Effects of USP Methylene Blue on Cognitive and fMRI Brain Activity
Condition: Brain Activity
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The purpose of the study is to evaluate whether low-dose USP methylene blue (MB) will: i)
      improve short-term memory retention in a delayed match-to-sample task, ii) reduce reaction
      time in a psychomotor vigilance test, and iii) enhance responses to a visual-motor task as
      measured by functional magnetic resonance imaging (fMRI).

      A single low-dose MB or placebo will be orally administered to self-declared healthy adults
      using double-blind study design. Non-invasive fMRI data will be acquired before and after MB
      administration in the same subjects. Each study will take 2-3 hours, inclusive of an hour
      break in between.
    

Detailed description: 
      Self-declared healthy adult volunteers will be studied using a double-blind,
      placebo-controlled design. After informed consent and familiarity with the tasks and the MRI
      environment, the subject will enter an MRI scanner and perform the following 3 tasks:

      Delayed match-to-sample task: The subject views an object for a few seconds. After a few
      (variable) seconds, the subject is presented with two patterns and the subject needs to press
      the left or right button based on whether the picture on the left or the right is the same as
      the previous picture. The correct and incorrect answers are recorded. A few of these trials
      will be cycled, lasting about 5-10 mins.

      Psychomotor vigilance test: The subject will receive a visual cue to press a button as fast
      as possible. The reaction time is recorded. A false start is when the subject presses before
      the visual cue and that trial is not counted. The subject is instructed to avoid a false
      start. A few of these trials will be cycled, lasting about 5-10 mins.

      Visual-motor task: The subject is instructed to tap his/her 4 fingers against the thumb every
      second and cycle through the 4 fingers, in synchrony with an alternating visual checkerboard
      patterns. A few of these trials will be cycled, lasting about 5-10 mins.

      For calibration of the fMRI signal, fMRI data will also be acquired during a brief (3-5 mins)
      inhalation of 5% CO2 in air.

      fMRI measurements will be made before intervention. The subject comes out of the scanner,
      orally ingests the USP MB or placebo, and waits for an hour (break). The same measurements
      will then be repeated.

      fMRI data acquisition: The MRI pulse sequences include standard and non-invasive anatomical
      MRI for co-registration, blood flow and blood-oxygen-level dependent (BOLD) fMRI. fMRI will
      image changes in regional brain activity associated with these tasks.

      In addition, one week after the fMRI study, the subject will be emailed a short questionnaire
      (which takes a few minutes to answer) and the responses can be returned via email.

      Data analysis: Standard fMRI analysis will be analyzed using established fMRI software.
      Statistical parametric analysis will be performed to generate activation maps. Task-evoked
      changes in brain activities will be analyzed and contrasted between placebo and MB conditions
      in the same subjects. Paired t-test will be used for group comparison with P < 0.05 (with
      bonferroni correction) considered statistically significant.

      Expected results: The investigators predict that, compared to placebo, MB will: i) improve
      short-term memory retention in a delayed match-to-sample task by memory performance and
      enhanced fMRI responses in the prefrontal cortex-hippocampus, ii) reduce reaction time in a
      psychomotor vigilance test and enhanced fMRI responses within a cortical sustained attention
      network and the motor systems, and iii) enhance responses in the visual and motor cortices.

      Power analysis: Sample sizes were calculated for a power of 80%, alpha = 0.05 to detect
      statistical difference between MB and placebo. The investigators estimate they will need 40
      subjects (complete studies) and thus will recruit 50 subjects to account for potential failed
      studies.
    

Intervention name(s): Methylene Blue (USP grade, 280mg oral); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): oral, one time
Other intervention name(s): USP Methylene Blue, Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate; FD&C Blue No. 2 (food dye)
Intervention MeSH terms: Methylene Blue
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Methylene Blue; Memory; Mental Fatigue; Brain metabolism; fMRI; psychomotor vigilance task (PVT); delayed match-to-sample memory task; PVT; DMS