MB2

CompletedPhase 2Results posted

Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease

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

Lead sponsor

The University of Texas Health Science Center at San Antonio

Asset

Methylene Blue

Listed sites

Recruiting sites

Enrollment

117

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•MRI contraindications excluded

Primary endpoints

•FMRI Measurement•Wechsler Memory Scale, Third Edition•FMRI During FNAME

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDHSC20150410H

NCT IDNCT02380573

Timeline

Milestones

Study first posted2015-03-05estimated

Study start2015-07 (month precision)

Primary completion2022-04-21actual

Study completion2023-07actual (month precision)

Last update posted2024-09-19actual

Results first posted2024-09-19actual

Assets

Drug assets

Methylene Blue

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age45 Years

Maximum age89 Years

SexAll

Healthy volunteersAccepted

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

Endpoints (24)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Neuroimaging

Memory

Other (unclassified)

Global cognition

2 endpoints

Primary/protocol endpoint

Mini-Mental State Exam (MMSE)

Time frame:baseline, 2 weeks ± 3 days,12 weeks ± 3 days

Mini-Mental State Examination (MMSE)

descriptive

Primary/registry result

Mini-Mental State Exam (MMSE)

Time frame:baseline, 2 weeks ± 3 days,12 weeks ± 3 days

Mini-Mental State Examination (MMSE)

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Healthy Aging MBbaselinen=21 Participants	29	1.05
3 weeksn=21 Participants	29.7	.66
12 weeksn=12 Participants	29.9	.58
Healthy Aging Placebobaselinen=19 Participants	29.32	.95
3 weeksn=19 Participants	29.6	.61
12 weeksn=13 Participants	29.3	1.11
Mild Cognitive Impairment (MCI) MBbaselinen=21 Participants	27.76	1.9
3 weeksn=21 Participants	28.3	1.15
12 weeksn=16 Participants	28.5	1.4
Mild Cognitive Impairment (MCI) Placebobaselinen=21 Participants	27.52	1.86
3 weeksn=21 Participants	27.7	2.4
12 weeksn=12 Participants	28.25	1.1
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	21	0
3 weeksn=1 Participants	26	0
12 weeksn=1 Participants	24	0
Mild Alzheimer's Disease (AD) Placebobaselinen=2 Participants	21	0
3 weeksn=2 Participants	20	0
12 weeksn=2 Participants	24	0

Memory

8 endpoints

Primary/protocol endpoint

fMRI Measurement

Time frame:baseline, 2 weeks and 12 weeks

descriptive

Primary/protocol endpoint

Wechsler Memory Scale, Third Edition

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

event count, event

Primary/protocol endpoint

FNAME

Time frame:baseline, 2 weeks ± 3 days,12 weeks ± 3 days

descriptive

Primary/protocol endpoint

Wechsler Memory Scale III, Logical Memory Subset

Time frame:baseline, then 12 weeks ± 3 days

descriptive

Primary/registry result

fMRI Measurement

Time frame:baseline, 2 weeks and 12 weeks

descriptive

Posted result

Group	Value (mean), voxels	Standard deviation
Healthy Aging MBBaselinen=12 Participants	2267.0	2428.23
2 weeksn=12 Participants	1719.00	1377.02
12 weeksn=12 Participants	1451.83	1623.84
Healthy Aging PlaceboBaselinen=13 Participants	1491.23	1343.81
2 weeksn=13 Participants	962.69	843.93
12 weeksn=13 Participants	1623.84	919.08
Mild Cognitive Impairment (MCI) MBBaselinen=12 Participants	673.31	1366.69
2 weeksn=12 Participants	12270.59	1955.60
12 weeksn=12 Participants	1238.58	1743.67
Mild Cognitive Impairment (MCI) PlaceboBaselinen=16 Participants	989.19	1651.97
2 weeksn=16 Participants	930.25	1157.55
12 weeksn=16 Participants	1334.38	2341.44

