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

Status

Completed

Phase

Phase 2

Enrollment

117 participants (actual)

Sponsor

The University of Texas Health Science Center at San Antonio · Other

Design

Randomized · Quadruple masking

Countries

1 country

United States

Start

Jul 2015

Primary completion

21 Apr 2022

Completion

Jul 2023

First posted

5 Mar 2015 (estimated)

Last update posted

19 Sept 2024

Conditions

Mild Cognitive Impairment · MCI · Aging · Alzheimer's Disease · AD

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.

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• Experimental

  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)

• Placebo comparator

  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)

1. fMRI Measurement

   Time frame · baseline, 2 weeks and 12 weeks

   Registry description

   fMRI measurement of task blocked activation during Wechsler Memory Scale III

2. Wechsler Memory Scale, Third Edition

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

   Registry description

   Working memory task behavioral measures (ie. correct number of responses) Score is 0-104, with higher scores being better.

3. fMRI During FNAME

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

   Registry description

   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.

4. FNAME

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

   Registry description

   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

5. fMRI During Psychomotor Vigilance Task

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

   Registry description

   fMRI measurement of task blocked activation

6. Psychomotor Vigilance Task

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

   Registry description

   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.

7. Wechsler Memory Scale III, Logical Memory Subset

   Time frame · baseline, then 12 weeks ± 3 days

   Registry description

   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.

8. Mini-Mental State Exam (MMSE)

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

   Registry description

   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.

9. CLOX: An Executive Clock Drawing Test

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

   Registry description

   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