A Pilot, Multiple Crossover, Randomized Block Sequence, Double-Blind, Placebo-Controlled Trial for Use of Methylphenidate for Cognitive and Behavioral Symptoms in Mild Cognitive Impairment and Dementia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.
研究概览
简要总结
Investigators are doing this research study to find out if methylphenidate (MPH) can help people with Mild Cognitive Impairment (MCI) or mild dementia likely due to Alzheimer's Disease (AD) and related disorders (ADRD).
The study drug MPH is approved by the U.S. Food and Drug Administration (FDA) to treat Attention Deficit/Hyperactivity Disorder (ADHD), but MPH is not approved by the FDA to treat Mild Cognitive Impairment or mild dementia related to Alzheimer's Disease. However, other studies have been done in which MPH has been given to people with neurodegenerative dementias and results have shown some improvement in these people's mood and cognition. Investigators would like to see if MPH will help mood and cognition.
This study will take place completely virtually (with the option to come in for the first visit to meet the study team). All study visits will occur over a secure videoconferencing platform. All study materials will be shipped directly to the home of each participant.
详细描述
Investigators will give participants a supply of study drug. Participants will take the study drug by mouth once a day for 16 weeks. It is important for participants to follow our instructions about how to take the study drug. Participants can take the drug with or without food. Investigators will provide enough study drug for participants to take until the next visit.
For this study, there are 3 blocks: each month-long block will consist of MPH for a two-week period (I.e. "A" Blocks 1, 2, 3) and PBO for a two-week period (I.e. "B" Blocks 1, 2, 3) in random assignment order for each block. Thus, all volunteers will receive a four-week PBO-lead in and acclimatization followed by treatment with MPH or matching PBO for eight-weeks each in three randomized sequence crossover blocks for a total of 10 weeks of PBO and 6 weeks of MPH.
Weekly Tasks During the study, certain tasks must be done each week.
Every Day:
The following tasks must be done each day throughout the study:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study subjects meeting all of the following criteria will be allowed to enroll in the study:
- •Aged 55-95 inclusive;
- •Diagnosis of MCI or mild-stage dementia presumed due to AD and AD-related disorders;
- •Cognitive abilities sufficient to be able to complete all study tasks as determined by the PI or a Co-I;
- •Education level, English language skills, and literacy that indicates participant will be able to comprehend all assessments;
- •Neuropsychiatric Inventory Agitation/Aggression Question 4 = "No" or "Yes" with a mild severity rating.
- •Willing and able to complete all assessments and study procedures;
- •Not pregnant, lactating, or of child-bearing potential
- •Volunteer has a Study Partner with at least two days per week of contact and willing to complete partner study forms;
- •No exclusionary medications or dietary supplements. See Section 6.5.8.1
- •If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline.
- •Basic video conferencing capabilities and a willingness to participate in a virtual trial (including self-administration of ECG).
排除标准
- •Subjects meeting any of the following criteria during the screening evaluation will be excluded:
- •Any history of specific CNS disease other than AD or AD-related disorders, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological or cognitive deficits or complaints;
- •Clinically significant or unstable medical condition that could affect safety or compliance with the study and would, in the opinion of the investigator, pose a risk to the participant if they were to participate in the study;
- •Major active or chronic psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year;
- •Current suicidal ideation or history of suicide attempt;
- •History of alcohol or other substance abuse or dependence with the past two years;
- •Clinically significant abnormalities on complete blood count, comprehensive metabolic panel, B12, or TSH screening safety lab results;
- •Concomitant use of medications with psychoactive properties that may deleteriously affect cognition (anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics);
- •Treatment with monoamine oxidase inhibitors, coumadin, phenobarbital, phenytoin, primidone, tricyclic antidepressants or other medicines with potential for clinically significant interaction;
- •Hypersensitivity to MPH;
- •History of marked anxiety and agitation, ADHD, motor tics, glaucoma, or a history or family history of Tourette's Syndrome;
- •Clinically significant cardiac condition for which MPH may be contradicted as determined by study physician, such as MI or ventricular arrhythmia within 6 months of enrollment;
- •History of untreated, uncontrolled hypertension or a blood pressure greater than 150/90 during the screening period;
- •Use of other small molecule or device- based investigational agents one month prior to entry and for the duration of the trial.
研究组 & 干预措施
Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
干预措施: Methylphenidate Extended Release Oral Capsule (Drug)
Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
干预措施: Placebo (Other)
Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
干预措施: Methylphenidate Extended Release Oral Capsule (Drug)
Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
干预措施: Placebo (Other)
Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
干预措施: Methylphenidate Extended Release Oral Capsule (Drug)
Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
干预措施: Placebo (Other)
Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
干预措施: Methylphenidate Extended Release Oral Capsule (Drug)
Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
干预措施: Placebo (Other)
Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
干预措施: Methylphenidate Extended Release Oral Capsule (Drug)
Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
干预措施: Placebo (Other)
Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
干预措施: Methylphenidate Extended Release Oral Capsule (Drug)
Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.
时间窗: 4 months
To assess feasibility of this study design, completion rates of all study tasks and medication dosing will be evaluated. Benchmark goals for feasibility measures are set as follows: retain \>80% of participants enrolled, observe \>80% medication adherence, and \>80% outcome assessment completion rates.
次要结局
- Cognition as Measured by the Repeatable Battery for the Assessment Neuropsychological Status-Update (RBANS)(4 months)
- Activity Level as Measured by Fitbit During MPH/PBO Blocks(4 months)
- Cognition as Measured by Daily, Home-based Brain Games (Lumosity, Lumos Labs, Inc.)(4 months)
- Sleep as Measured by Fitbit Charge 3(4 months)
研究者
Steven E Arnold, MD
Managing Director Physician
Massachusetts General Hospital