Primary/registry result

Wechsler Memory Scale, Third Edition

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

event count, event

Posted result

Group	Value (mean), score on a scale	Standard deviation
Healthy Aging MBbaselinen=12 Participants	14.58	2.35
2 weeksn=12 Participants	16	2.3
12 weeksn=12 Participants	15.58	2.11
Healthy Aging Placebobaselinen=14 Participants	15.43	2.85
2 weeksn=14 Participants	17.29	1.33
12 weeksn=14 Participants	15.93	2.13
Mild Cognitive Impairment (MCI) MBbaselinen=13 Participants	15.23	2.5
2 weeksn=13 Participants	15.23	2.68
12 weeksn=13 Participants	14.69	1.55
Mild Cognitive Impairment (MCI) Placebobaselinen=15 Participants	13.06	3.23
2 weeksn=15 Participants	15.31	2.94
12 weeksn=15 Participants	13.2	3.17
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	4	0
2 weeksn=1 Participants	5	0
12 weeksn=1 Participants	11	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	15	0
2 weeksn=1 Participants	17	0
12 weeksn=1 Participants	13	0

Primary/registry result

FNAME

Time frame:baseline, 2 weeks ± 3 days,12 weeks ± 3 days

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Healthy Aging MBbaselinen=12 Participants	14.5	4.83
2 weeksn=12 Participants	16.08	4.7
12 weeksn=12 Participants	16.67	4.16
Healthy Aging Placebobaselinen=14 Participants	14.36	4.86
2 weeksn=14 Participants	15.36	6.1
12 weeksn=14 Participants	16	6.24
Mild Cognitive Impairment (MCI) MBbaselinen=13 Participants	10.54	3.71
2 weeksn=13 Participants	12.54	4.52
12 weeksn=13 Participants	14	3.96
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	11.19	4.23
2 weeksn=16 Participants	11.5	4.62
12 weeksn=16 Participants	12.69	5.62
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	8	0
2 weeksn=1 Participants	2	0
12 weeksn=1 Participants	6	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	6	0
2 weeksn=1 Participants	9	0
12 weeksn=1 Participants	1	0

Primary/registry result

Wechsler Memory Scale III, Logical Memory Subset

Time frame:baseline, then 12 weeks ± 3 days

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Healthy Aging MBbaselinen=20 Participants	47	9.5
12 weeksn=12 Participants	48	10.1
Healthy Aging Placebobaselinen=19 Participants	43.5	9.5
12 weeksn=13 Participants	41.1	9.1
Mild Cognitive Impairment (MCI) MBbaselinen=21 Participants	32.4	9.66
12 weeksn=16 Participants	33.5	7.9
Mild Cognitive Impairment (MCI) Placebobaselinen=21 Participants	37.48	9.8
12 weeksn=12 Participants	37.06	7.7
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	25	0
12 weeksn=1 Participants	21	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	5	0
12 weeksn=1 Participants	5	0

Neuroimaging

10 endpoints

Primary/protocol endpoint

fMRI During FNAME

Time frame:baseline, 2 weeks ± 3 days,12 weeks ± 3 days

descriptive

Primary/protocol endpoint

fMRI During Psychomotor Vigilance Task

Time frame:baseline,2 weeks ± 3 days,12 weeks ± 3 days

descriptive

Primary/registry result

fMRI During FNAME

Time frame:baseline, 2 weeks ± 3 days,12 weeks ± 3 days

descriptive

Posted result

Group	Value (mean), voxels activated over a threshold	Standard deviation
Healthy Aging MBbaselinen=12 Participants	16881.03	8823.60
2 weeksn=12 Participants	18146.92	7075.66
12 weeksn=12 Participants	16893.83	6689.61
Healthy Aging Placebobaselinen=13 Participants	17382.29	6401.56
2 weeksn=13 Participants	19748.86	8221.18
12 weeksn=13 Participants	18342.57	8230.30
Mild Cognitive Impairment (MCI) MBbaselinen=12 Participants	13166.23	4796.32
2 weeksn=12 Participants	12935.15	7042.78
12 weeksn=12 Participants	13973.56	10759.77
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	13777.75	8955.52
2 weeksn=16 Participants	15617.31	7519.81
12 weeksn=16 Participants	14466.56	9944.16
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	2211.00	0
2 weeksn=1 Participants	4939.00	0
12 weeksn=1 Participants	2240.00	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	3938.00	0
2 weeksn=1 Participants	4140.00	0
12 weeksn=1 Participants	1355.00	0

