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| Name | Class |
|---|---|
| Texas Alzheimer's Research and Care Consortium | OTHER |
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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 Alzheimer's disease (AD) subjects.
Healthy aging and aging human subjects with mild cognitive impairment and mild Alzheimer's 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 < 0.05) 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 < 0.05 (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 networks/subnetworks. 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 = 0.05, False Discovery Rate < 0.05, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Aging MB | Experimental | Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| Healthy Aging Placebo | Placebo Comparator | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| Mild Cognitive Impairment (MCI) MB | Experimental | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| Mild Cognitive Impairment (MCI) Placebo | Placebo Comparator | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| Mild Alzheimer's Disease (AD) MB | Experimental | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylene Blue | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| fMRI Measurement | fMRI measurement of task blocked activation during Wechsler Memory Scale III | baseline, 2 weeks and 12 weeks |
| Wechsler Memory Scale, Third Edition | Working memory task behavioral measures (ie. correct number of responses) Score is 0-104, with higher scores being better. | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| fMRI During FNAME | Functional Magnetic Resonance Imaging (fMRI) measurement of task blocked activation. Measure reflects blood flow counts, and is not a scale with a high or low score. | baseline, 2 weeks ± 3 days,12 weeks ± 3 days |
| FNAME | Face-Name Task behavioral measures (ie. correct recalls). The FNAME is a cross-modal associative memory test which includes 16 face-name pairs and 16 face-occupation pairs, with a total of 32 pairs to remember. Scores range from 0-32, higher scores are better | baseline, 2 weeks ± 3 days,12 weeks ± 3 days |
| fMRI During Psychomotor Vigilance Task | fMRI measurement of task blocked activation | baseline,2 weeks ± 3 days,12 weeks ± 3 days |
| Psychomotor Vigilance Task | Psychomotor vigilance task (PVT) behavioral measures (ie. reaction time). The primary outcome measures of PVT performance, lapses, are defined as reaction times exceeding 500 msec or failure to react. The PVT lapses are believed to represent perceptual, processing, or executive failures in the central nervous system (CNS) Lower scores are better, as they indicate quicker reaction times. |
| Measure | Description | Time Frame |
|---|---|---|
| Cerebral Blood Flow Measures | Resting measurements will be used to assess response and CBF using fMRI. Scores are baseline, percent change between baseline and 2 weeks, baseline and 12 weeks | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| Measure | Description | Time Frame |
|---|---|---|
| Functional Connectivity Measures | Functional magnetic resonance imaging (fMRI) measurements will be obtained while the subject rests in the scanner, with their eyes closed. The default mode network (DMN) will be identified from the resting state data using temporal concatenation independent components analysis. Dual regression will then be applied to identify the individual subject's DMN maps, followed by the counting of significant voxels above threshold within the DMN masks. This will be repeated on weeks 2 and 12. the voxel is a 3-dimensional unit that embeds the signals in brain scans. As the MRI machine scans through each dimension of the brain millimeter by millimeter, voxels are formed to enclose the signals created by protons-magnet interactions. |
Inclusion Criteria for all subjects:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Imaging Institute, The University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20463863 | Background | Bruchey 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. | |
| 22067440 | Background | Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012 Jan;96(1):32-45. doi: 10.1016/j.pneurobio.2011.10.007. Epub 2011 Nov 3. |
| Label | URL |
|---|---|
| Texas Alzheimer's Research and Care Consortium | View source |
Not provided
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Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Aging MB | Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| FG001 | Healthy Aging Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 6, 2015 |
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|
| Mild Alzheimer's Disease (AD) Placebo | Placebo Comparator | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| Healthy Middle Age MB | Experimental | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| Healthy Middle Age Placebo | Placebo Comparator | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
| FD&C Blue # 2 | Drug |
|
|
| Phenazopyridine hydrochloride | Drug |
|
|
| baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days |
| Wechsler Memory Scale III, Logical Memory Subset | The patient is read two stories, out loud, by the test administrator. After each story is read, the patient is then asked to tell the story back to the administrator, as well as possible. Scores range from 0-75, with higher scores indicating better outcome. | baseline, then 12 weeks ± 3 days |
