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Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease (MB2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by The University of Texas Health Science Center at San Antonio
Sponsor:
Collaborator:
Texas Alzheimer’s Research and Care Consortium (TARCC)
Information provided by (Responsible Party):
Peter Fox, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT02380573
First received: February 24, 2015
Last updated: July 21, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Mild Cognitive Impairment
MCI
Aging
Alzheimer's Disease
AD
Drug: Methylene Blue
Drug: FD&C Blue # 2
Drug: Phenazopyridine hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Working memory task fMRI [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    fMRI task blocked activation

  • Working memory task response [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    Working memory task behavioral measures (ie. correct number of responses)

  • Episodic memory task fMRI [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    fMRI task blocked activation

  • Episodic memory task response [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    Face-Name Task behavioral measures (ie. correct recalls)

  • Sustained attention task fMRI [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    fMRI task blocked activation

  • Sustained attention task reaction time [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    Psychomotor vigilance task (PVT) behavioral measures (ie. reaction time)

  • Neuropsychological battery composite score [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    TARCC designed neurocognitive tests


Secondary Outcome Measures:
  • Cerebral blood flow fMRI measures [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    Resting measurements will be used to assess response and CBF


Other Outcome Measures:
  • Functional Connectivity fMRI measures [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    fMRI measurements will be obtained while the subject rests in the scanner

  • CO2 challenge [ Time Frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days ]
    Cerebral blood flow measurements will be acquired during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air.


Estimated Enrollment: 240
Study Start Date: July 2015
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy Aging MB
Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks)
Drug: Methylene Blue
Other Name: Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Placebo Comparator: 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)
Drug: FD&C Blue # 2
Other Name: Placebo
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Experimental: 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)
Drug: Methylene Blue
Other Name: Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Placebo Comparator: 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)
Drug: FD&C Blue # 2
Other Name: Placebo
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Experimental: 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)
Drug: Methylene Blue
Other Name: Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Placebo Comparator: 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)
Drug: FD&C Blue # 2
Other Name: Placebo
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Experimental: Health 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)
Drug: Methylene Blue
Other Name: Phenothiazin-5-ium, 3, 7-bis (dimethylamino)-chloride, trihydrate
Drug: Phenazopyridine hydrochloride
Other Name: Azo
Placebo Comparator: Health 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)
Drug: FD&C Blue # 2
Other Name: Placebo
Drug: Phenazopyridine hydrochloride
Other Name: Azo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   45 Years to 89 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02380573

Contacts
Contact: Peter Fox, MD 210-567-8150 Fox@uthscsa.edu
Contact: Pavel Rodriguez, MD 210-567-8173 rodriguezp3@uthscsa.edu

Locations
United States, Texas
Research Imaging Institute, The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Pavel Rodriguez, MD    210-567-8173    rodriguezp3@uthscsa.edu   
Contact: Linda Hubbard, RN    210-567-5604    hubbardl@uthscsa.edu   
Principal Investigator: Peter T. Fox, MD         
Sub-Investigator: Timothy Q. Duong, PhD         
Sub-Investigator: Pavel Rodriguez, MD         
Sub-Investigator: Donald R. Royall, MD         
Sponsors and Collaborators
Peter Fox
Texas Alzheimer’s Research and Care Consortium (TARCC)
  More Information

Additional Information:
Publications:

Responsible Party: Peter Fox, Professor, Research Imaging Institute Chair, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02380573     History of Changes
Other Study ID Numbers: HSC20150410H
Study First Received: February 24, 2015
Last Updated: July 21, 2016

Keywords provided by The University of Texas Health Science Center at San Antonio:
methylene blue
fMRI

Additional relevant MeSH terms:
Methylene Blue
Alzheimer Disease
Mild Cognitive Impairment
Cognition Disorders
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 22, 2017