Primary/registry result

fMRI During Psychomotor Vigilance Task

Time frame:baseline,2 weeks ± 3 days,12 weeks ± 3 days

descriptive

Posted result

Group	Value (mean), # voxels beyond a threshold	Standard deviation
Healthy Aging MBbaselinen=12 Participants	271.33	590.79
2 weeksn=12 Participants	175.08	370.05
12 weeksn=12 Participants	66.25	94.43
Healthy Aging Placebobaselinen=13 Participants	150.79	348.98
2 weeksn=13 Participants	129.00	230.28
12 weeksn=13 Participants	47.43	105.62
Mild Cognitive Impairment (MCI) MBbaselinen=12 Participants	145.00	321.47
2 weeksn=12 Participants	89.54	173.65
12 weeksn=12 Participants	156.77	330.64
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	56.94	220.91
2 weeksn=16 Participants	75.31	148.86
12 weeksn=16 Participants	13.88	38.76

Secondary/protocol endpoint

Cerebral Blood Flow Measures

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

percent change from baseline, improvement

Secondary/registry result

Cerebral Blood Flow Measures

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

percent change from baseline, improvement

Posted result

Group	Value (mean), percentage of change	Standard deviation
Healthy Aging MBbaselinen=12 Participants	34.65	15.62
% change, baseline vs 2 weeksn=12 Participants	36.1	22.9
% change, baseline vs 12 weeksn=12 Participants	40.89	29
Healthy Aging Placebobaselinen=13 Participants	37.9	49
% change, baseline vs 2 weeksn=13 Participants	35.97	27.3
% change, baseline vs 12 weeksn=13 Participants	42.13	32.6
Mild Cognitive Impairment (MCI) MBbaselinen=12 Participants	31.97	16
% change, baseline vs 2 weeksn=12 Participants	31.97	16
% change, baseline vs 12 weeksn=12 Participants	57.07	64.1
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	35.2	35
% change, baseline vs 2 weeksn=16 Participants	31.55	14.84
% change, baseline vs 12 weeksn=16 Participants	35.2	14.85
AD MBbaselinen=1 Participants	95.13	0
% change, baseline vs 2 weeksn=1 Participants	35.85	0
% change, baseline vs 12 weeksn=1 Participants	-1.91	0
AD Placebobaselinen=1 Participants	4.02	0
% change, baseline vs 2 weeksn=1 Participants	23.93	0
% change, baseline vs 12 weeksn=1 Participants	48.57	0

Other/protocol endpoint

Functional Connectivity Measures

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

threshold achievement, improvement

Other/protocol endpoint

CO2 Challenge

Time frame:baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days

percent change from baseline, improvement

Other_pre_specified/registry result

Functional Connectivity Measures

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

threshold achievement, improvement

Posted result

Group	Value (mean), Voxels	Standard deviation
Healthy Aging MBbaselinen=12 Participants	4703.08	735.81
2 weeksn=12 Participants	4778.42	563.19
12 weeksn=12 Participants	4862.75	730.38
Healthy Aging Placebobaselinen=13 Participants	4314.29	943.58
2 weeksn=13 Participants	4066.14	1392.99
12 weeksn=13 Participants	4197.64	1662.41
Mild Cognitive Impairment (MCI) MBbaselinen=12 Participants	4811.23	834.89
2 weeksn=12 Participants	5053.38	956.65
12 weeksn=12 Participants	5124.92	984.09
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	4980	1809.93
2 weeksn=16 Participants	4504.81	1671.78
12 weeksn=16 Participants	4804.81	1128.53
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	3819	0
2 weeksn=1 Participants	5672	0
12 weeksn=1 Participants	4541	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	2990	0
2 weeksn=1 Participants	3566	0
12 weeksn=1 Participants	2006	0

