRT following administration of each treatment and the placebo

  45 minutes following administration of each treatment / placebo

• Differences of omission errors in SSRT following administration of each treatment and 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

  60 minutes following administration of each treatment / placebo

Interventions

L-theanine DIETARY_SUPPLEMENT

Oral administration of 2.5 mg/kg body weight of L-theanine dissolved in 100 ml of water

Caffeine DIETARY_SUPPLEMENT

Oral administration of 2.0 mg/kg body weight of caffeine dissolved in 100 ml of water

L-theanine-Caffeine Combination DIETARY_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

Placebo OTHER

Oral administration of 100 ml of water

Eligibility Criteria

• Age: 8 Years - 17 Years
• Gender Eligibility Details: Participant eligibility is based on self-representation of gender identity
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Texas Tech University: lead
• Texas Tech University Health Sciences Center: collaborator

Study Sites (1)

Texas Tech University - Department of Human Development and Family Studies

Lubbock, Texas, 79409, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

theanine; Caffeine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Chanaka Kahathuduwa, MBBS PhD

  Texas Tech University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 23, 2018
• Study Start: May 14, 2018
• Primary Completion: August 31, 2018
• Study Completion: August 31, 2018
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

US (1)