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Effects of USP Methylene Blue on Cognitive and fMRI Brain Activity

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ClinicalTrials.gov Identifier: NCT01836094
Recruitment Status : Completed
First Posted : April 19, 2013
Last Update Posted : April 11, 2017
Sponsor:
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Brief 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.


Condition or disease Intervention/treatment Phase
Brain Activity Drug: Methylene Blue (USP grade, 280mg oral) Drug: Placebo Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Beneficial Effects of Methylene Blue on Human Cognitive and fMRI Measures
Study Start Date : August 2013
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Methylene Blue
Methylene Blue, 280mg, oral, one time
Drug: Methylene Blue (USP grade, 280mg oral)
Other Name: USP Methylene Blue, Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate

Placebo Comparator: Placebo
FD&C Blue No. 2 (food dye), oral, one time
Drug: Placebo
oral, one time
Other Name: FD&C Blue No. 2 (food dye)




Primary Outcome Measures :
  1. Improvement in reaction time assessed by fMRI measurements and PVT measurements [ Time Frame: 1 hour ]
    fMRI will be assessed using standard fMRI analysis tools. Psychomotor-Vigilance-Test (PVT) measurements will be made using a computer program written in Psychology Experiment Building Language (PBL).

  2. Improvement in memory assessed by fMRI measurements and DMS measurements [ Time Frame: 1 hour ]
    fMRI will be assessed using standard fMRI analysis tools. Delayed-match-to-sample task (DMS) measurements will be made using a computer program written in Psychology Experiment Building Language (PBL).


Secondary Outcome Measures :
  1. Enhanced fMRI responses to visual-motor task [ Time Frame: 1-2 hours ]
    fMRI will be assessed using standard fMRI analysis tools.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 - 65 years, self declared healthy individuals
  • English speaker and be able to give consent

Exclusion Criteria:

  • Contraindication for MRI (pacemaker, metal implants, etc.)
  • Claustrophobia
  • Pregnant (child-bearing age females will be tested to exclude pregnancy onsite)
  • Breast-feeding
  • A history of hypersensitivity or allergy to methylene blue, glucose-6-phosphate dehydrogenase deficiency (determined via questionnaire)
  • Neurological, mental, or cardiovascular disorders
  • Liver, kidney disorders, kidney or liver transplant, hypertension, diabetes, etc.
  • Known hypersensitivity to thiazide diuretics and phenothiazines
  • A history of a psychotic disorder or panic disorder, violent or suicidal behavior, psychiatric institutionalization or imprisonment
  • Any other condition, which in the opinion of the investigator, would put the participant at risk and warrant exclusion from the study
  • Methemoglobinemia
  • On any psychiatric serotonergic antidepressant medication or drugs of abuse currently or within the last 5 weeks
  • History of panic attack
  • Color Blindness

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01836094


Locations
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United States, Texas
Research Imaging Institute, The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Investigators
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Principal Investigator: Timothy Q. Duong, Ph.D. The University of Texas Health Science Center at San Antonio

Publications:
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Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01836094    
Other Study ID Numbers: NS 13-208
First Posted: April 19, 2013    Key Record Dates
Last Update Posted: April 11, 2017
Last Verified: April 2017
Keywords provided by The University of Texas Health Science Center at San Antonio:
Methylene Blue
Memory
Mental Fatigue
Brain metabolism
fMRI
psychomotor vigilance task (PVT)
delayed match-to-sample memory task
PVT
DMS
Additional relevant MeSH terms:
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Methylene Blue
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action