| Mini-Mental State Exam (MMSE) | Short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings. The MMSE contains 11 questions with scores ranging from 1-5 depending on how many responses are required for each question. One point is assigned for each correct answer. The total score can range from 0-30 with a higher score indicating better cognitive skills. | baseline, 2 weeks ± 3 days,12 weeks ± 3 days |
| CLOX: An Executive Clock Drawing Test | The subject draws a clock that says 1:45. Performance is rated according to the CLOX directions, and scored as "CLOX1" with scores ranging from 0-15 with a lower score indicating greater impairment. CLOX1 reflects performance in a novel and ambiguous situation. The CLOX's second step is a simple copying task. The examiner allows the patient to observe him or her drawing a clock in the circle provided on the scoring sheet. The examiner sets the hands again to "1:45", places the 12, 6, 3, and 9 first, and makes the hands into arrows. The patient is allowed to copy the examiner's clock. This clock is scored as "CLOX2" with scores ranging from 0-15 with a lower score indicating greater impairment. Participants can earn up to 15 points for each test, this is summed to give a possible score out of 30 with a higher score indicating less cognitive impairment. Scores reported are from inter-rater reliability | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| CO2 Challenge | Cerebral blood flow measurements will be acquired during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. Cerebral blood flow measurements will be obtained using Arterial Spin Labeling (ASL) during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. Mean regional CBF (rCBF) in gray matter is quantified as ml/100g/min of tissue. The percent change from baseline will be calculated. This will be repeated on weeks 2 and 12. | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days |
| 25018057 | Background | Telch MJ, Bruchey AK, Rosenfield D, Cobb AR, Smits J, Pahl S, Gonzalez-Lima F. Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia. Am J Psychiatry. 2014 Oct;171(10):1091-8. doi: 10.1176/appi.ajp.2014.13101407. |
| 23056355 | Background | Lin AL, Poteet E, Du F, Gourav RC, Liu R, Wen Y, Bresnen A, Huang S, Fox PT, Yang SH, Duong TQ. Methylene blue as a cerebral metabolic and hemodynamic enhancer. PLoS One. 2012;7(10):e46585. doi: 10.1371/journal.pone.0046585. Epub 2012 Oct 9. |
| 23357077 | Background | Huang S, Du F, Shih YY, Shen Q, Gonzalez-Lima F, Duong TQ. Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia. Neuroimage. 2013 May 15;72:237-42. doi: 10.1016/j.neuroimage.2013.01.027. Epub 2013 Jan 26. |
| 24479842 | Background | Talley Watts L, Long JA, Chemello J, Van Koughnet S, Fernandez A, Huang S, Shen Q, Duong TQ. Methylene blue is neuroprotective against mild traumatic brain injury. J Neurotrauma. 2014 Jun 1;31(11):1063-71. doi: 10.1089/neu.2013.3193. Epub 2014 Apr 8. |
| 25203249 | Background | Long JA, Watts LT, Chemello J, Huang S, Shen Q, Duong TQ. Multiparametric and longitudinal MRI characterization of mild traumatic brain injury in rats. J Neurotrauma. 2015 Apr 15;32(8):598-607. doi: 10.1089/neu.2014.3563. Epub 2015 Jan 22. |
| 25218555 | Background | Rodriguez P, Jiang Z, Huang S, Shen Q, Duong TQ. Methylene blue treatment delays progression of perfusion-diffusion mismatch to infarct in permanent ischemic stroke. Brain Res. 2014 Nov 7;1588:144-9. doi: 10.1016/j.brainres.2014.09.007. Epub 2014 Sep 8. |
| 24278191 | Background | Shen Q, Du F, Huang S, Rodriguez P, Watts LT, Duong TQ. Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study. PLoS One. 2013 Nov 21;8(11):e79833. doi: 10.1371/journal.pone.0079833. eCollection 2013. |
| 10952480 | Background | Peter C, Hongwan D, Kupfer A, Lauterburg BH. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000 Jun;56(3):247-50. doi: 10.1007/s002280000124. |
| 15466319 | Background | Gonzalez-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. |
| 3091097 | Background | Naylor GJ, Martin B, Hopwood SE, Watson Y. A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis. Biol Psychiatry. 1986 Aug;21(10):915-20. doi: 10.1016/0006-3223(86)90265-9. |
| 4875885 | Background | Mackworth JF. Vigilance, arousal, and habituation. Psychol Rev. 1968 Jul;75(4):308-22. doi: 10.1037/h0025896. No abstract available. |
| 15954139 | Background | Rombouts SA, Barkhof F, Goekoop R, Stam CJ, Scheltens P. Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study. Hum Brain Mapp. 2005 Dec;26(4):231-9. doi: 10.1002/hbm.20160. |
| 23481166 | Background | Wang L, Li H, Liang Y, Zhang J, Li X, Shu N, Wang YY, Zhang Z. Amnestic mild cognitive impairment: topological reorganization of the default-mode network. Radiology. 2013 Aug;268(2):501-14. doi: 10.1148/radiol.13121573. Epub 2013 Mar 12. |
| Research Imaging Institute | View source |
Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks)
FD&C Blue # 2
Phenazopyridine hydrochloride
| FG002 | Mild Cognitive Impairment (MCI) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| FG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| FG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| FG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| FG006 | Healthy Middle Age MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| FG007 | Healthy Middle Age Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| COMPLETED |
|
| NOT COMPLETED |
|
Because this was a study of aging people, participants under the age of 18 were not included.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Aging MB | Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| BG001 | Healthy Aging Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| BG002 | Mild Cognitive Impairment (MCI) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| BG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| BG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| BG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| BG006 | Healthy Middle Age MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| BG007 | Healthy Middle Age Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | fMRI Measurement | fMRI measurement of task blocked activation during Wechsler Memory Scale III | There was not sufficient data collected to be analyzed for Mild Alzheimer's disease MB or placebo, only the scale score was measured, as reported in the Wechsler Memory Scale outcome. | Posted | Mean | Standard Deviation | voxels | baseline, 2 weeks and 12 weeks |
|
|
| ||||||||||||||||||||||||||||||||||||||||
| Primary | Wechsler Memory Scale, Third Edition | Working memory task behavioral measures (ie. correct number of responses) Score is 0-104, with higher scores being better. | Posted | Mean | Standard Deviation | score on a scale | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Primary | fMRI During FNAME | Functional Magnetic Resonance Imaging (fMRI) measurement of task blocked activation. Measure reflects blood flow counts, and is not a scale with a high or low score. | There was not sufficient data collected to be analyzed for Mild Alzheimer's disease MB or placebo, only the scale measure was obtained in the next outcome. | Posted | Mean | Standard Deviation | voxels activated over a threshold | baseline, 2 weeks ± 3 days,12 weeks ± 3 days |
| ||||||||||||||||||||||||||||||||||||||||||
| Primary | FNAME | Face-Name Task behavioral measures (ie. correct recalls). The FNAME is a cross-modal associative memory test which includes 16 face-name pairs and 16 face-occupation pairs, with a total of 32 pairs to remember. Scores range from 0-32, higher scores are better | Posted | Mean | Standard Deviation | score on a scale | baseline, 2 weeks ± 3 days,12 weeks ± 3 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Primary | fMRI During Psychomotor Vigilance Task | fMRI measurement of task blocked activation | There was no data collected to be analyzed for Mild Alzheimer's disease MB or placebo. | Posted | Mean | Standard Deviation | # voxels beyond a threshold | baseline,2 weeks ± 3 days,12 weeks ± 3 days |
| ||||||||||||||||||||||||||||||||||||||||||
| Primary | Psychomotor Vigilance Task | Psychomotor vigilance task (PVT) behavioral measures (ie. reaction time). The primary outcome measures of PVT performance, lapses, are defined as reaction times exceeding 500 msec or failure to react. The PVT lapses are believed to represent perceptual, processing, or executive failures in the central nervous system (CNS) Lower scores are better, as they indicate quicker reaction times. | Posted | Mean | Standard Deviation | milliseconds | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Primary | Wechsler Memory Scale III, Logical Memory Subset | The patient is read two stories, out loud, by the test administrator. After each story is read, the patient is then asked to tell the story back to the administrator, as well as possible. Scores range from 0-75, with higher scores indicating better outcome. | Not all participants came back for all three visits. | Posted | Mean | Standard Deviation | score on a scale | baseline, then 12 weeks ± 3 days |
| ||||||||||||||||||||||||||||||||||||||||||
| Primary | Mini-Mental State Exam (MMSE) | Short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings. The MMSE contains 11 questions with scores ranging from 1-5 depending on how many responses are required for each question. One point is assigned for each correct answer. The total score can range from 0-30 with a higher score indicating better cognitive skills. | Not all participants returned for all three visits. | Posted | Mean | Standard Deviation | score on a scale | baseline, 2 weeks ± 3 days,12 weeks ± 3 days |
| ||||||||||||||||||||||||||||||||||||||||||
| Primary | CLOX: An Executive Clock Drawing Test | The subject draws a clock that says 1:45. Performance is rated according to the CLOX directions, and scored as "CLOX1" with scores ranging from 0-15 with a lower score indicating greater impairment. CLOX1 reflects performance in a novel and ambiguous situation. The CLOX's second step is a simple copying task. The examiner allows the patient to observe him or her drawing a clock in the circle provided on the scoring sheet. The examiner sets the hands again to "1:45", places the 12, 6, 3, and 9 first, and makes the hands into arrows. The patient is allowed to copy the examiner's clock. This clock is scored as "CLOX2" with scores ranging from 0-15 with a lower score indicating greater impairment. Participants can earn up to 15 points for each test, this is summed to give a possible score out of 30 with a higher score indicating less cognitive impairment. Scores reported are from inter-rater reliability | It was determined after the study began that recruiting middle aged subjects would not be worthwhile. | Posted | Mean | Standard Deviation | score on a scale | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| ||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cerebral Blood Flow Measures | Resting measurements will be used to assess response and CBF using fMRI. Scores are baseline, percent change between baseline and 2 weeks, baseline and 12 weeks | Posted | Mean | Standard Deviation | percentage of change | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Functional Connectivity Measures | Functional magnetic resonance imaging (fMRI) measurements will be obtained while the subject rests in the scanner, with their eyes closed. The default mode network (DMN) will be identified from the resting state data using temporal concatenation independent components analysis. Dual regression will then be applied to identify the individual subject's DMN maps, followed by the counting of significant voxels above threshold within the DMN masks. This will be repeated on weeks 2 and 12. the voxel is a 3-dimensional unit that embeds the signals in brain scans. As the MRI machine scans through each dimension of the brain millimeter by millimeter, voxels are formed to enclose the signals created by protons-magnet interactions. | Posted | Mean | Standard Deviation | Voxels | baseline, 2 weeks ± 3 days, 12 weeks ± 3 days |
| |||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | CO2 Challenge | Cerebral blood flow measurements will be acquired during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. Cerebral blood flow measurements will be obtained using Arterial Spin Labeling (ASL) during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. Mean regional CBF (rCBF) in gray matter is quantified as ml/100g/min of tissue. The percent change from baseline will be calculated. This will be repeated on weeks 2 and 12. | Posted | Mean | Standard Deviation | percentage change from baseline | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days |
|
Adverse events were collected from the time of randomization to 12 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Aging MB | Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride | 0 | 22 | 0 | 22 | 22 | 22 |
| EG001 | Healthy Aging Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride | 0 | 21 | 0 | 21 | 19 | 21 |
| EG002 | Mild Cognitive Impairment (MCI) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride | 0 | 28 | 0 | 28 | 27 | 28 |
| EG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride | 0 | 24 | 0 | 24 | 21 | 24 |
| EG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) | 0 | 1 | 0 | 1 | 0 | 1 |
| EG005 | Mild Alzheimer's Disease (AD) Placebo | FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) | 0 | 1 | 0 | 1 | 0 | 1 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| blue or orange urine | Renal and urinary disorders | Systematic Assessment | blue or orange urine |
| |
| green stool | Gastrointestinal disorders | Systematic Assessment | stool turned green |
| |
| urinary frequency or urgency | Renal and urinary disorders | Systematic Assessment | increased urinary frequency |
| |
| vomiting or nausea | Gastrointestinal disorders | Systematic Assessment | vomiting or nausea |
| |
| diarrhea/loose stool | Gastrointestinal disorders | Systematic Assessment | diarrhea or loose stool |
| |
| hot flashes | General disorders | Systematic Assessment | flashes of heat |
| |
| bladder irritation | Renal and urinary disorders | Systematic Assessment | irritation of bladder |
| |
| leg cramps | Musculoskeletal and connective tissue disorders | Systematic Assessment | leg cramps |
| |
| decreased libido | Social circumstances | Systematic Assessment | decreased in libido |
| |
| fever | General disorders | Systematic Assessment | fever |
| |
| skin | Skin and subcutaneous tissue disorders | Systematic Assessment | skin problems |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Peter Fox | University of Texas Health Science Center at San Antonio | 210-567-8150 | fox@uthscsa.edu |
| Mar 20, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008751 | Methylene Blue |
| D007203 | Indigo Carmine |
| D010621 | Phenazopyridine |
| ID | Term |
|---|---|
| D010640 | Phenothiazines |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000631 | Aminopyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| White, Hispanic |
|
| Pacific Islander, Non-Hispanic |
|
| Pacific Islander, Hispanic |
|
| Black, Non-Hispanic |
|
| Black, Hispanic |
|
| Asian, Non-Hispanic |
|
| Asian, Hispanic |
|
| White, Not Specified |
|
| Not Specified, Not Specified |
|
| 2 weeks |
|
| 12 weeks |
|
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
| OG003 |
| Mild Cognitive Impairment (MCI) Placebo |
Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG006 | Healthy Middle Age MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
| OG007 | Healthy Middle Age Placebo | FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
|
Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks)
FD&C Blue # 2
Phenazopyridine hydrochloride
| OG004 | Mild Alzheimer's Disease MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
| OG005 | Mild Alzheimer's Disease Placebo | FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) |
|
|
| OG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
| Mild Cognitive Impairment (MCI) Placebo |
Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
| OG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
| OG002 | Mild Cognitive Impairment (MCI) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
| OG004 | AD MB | Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | AD Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
|
| OG003 | Mild Cognitive Impairment (MCI) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
| OG004 | Mild Alzheimer's Disease (AD) MB | Methylene Blue (USP grade, 282 mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) Methylene Blue Phenazopyridine hydrochloride |
| OG005 | Mild Alzheimer's Disease (AD) Placebo | Drug: FD&C Blue # 2 (USP grade, 282 mg oral, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks) FD&C Blue # 2 Phenazopyridine hydrochloride |
|
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