Cognitive and Functional Connectivity Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 入组人数
- 117
- 试验地点
- 1
- 主要终点
- fMRI Measurement
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Pregnancy or breastfeeding
- •Contraindication for MRI (Claustrophobia and magnetic metal implants)
- •Glucose-6-phosphate deficiency, methemoglobinemia
- •Allergy to MB
- •Color-blindness
- •Craniotomy, craniectomy or endovascular neurosurgery
- •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)
- •A serious intercurrent illness likely to cause death within the next 5 years, such as terminal cancer
- •Alcohol and/or drug abuse
- •Any detection of an unknown disease process (eg. new tumor) on the study's neuroimaging at the discretion of the investigators
- •A systolic blood pressure ≥180 mmHg and/or a diastolic blood pressure ≥105 mmHg
- •Severe difficulty or an inability to perform any one of the 6 Katz Activities of Daily Living
- •Patients who are unlikely to comply with trial visit schedule or with trial medication,
- •On any psychiatric serotonergic antidepressant medication or psychotropic medication within the last 5 weeks
- •Diagnosis of epilepsy, traumatic brain injury with loss of consciousness, psychosis, panic attacks,
- •Chronic kidney disease, cirrhosis, liver or renal transplants
- •Known hypersensitivity to thiazide diuretics and phenothiazines
- •Any other condition, which in the opinion of the investigator, would put the participant at risk and warrant exclusion from the study
研究组 & 干预措施
Healthy Aging MB
Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks)
干预措施: Methylene Blue (Drug)
Healthy Aging MB
Methylene Blue (USP grade, 282mg oral, daily, 2 weeks, 12 weeks) Phenazopyridine hydrochloride (97.5 mg oral, 2 weeks, 12 weeks)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: FD&C Blue # 2 (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: Methylene Blue (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: FD&C Blue # 2 (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: Methylene Blue (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: FD&C Blue # 2 (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: Methylene Blue (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
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)
干预措施: FD&C Blue # 2 (Drug)
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)
干预措施: Phenazopyridine hydrochloride (Drug)
结局指标
主要结局
fMRI Measurement
时间窗: baseline, 2 weeks and 12 weeks
fMRI measurement of task blocked activation during Wechsler Memory Scale III
Wechsler Memory Scale, Third Edition
时间窗: baseline, 2 weeks ± 3 days, 12 weeks ± 3 days
Working memory task behavioral measures (ie. correct number of responses) Score is 0-104, with higher scores being better.
fMRI During FNAME
时间窗: baseline, 2 weeks ± 3 days,12 weeks ± 3 days
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.
FNAME
时间窗: baseline, 2 weeks ± 3 days,12 weeks ± 3 days
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
fMRI During Psychomotor Vigilance Task
时间窗: baseline,2 weeks ± 3 days,12 weeks ± 3 days
fMRI measurement of task blocked activation
Psychomotor Vigilance Task
时间窗: 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). 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.
Wechsler Memory Scale III, Logical Memory Subset
时间窗: baseline, then 12 weeks ± 3 days
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.
Mini-Mental State Exam (MMSE)
时间窗: baseline, 2 weeks ± 3 days,12 weeks ± 3 days
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.
CLOX: An Executive Clock Drawing Test
时间窗: baseline, 2 weeks ± 3 days, 12 weeks ± 3 days
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
次要结局
- Cerebral Blood Flow Measures(baseline, 2 weeks ± 3 days, 12 weeks ± 3 days)