Other_pre_specified/registry result

CO2 Challenge

Time frame:baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days

percent change from baseline, improvement

Posted result

Group	Value (mean), percentage change from baseline	Standard deviation
Healthy Aging MBbaselinen=12 Participants	34.65	15.62
2 weeksn=12 Participants	36.10	22.95
12 weeksn=12 Participants	40.89	29.05
Healthy Aging Placebobaselinen=14 Participants	37.90	49.03
2 weeksn=14 Participants	35.97	27.30
12 weeksn=14 Participants	42.13	32.85
Mild Cognitive Impairment (MCI) MBbaselinen=13 Participants	31.97	16.04
2 weeksn=13 Participants	29.22	24.47
12 weeksn=13 Participants	57.07	64.10
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	35.23	34.99
2 weeksn=16 Participants	31.55	14.85
12 weeksn=16 Participants	35.19	20.83
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	95.13	0
2 weeksn=1 Participants	35.85	0
12 weeksn=1 Participants	-1.91	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	4.02	0
2 weeksn=1 Participants	23.93	0
12 weeksn=1 Participants	48.57	0

Other (unclassified)

4 endpoints

Primary/protocol endpoint/low confidence

Psychomotor Vigilance Task

Time frame:baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days

descriptive

Primary/protocol endpoint/low confidence

CLOX: An Executive Clock Drawing Test

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

descriptive

Primary/registry result/low confidence

Psychomotor Vigilance Task

Time frame:baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days

descriptive

Posted result

Group	Value (mean), milliseconds	Standard deviation
Healthy Aging MBbaselinen=12 Participants	399.9	58.5
2 weeksn=12 Participants	390.1	48.85
12 weeksn=12 Participants	397.5	62.9
Healthy Aging Placebobaselinen=13 Participants	382.7	39.6
2 weeksn=13 Participants	371.86	47.56
12 weeksn=13 Participants	365.33	43.53
Mild Cognitive Impairment (MCI) MBbaselinen=12 Participants	408.1	99
2 weeksn=12 Participants	402.3	66.15
12 weeksn=12 Participants	390.7	80.72
Mild Cognitive Impairment (MCI) Placebobaselinen=16 Participants	482.4	134.5
2 weeksn=16 Participants	456.03	132.94
12 weeksn=16 Participants	455.3	131.5
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	744.8	0
2 weeksn=1 Participants	629	0
12 weeksn=1 Participants	524.7	0
Mild Alzheimer's Disease (AD) Placebobaselinen=1 Participants	631.04	0
2 weeksn=1 Participants	618.83	0
12 weeksn=1 Participants	695.05	0

Primary/registry result/low confidence

CLOX: An Executive Clock Drawing Test

Time frame:baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Healthy Aging MBbaselinen=21 Participants	.89	.96
2 weeksn=21 Participants	.6	.75
12 weeksn=12 Participants	.67	.63
Healthy Aging Placebobaselinen=19 Participants	1	1.33
2 weeksn=19 Participants	.68	1
12 weeksn=13 Participants	.69	1.6
Mild Cognitive Impairment (MCI) MBbaselinen=21 Participants	1.86	1.85
2 weeksn=21 Participants	0.571	0.978
12 weeksn=16 Participants	1	1.13
Mild Cognitive Impairment (MCI) Placebobaselinen=21 Participants	1.52	1.72
2 weeksn=21 Participants	-0.857	1.77
12 weeksn=12 Participants	.86	1.54
Mild Alzheimer's Disease (AD) MBbaselinen=1 Participants	1	0
2 weeksn=1 Participants	2	0
12 weeksn=1 Participants	3	0
Mild Alzheimer's Disease (AD) Placebobaselinen=2 Participants	1	0
2 weeksn=2 Participants	7	0
12 weeksn=2 Participants	4	0

Publications (15)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.