Brain ActivityEarly Phase 1NCT01836094
Effects of USP Methylene Blue on Cognitive and fMRI Brain Activity
A Early Phase 1 study testing Methylene Blue (USP grade, 280mg oral) in people with Brain Activity, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Activity
- What is being tested?
- Methylene Blue (USP grade, 280mg oral)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Mar 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 - 65 years, self declared healthy individuals
- English speaker and be able to give consent
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Research Imaging Institute, The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: Beneficial Effects of Methylene Blue on Human Cognitive and fMRI Measures
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.
Read the 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.
- Conditions
- Brain Activity
- Being tested
- Methylene Blue (USP grade, 280mg oral), Placebo
- Keywords
- Methylene Blue, Memory, Mental Fatigue, Brain metabolism, fMRI, psychomotor vigilance task (PVT), delayed match-to-sample memory task, PVT, DMS
- Medical subject headings
- Mental Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene Blue (USP grade, 280mg oral)Drug
Also called USP Methylene Blue, Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate
PlaceboDrug
Also called FD&C Blue No. 2 (food dye)
oral, one time
| Study group | Role | What they receive |
|---|---|---|
| Methylene Blue | Experimental | Methylene Blue, 280mg, oral, one time Receives: Drug: Methylene Blue (USP grade, 280mg oral) |
| Placebo | Placebo comparator | FD\&C Blue No. 2 (food dye), oral, one time Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in reaction time assessed by fMRI measurements and PVT measurements
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).
Measured: 1 hour
Improvement in memory assessed by fMRI measurements and DMS measurements
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).
Measured: 1 hour
Secondary outcomes (1)
Enhanced fMRI responses to visual-motor task
fMRI will be assessed using standard fMRI analysis tools.
Measured: 1-2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2013 (estimated)
- Study startAug 2013
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Brain ActivityStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy Q. Duong, Ph.D., Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01836094
- Sponsor's protocol ID
- NS 13-208
- Status last verified
- Apr 2017
- First submitted
- 12 Apr 2013
- Last updated
- 11 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Riha PD, Bruchey AK, Echevarria DJ, Gonzalez-Lima F. Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption. Eur J Pharmacol. 2005 Mar 28;511(2-3):151-8. doi: 10.1016/j.ejphar.2005.02.001.
PubMed 15792783Gonzalez-Lima F, Bruchey AK. Extinction memory improvement by the metabolic enhancer methylene blue. Learn Mem. 2004 Sep-Oct;11(5):633-40. doi: 10.1101/lm.82404.
PubMed 15466319Wrubel KM, Riha PD, Maldonado MA, McCollum D, Gonzalez-Lima F. The brain metabolic enhancer methylene blue improves discrimination learning in rats. Pharmacol Biochem Behav. 2007 Apr;86(4):712-7. doi: 10.1016/j.pbb.2007.02.018. Epub 2007 Mar 6.
PubMed 17428524Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA, Goldberg MS, She H, Mao Z, Simpkins JW, Yang SH. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem. 2011 May 6;286(18):16504-15. doi: 10.1074/jbc.M110.208447. Epub 2011 Mar 18.
PubMed 21454572Lim J, Wu WC, Wang J, Detre JA, Dinges DF, Rao H. Imaging brain fatigue from sustained mental workload: an ASL perfusion study of the time-on-task effect. Neuroimage. 2010 Feb 15;49(4):3426-35. doi: 10.1016/j.neuroimage.2009.11.020. Epub 2009 Nov 24.
PubMed 19925871Bruchey AK, Gonzalez-Lima F. Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue. Am J Pharmacol Toxicol. 2008 Jan 1;3(1):72-79. doi: 10.3844/ajptsp.2008.72.79.
PubMed 20463863
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beneficial Effects of Methylene Blue on Human Cognitive and fMRI Measures
- ClinicalTrials.gov ID
- NCT01836094
- Acronym / sponsor ID
- NS 13-208
- Conditions
- Brain Activity
- Keywords
- Methylene Blue, Memory, Mental Fatigue, Brain metabolism, fMRI, psychomotor vigilance task (PVT), delayed match-to-sample memory task, PVT
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 19 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylene Blue | Experimental | Drug: Methylene Blue (USP grade, 280mg oral)Methylene Blue, 280mg, oral, one time |
| Placebo | Placebo comparator | Drug: PlaceboFD\&C Blue No. 2 (food dye), oral, one time |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18 - 65 years, self declared healthy individuals
- English speaker and be able to give consent
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylene Blue (USP grade, 280mg oral)Also: USP Methylene Blue, Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate | Drug | Methylene Blue |
| PlaceboAlso: FD&C Blue No. 2 (food dye)oral, one time | Drug | Placebo |
Primary outcome
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).
1 secondary outcome
Enhanced fMRI responses to visual-motor task
Time frame: 1-2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2017.
- Background: PubMed 15792783Riha PD, Bruchey AK, Echevarria DJ, Gonzalez-Lima F. Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption. Eur J Pharmacol. 2005 Mar 28;511(2-3):151-8. doi: 10.1016/j.ejphar.2005.02.001.
- Background: PubMed 15466319Gonzalez-Lima F, Bruchey AK. Extinction memory improvement by the metabolic enhancer methylene blue. Learn Mem. 2004 Sep-Oct;11(5):633-40. doi: 10.1101/lm.82404.
- Background: PubMed 17428524Wrubel KM, Riha PD, Maldonado MA, McCollum D, Gonzalez-Lima F. The brain metabolic enhancer methylene blue improves discrimination learning in rats. Pharmacol Biochem Behav. 2007 Apr;86(4):712-7. doi: 10.1016/j.pbb.2007.02.018. Epub 2007 Mar 6.
- Background: PubMed 21454572Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA, Goldberg MS, She H, Mao Z, Simpkins JW, Yang SH. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem. 2011 May 6;286(18):16504-15. doi: 10.1074/jbc.M110.208447. Epub 2011 Mar 18.
- Background: PubMed 19925871Lim J, Wu WC, Wang J, Detre JA, Dinges DF, Rao H. Imaging brain fatigue from sustained mental workload: an ASL perfusion study of the time-on-task effect. Neuroimage. 2010 Feb 15;49(4):3426-35. doi: 10.1016/j.neuroimage.2009.11.020. Epub 2009 Nov 24.
- Background: PubMed 20463863Bruchey AK, Gonzalez-Lima F. Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue. Am J Pharmacol Toxicol. 2008 Jan 1;3(1):72-79. doi: 10.3844/ajptsp.2008.72.79.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy Q. Duong, Ph.D. principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Methylene Blue (USP grade, 280mg oral) in people with Brain Activity, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in reaction time assessed by fMRI measurements and PVT measurements (time frame: 1 hour). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01836094, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2017.