Clinical trial NCT04171323: The Active Mind Trial: An Adaptive Randomized Trial to Improve Function and Delay Dementia
Official title: ACTIVE MIND: An Adaptive Clinical Trial of Cognitive Training to Improve Function and Delay Dementia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Age-related Cognitive Decline
Mild Cognitive Impairment
Dementia
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: University of Florida
name: University of Minnesota
name: National Institute on Aging (NIA)
name: Clemson University
name: University of California, San Francisco
First posted: 2019-11-20
Enrollment: 1305
Sex: ALL
Minimum age (years): 55
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Older adults at risk for dementia show a variety of cognitive deficits, which can be ameliorated by different cognitive training (CT) exercises. The best combination of CT exercises is unknown. The aim is to discover the most efficacious combination of CT exercises as compared to cognitive stimulation (which will serve as a stringent, active control) to modify the functional trajectories of older adults' with MCI, who are at high risk for dementia. The primary objective of the U01 phase was to design and pilot-test an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). In the R01 phase, the objective is to identify the best combination of CT exercises to delay dementia onset among persons with MCI. The longitudinal endpoint goal is reducing incident dementia. The primary aim of the study is to determine which CT combination has the best probability to delay dementia by producing the largest IADL improvements. The study further aims to explore neuroimaging and novel blood-based biomarkers.

Detailed description: An Adaptive Clinical Trial of Cognitive Training to Improve Function and Delay Dementia: The ACTIVE MIND Trial.

In the U01 phase, the primary objective was to design and pilot-test an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). The longitudinal endpoint goal is delaying dementia onset.

The secondary objectives of the U01 phase were:

- To pilot test a plan to recruit and enroll under-represented minorities with the goal of obtaining a sample representative of the USF population in race and ethnicity.

In the current R01 phase:

The primary objective is to conduct an adaptive, randomized clinical trial (RCT) of cognitive training (CT) combinations aimed to enhance performance of instrumental activities of daily living (IADL) among persons with mild cognitive impairment (MCI). The longitudinal endpoint goal is reducing dementia incidence.

Design: The design is an adaptive randomized trial to identify the best combination of CT exercises to improve IADL function and thereby delay dementia onset among persons with MCI. Four arms of CT will be compared to an active control condition.

Outcomes: incident dementia is the primary outcome. Secondary outcome is Everyday Function: measures include Timed Instrumental Activities of Daily Living and iFunction. A composite of performance (measured by time and accuracy) will be derived.

Interventions and Duration: Four combinations of computerized cognitive training and an active control computerized stimulation will be investigated. The five arms will be equivalent in terms of frequency and duration of each session (60 min/day, two-three days/wk, 16 weeks).

Sample size: The study team plans to enroll up to 1305 participants. Individuals with a clinical diagnosis of MCI will be included in the study.

Eligibility criteria: Inclusion Criteria:

* 55 to 89 years of age
* Montreal Cognitive Assessment Score of 18-27 inclusive
* History of some change in cognitive function relative to established baseline and either 1) a CDR of 0.5; or 2) CDR of 0 and a clinical diagnosis of mild cognitive impairment (MCI) based on a multidisciplinary evaluation that included standardized neuropsychological testing
* If reports use of medications typically prescribed for dementia such as Namenda, Memantine, Namzaric, Donepezil, Aricept, Rivastigmine, Exelon, Razadyne, Galantamine, or Reminyl, dose has been stable for at least 30 days
* Adequate auditory capacity to understand normal speech. No greater than moderate hearing loss evident by thresholds less than or equal to 50 dB at 1000 and 2000 Hz in at least one ear determined by an audioscope.
* Adequate visual capacity to read from a computer screen at a normal viewing distance as measured by binocular visual acuity of 20/50 or better tested with a standard near visual acuity chart
* Reports and shows adequate motor capacity to touch a computer screen or control a computer mouse.
* Wiling to complete all study activities
* Willing and capable of providing informed consent
* Ability to understand study procedures and comply with them for the length of the study

Exclusion Criteria:

* Currently enrolled in another randomized clinical trial, treatment trial, or another research study that assesses cognition
* Dementia diagnosis
* Clinical Dementia Rating Scale of 1 or greater
* History of large vessel stroke with significant residual motor or cognitive impairment
* History of moderate to severe traumatic brain injury with residual cognitive symptoms
* History of brain tumor
* Undergoing or plans to undergo surgery requiring anesthesia, chemotherapy, or radiation treatment in the six months following screening
* Congestive heart failure diagnosis
* Primary diagnosis of idiopathic Parkinson's disease
* Multiple sclerosis or Amyotrophic lateral sclerosis (ALS) diagnosis
* Evidence of a non-neurodegenerative neurological disorder that would interfere with the ability to carry out study activities.
* Evidence of any other unstable medical conditions that would interfere with the ability to carry out study activities or cause fluctuations in cognition (e.g., unstable diabetes, chronic obstructive pulmonary disorder dependent on oxygen)
* Geriatric Depression short scale score \>5/15. Participants with mood disorders that are treated and stable and have a GDS score \< 6/15 are not excluded.
* Any other clinically significant or unstable medical condition (e.g., ongoing alcohol dependency or drug abuse, schizophrenia, psychosis) that in the assessor's opinion would interfere with the ability to carry out study activities.
* Previous participation in 10 or more hours of a computerized cognitive intervention program in the past two years
* Previous participation in cognitive intervention research at the study site in the past 2 years
* Planning on going away or being otherwise unavailable for a period of more than three weeks in the six months following screening
* Contraindications to MRI such as pacemaker, metal implants in body, or claustrophobia

Primary outcomes:
measure: Dementia incidence
timeFrame: At follow-up visit between 6 months to 2 years
Secondary outcomes:
measure: Useful Field of View Test performance overall score
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Graduated continuous performance test score
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Examiner Executive Function Set shifting, Anti-Saccades, and Flanker performance composite score
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Timed IADL performance score
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: ifunction performance efficiency index
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Other outcomes:
measure: blood based biomarker Neurofilament light (Nfl)
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: blood based biomarker Total tau
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: blood based biomarker hydroxsphingomyelins SM (OH) C22:1, SM (OH) C22:2, SM (OH) C24:1
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: blood based biomarker brain derived neurotropic factor (BDNF)
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: blood based biomarker insulin growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP1) and IGFBP-2
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: blood based vascular biomarkers of asymmetric dimethylarginine [ADMA]; aspartic avid; acetyl-L-cartinine [C2]; butenyl-L-cartinine [C4:1]
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI whole brain and regional volume
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI surface area cortical thickness metrics from T1 weighted images
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI whole brain and regional white matter hyper-intensity volume from FLAIR
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI hippocampal subfield volume from high resolution hippocampal images
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI regional and white matter metrics of fractional anisotropy from diffusion weighted imaging
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI regional and white matter metrics of median diffusivity from diffusion weighted imaging
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI regional and white matter metrics of radial diffusivity from diffusion weighted imaging
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI regional and whole brain measures of cerebral perfusion from arterial spin labeling
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging MRI regional and whole brain cerebral microbleed volume from T2*GRE images
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Neuroimaging regional and network measures of functional connectivity for resting state fMRI
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
measure: Virtual Reality Functional Assessment Tool performance
timeFrame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Seneca
country: United States
facility: Clemson University
state: South Carolina
Study officials:
affiliation: University of Alabama at Birmingham
name: Jerri Edwards, PhD
role: PRINCIPAL_INVESTIGATOR
References: