The Active Mind Trial: An Adaptive Randomized Trial to Improve Function and Delay Dementia

November 28, 2023 updated by: Jerri D. Edwards, University of South Florida

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

1305

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • California
      • San Francisco, California, United States, 94158
        • Recruiting
        • University of California San Francisco
        • Principal Investigator:
          • Joel Kramer, PhD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32611
        • Recruiting
        • University of Florida
        • Contact:
          • Andrew O'Shea
        • Principal Investigator:
          • Adam Woods, PhD
        • Sub-Investigator:
          • Sam Wu, PhD
        • Sub-Investigator:
          • Glenn Smith, PhD
        • Sub-Investigator:
          • Steve DeKosky, MD
      • Tampa, Florida, United States, 33620
        • Recruiting
        • University of South Florida
        • Principal Investigator:
          • Jerri Edwards, PhD
        • Contact:
          • Cognitive Aging Lab
          • Phone Number: 813-974-6703
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Active, not recruiting
        • University of Minnesota
    • South Carolina
      • Seneca, South Carolina, United States, 29672
        • Recruiting
        • Clemson University
        • Principal Investigator:
          • Lesley A Ross, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CTa
Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions.
Participants will be completing a total of 40 computerized sessions.
Experimental: CTab
Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions.
Participants will be completing a total of 40 computerized sessions.
Experimental: CTac
Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions.
Participants will be completing a total of 40 computerized sessions.
Experimental: CTabc
Participants will complete computerized cognitive training. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions.
Participants will be completing a total of 40 computerized sessions.
Active Comparator: Computerized Cognitive Stimulation
Participants will complete cognitively-stimulating computer activities. The duration is 60 min/day; the frequency is two to three days/wk, for 16 weeks with the goal of completing 40 sessions.
Participants will be completing a total of 40 computerized cognitive stimulation sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dementia incidence
Time Frame: At follow-up visit between 6 months to 2 years
Clinical diagnosis of dementia
At follow-up visit between 6 months to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Timed IADL performance score
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
A composite z score is calculated that reflects the overall time and accuracy of performance on the Timed IADL subtests per standard, published procedures (SPSS syntax of scoring method can be provided). Lower scores are better.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
ifunction performance efficiency index
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
An overall score reflecting time and accuracy (i.e., efficiency index) is calculated to reflect performance across the ifunction subtests the proprietary software determines the score. Higher scores are better for efficiency index
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Useful Field of View Test performance overall score
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Useful Field of View test (UFOV) score across three subtests measured in milliseconds (ms). Lower scores are better.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Graduated continuous performance test score
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
The metrics of performance are target accuracy (in percent correct) and the variability of responses (standard deviation of response times to target images). Higher scores are better.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Examiner Executive Function Set shifting, Anti-Saccades, and Flanker performance composite score
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
The proprietary software calculates an overall executive function composite score using item response theory. Higher scores are better
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
blood based biomarker Neurofilament light (Nfl)
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
blood based biomarker Total tau
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrast
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
blood based biomarker hydroxsphingomyelins SM (OH) C22:1, SM (OH) C22:2, SM (OH) C24:1
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
blood based biomarker brain derived neurotropic factor (BDNF)
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
blood based biomarker insulin growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP1) and IGFBP-2
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
blood based vascular biomarkers of asymmetric dimethylarginine [ADMA]; aspartic avid; acetyl-L-cartinine [C2]; butenyl-L-cartinine [C4:1]
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI whole brain and regional volume
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI surface area cortical thickness metrics from T1 weighted images
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI whole brain and regional white matter hyper-intensity volume from FLAIR
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI hippocampal subfield volume from high resolution hippocampal images
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI regional and white matter metrics of fractional anisotropy from diffusion weighted imaging
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI regional and white matter metrics of median diffusivity from diffusion weighted imaging
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI regional and white matter metrics of radial diffusivity from diffusion weighted imaging
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI regional and whole brain measures of cerebral perfusion from arterial spin labeling
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging MRI regional and whole brain cerebral microbleed volume from T2*GRE images
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Neuroimaging regional and network measures of functional connectivity for resting state fMRI
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Virtual Reality Functional Assessment Tool performance
Time Frame: change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months
Measures may include Virtual Reality Functional Assessment Tool (VRFCAT) Effect sizes of between group differences will be calculated using linear contrasts.
change from baseline to immediate post intervention at the end of study completion which is a period of about 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jerri Edwards, PhD, University of South Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2020

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

August 31, 2027

Study Registration Dates

First Submitted

November 7, 2019

First Submitted That Met QC Criteria

November 19, 2019

First Posted (Actual)

November 20, 2019

Study Record Updates

Last Update Posted (Actual)

December 5, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • WIRB® Protocol #20192632
  • R01AG075014 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dementia

Clinical Trials on Cognitive Training

3
Subscribe