Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of USP Methylene Blue on Cognitive and fMRI Brain Activity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE April 12, 2013
First Posted Date  ICMJE April 19, 2013
Last Update Posted Date April 11, 2017
Study Start Date  ICMJE August 2013
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2013)
  • 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).
  • 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2013)
Enhanced fMRI responses to visual-motor task [ Time Frame: 1-2 hours ]
fMRI will be assessed using standard fMRI analysis tools.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of USP Methylene Blue on Cognitive and fMRI Brain Activity
Official Title  ICMJE Beneficial Effects of Methylene Blue on Human Cognitive and fMRI Measures
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Brain Activity
Intervention  ICMJE
  • Drug: Methylene Blue (USP grade, 280mg oral)
    Other Name: USP Methylene Blue, Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate
  • Drug: Placebo
    oral, one time
    Other Name: FD&C Blue No. 2 (food dye)
Study Arms  ICMJE
  • Experimental: Methylene Blue
    Methylene Blue, 280mg, oral, one time
    Intervention: Drug: Methylene Blue (USP grade, 280mg oral)
  • Placebo Comparator: Placebo
    FD&C Blue No. 2 (food dye), oral, one time
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2016)
36
Original Estimated Enrollment  ICMJE
 (submitted: April 18, 2013)
50
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01836094
Other Study ID Numbers  ICMJE NS 13-208
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The University of Texas Health Science Center at San Antonio
Study Sponsor  ICMJE The University of Texas Health Science Center at San Antonio
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Timothy Q. Duong, Ph.D. The University of Texas Health Science Center at San Antonio
PRS Account The University of Texas Health Science Center at San Antonio
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP