Aging Clinical Trial
— MB2Official title:
Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease
Verified date | August 2022 |
Source | The University of Texas Health Science Center at San Antonio |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 117 |
Est. completion date | July 2023 |
Est. primary completion date | April 21, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 45 Years to 89 Years |
Eligibility | Inclusion Criteria for all subjects: 1. 45-89 years old 2. All genders 3. All minorities 4. English, Spanish, or multilingual speakers 5. Postmenopausal or surgically sterile females only. 6. Inclusion for MCI group only: participants will meet the criteria for amnestic and non-amnestic MCI such as those currently used by Texas Alzheimer's Research and Care Consortium (TARCC) consensus diagnosis 7. Inclusion for AD group only: Alzheimer's Early-stage, sporadic-type Exclusion Criteria: 1. Pregnancy or breastfeeding 2. Contraindication for MRI (Claustrophobia and magnetic metal implants) 3. Glucose-6-phosphate deficiency, methemoglobinemia 4. Allergy to MB 5. Color-blindness 6. Craniotomy, craniectomy or endovascular neurosurgery 7. A current diagnosis of stroke, transient ischemic attack (TIA), any primary neurodegenerative disorder, or any other causes of neuropsychologic disturbances or secondary dementia (MCI or AD does not exclude subject) 8. A serious intercurrent illness likely to cause death within the next 5 years, such as terminal cancer 9. Alcohol and/or drug abuse 10. Any detection of an unknown disease process (eg. new tumor) on the study's neuroimaging at the discretion of the investigators 11. A systolic blood pressure =180 mmHg and/or a diastolic blood pressure =105 mmHg 12. Severe difficulty or an inability to perform any one of the 6 Katz Activities of Daily Living 13. Patients who are unlikely to comply with trial visit schedule or with trial medication, 14. On any psychiatric serotonergic antidepressant medication or psychotropic medication within the last 5 weeks 15. Diagnosis of epilepsy, traumatic brain injury with loss of consciousness, psychosis, panic attacks, 16. Chronic kidney disease, cirrhosis, liver or renal transplants 17. Known hypersensitivity to thiazide diuretics and phenothiazines 18. Any other condition, which in the opinion of the investigator, would put the participant at risk and warrant exclusion from the study |
Country | Name | City | State |
---|---|---|---|
United States | Research Imaging Institute, The University of Texas Health Science Center at San Antonio | San Antonio | Texas |
Lead Sponsor | Collaborator |
---|---|
The University of Texas Health Science Center at San Antonio | Texas Alzheimer's Research and Care Consortium (TARCC) |
United States,
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. — View Citation
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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. — View Citation
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. — View Citation
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. — View Citation
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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. — View Citation
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. Review. — View Citation
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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. — View Citation
* Note: There are 15 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Functional Connectivity measures | fMRI measurements will be obtained while the subject rests in the scanner | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Other | CO2 challenge | Cerebral blood flow measurements will be acquired during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Working memory task | fMRI measurement of task blocked activation | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Working memory task response | Working memory task behavioral measures (ie. correct number of responses) | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Episodic memory task | fMRI measurement of task blocked activation | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Episodic memory task response | Face-Name Task behavioral measures (ie. correct recalls) | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Sustained attention task | fMRI measurement of task blocked activation | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Sustained attention task reaction time | Psychomotor vigilance task (PVT) behavioral measures (ie. reaction time) | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Primary | Neuropsychological battery composite score | TARCC designed neurocognitive tests | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days | |
Secondary | Cerebral blood flow measures | Resting measurements will be used to assess response and CBF using fMRI | baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days |
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