A Pilot of Methylphenidate in Mild Cognitive Impairment and Dementia Participants.

NCT03811847 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2018P003099
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Dementia

Outcome Measures

Primary Outcomes (1)

• Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.

  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.

  4 months

Secondary Outcomes (4)

• Cognition as Measured by the Repeatable Battery for the Assessment Neuropsychological Status-Update (RBANS)

  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

• Activity Level as Measured by Fitbit During MPH/PBO Blocks

  4 months

Study Arms (6)

Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH

EXPERIMENTAL

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.

Drug: Methylphenidate Extended Release Oral Capsule; Other: Placebo

Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO

EXPERIMENTAL

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.

Drug: Methylphenidate Extended Release Oral Capsule; Other: Placebo

Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH

EXPERIMENTAL

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.

Drug: Methylphenidate Extended Release Oral Capsule; Other: Placebo

Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO

EXPERIMENTAL

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.

Drug: Methylphenidate Extended Release Oral Capsule; Other: Placebo

Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH

EXPERIMENTAL

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.

Drug: Methylphenidate Extended Release Oral Capsule; Other: Placebo

Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO

EXPERIMENTAL

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.

Drug: Methylphenidate Extended Release Oral Capsule; Other: Placebo

Interventions

Methylphenidate Extended Release Oral Capsule DRUG

Stimulant It can treat ADHD and narcolepsy. 1 capsule 18mg

Also known as: Ritalin

Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH; Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO; Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH; Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO; Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH; Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO

Placebo OTHER

Placebo comparator MPH Matched Placebo Tablet

Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH; Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO; Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH; Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO; Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH; Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO

Eligibility Criteria

• Age: 55 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital, Clinical Translational Research Unit

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (1)

• DesRuisseaux LA, Williams VJ, McManus AJ, Gupta AS, Carlyle BC, Azami H, Gerber JA, Bolling AM, Cook CL, Betensky RA, Arnold SE. A pilot protocol to assess the feasibility of a virtual multiple crossover, randomized controlled trial design using methylphenidate in mild cognitive impairment. Trials. 2020 Dec 11;21(1):1016. doi: 10.1186/s13063-020-04752-x.

  PMID: 33308285 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Steven Arnold, MD
• Organization: Massachusetts General Hospital

searnold@mgh.harvard.edu

617-643-5607

Study Officials

• Steven E Arnold, MD

  MGH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Managing Director Physician

Model Details: The study uses a double-blinded, multi-crossover, randomized controlled trial design. This type of trial design in AD allow for each subject to serve as their own control as they progress through several randomized blocks of experimental treatment and placebo. Thus, multi-crossover studies carried out with systemically applied outcome measures, pre-specified doses of study drug, and washout periods serve as unbiased estimates of treatment effect for individual subjects. When data from several subjects are analyzed together following such a N-of-1 design, substantial increases in statistical power is afforded with a fraction of the subjects and assessments required for similar levels of power in conventional parallel group trials. There are 6 different block randomization sequences for which subjects were assigned.

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 22, 2019
• Study Start: November 1, 2019
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: June 2, 2023
• Results First Posted: June 2, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)