Ignite Creation Date:
2024-05-06 @ 3:49 AM
Last Modification Date:
2024-10-26 @ 11:39 AM
Study NCT ID:
NCT02380573
Status:
COMPLETED
Last Update Posted:
2022-08-26
First Post:
2015-02-24
Brief Title:
Effects of Methylene Blue in Healthy Aging Mild Cognitive Impairment and Alzheimers Disease
Sponsor:
The University of Texas Health Science Center at San Antonio
Organization:
The University of Texas Health Science Center at San Antonio
Study Overview
Official Title:
Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging Mild Cognitive Impairment and Alzheimers Disease
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MB2
Brief Summary:
A double-blind placebo-controlled study that aims to investigate the effect of 2-week and 12-week administration of USP methylene blue MB on cerebral blood flow functional connectivity memory and attention cognitive abilities using fMRI and behavioral measures in healthy aging mild cognitive impairment MCI and mild Alzheimers disease AD subjects
Detailed Description:
Healthy aging and aging human subjects with mild cognitive impairment and mild Alzheimers disease from the TARCC cohort and South Texas 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 6 tasks
fMRI and behavioral data will be collected simultaneously while inside the scanner
Delayed match-to-sample task The subject views a pattern for a few seconds and then is prompted to recall the memorized pattern using a response system approx 10 mins
Face-name task The subject is shown blocks of stimuli where a novel or familiar face is paired with a name In a later run the subjects are asked whether the correct name is matched with the correct face approx 10 mins
Psychomotor vigilance task The subject receives a visual cue that alerts them to press a button as fast as possible approx 10 mins
Cerebral Blood Flow and Resting State fMRI Subject scanned with eyes closed and told to not think about a particular topic each lasting about 10 minutes
fMRI data acquisition fMRI and neuropsychological battery measurements will be made before the intervention These measurements will then be repeated after 2 weeks and 12 weeks
fMRI will image changes in regional brain activity associated with these tasks The MRI pulse sequences include diffusion tensor imaging standard and non-invasive anatomical and quantitative MRI for coregistration and blood-oxygen-level dependent BOLD fMRI
CO2 challenge Cerebral blood flow measurements will be obtained while the subject rests in the scanner after administration of medical-grade 5 CO2 in air for 3-5 minutes This will be repeated on weeks 2 and 12
Data analysis Standard fMRI analysis will be analyzed using established fMRI software Statistical parametric analysis will be performed to generate activation maps fMRI data will be corrected for multiple comparisons using a false discovery rate q 005 and threshold for cluster values to conservatively control for type I error Behavioral data will be analyzed with paired t-test and ANOVA calculations used for group comparison with p 005 with Bonferroni correction considered statistically significant
Expected results The investigators predict that compared to placebo MB will i improve working memory retention in a delayed match-to-sample task by memory performance and enhanced fMRI responses in the prefrontal cortex and parietal lobes ii improve episodic memory as determined by fMRI activation in the hippocampus medial temporal lobes and prefrontal cortex iii reduce reaction time in a psychomotor vigilance test and enhance fMRI responses within a cortical sustained attention network iv improve CBF and v improve fMRI connectivity in default mode and visuospatial and memory networkssubnetworks The fMRI and behavioral performance effects on memory will be greater in the MCI and mild AD groups than in the healthy aging group The effects will be greater in the MCI and AD groups than in the control groups
Power analysis Sample sizes were calculated using an fMRI power tool based on pilot data from the current study for a power of 80 alpha 005 False Discovery Rate 005 to detect statistical difference between MB and placebo23 The investigators estimate they will need 20-25 subjects per arm of group complete studies and thus will recruit 200-240 subjects to account for potential failed studies
fMRI and behavioral data will be collected simultaneously while inside the scanner
Delayed match-to-sample task The subject views a pattern for a few seconds and then is prompted to recall the memorized pattern using a response system approx 10 mins
Face-name task The subject is shown blocks of stimuli where a novel or familiar face is paired with a name In a later run the subjects are asked whether the correct name is matched with the correct face approx 10 mins
Psychomotor vigilance task The subject receives a visual cue that alerts them to press a button as fast as possible approx 10 mins
Cerebral Blood Flow and Resting State fMRI Subject scanned with eyes closed and told to not think about a particular topic each lasting about 10 minutes
fMRI data acquisition fMRI and neuropsychological battery measurements will be made before the intervention These measurements will then be repeated after 2 weeks and 12 weeks
fMRI will image changes in regional brain activity associated with these tasks The MRI pulse sequences include diffusion tensor imaging standard and non-invasive anatomical and quantitative MRI for coregistration and blood-oxygen-level dependent BOLD fMRI
CO2 challenge Cerebral blood flow measurements will be obtained while the subject rests in the scanner after administration of medical-grade 5 CO2 in air for 3-5 minutes This will be repeated on weeks 2 and 12
Data analysis Standard fMRI analysis will be analyzed using established fMRI software Statistical parametric analysis will be performed to generate activation maps fMRI data will be corrected for multiple comparisons using a false discovery rate q 005 and threshold for cluster values to conservatively control for type I error Behavioral data will be analyzed with paired t-test and ANOVA calculations used for group comparison with p 005 with Bonferroni correction considered statistically significant
Expected results The investigators predict that compared to placebo MB will i improve working memory retention in a delayed match-to-sample task by memory performance and enhanced fMRI responses in the prefrontal cortex and parietal lobes ii improve episodic memory as determined by fMRI activation in the hippocampus medial temporal lobes and prefrontal cortex iii reduce reaction time in a psychomotor vigilance test and enhance fMRI responses within a cortical sustained attention network iv improve CBF and v improve fMRI connectivity in default mode and visuospatial and memory networkssubnetworks The fMRI and behavioral performance effects on memory will be greater in the MCI and mild AD groups than in the healthy aging group The effects will be greater in the MCI and AD groups than in the control groups
Power analysis Sample sizes were calculated using an fMRI power tool based on pilot data from the current study for a power of 80 alpha 005 False Discovery Rate 005 to detect statistical difference between MB and placebo23 The investigators estimate they will need 20-25 subjects per arm of group complete studies and thus will recruit 200-240 subjects to account for potential failed studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None