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

Dementia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04171323
• Other study ID #: WIRB® Protocol #20192632
• Secondary ID: R01AG075014
• Status: Recruiting
• Phase: N/A
• Start date: March 3, 2020
• Est. completion date: August 31, 2027

Study information

• Verified date: November 2023
• Source: University of South Florida
• Contact: Jerri Edwards, PhD
• Phone: 813.974.6703
• Email: usfcognitiveagelab[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1305
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Age-related Cognitive Decline
• Cognitive Dysfunction
• Dementia
• Mild Cognitive Impairment

Intervention

Behavioral:
• Cognitive Training
Participants will be completing a total of 40 computerized sessions.
• Computerized Cognitive Stimulation
Participants will be completing a total of 40 computerized cognitive stimulation sessions.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of California San Francisco	San Francisco	California
United States	Clemson University	Seneca	South Carolina
United States	University of South Florida	Tampa	Florida

Sponsors (6)

Lead Sponsor	Collaborator
University of South Florida	Clemson University, National Institute on Aging (NIA), University of California, San Francisco, University of Florida, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	blood based biomarker Neurofilament light (Nfl)	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
Other	blood based biomarker Total tau	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
Other	blood based biomarker hydroxsphingomyelins SM (OH) C22:1, SM (OH) C22:2, SM (OH) C24:1	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
Other	blood based biomarker brain derived neurotropic factor (BDNF)	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
Other	blood based biomarker insulin growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP1) and IGFBP-2	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
Other	blood based vascular biomarkers of asymmetric dimethylarginine [ADMA]; aspartic avid; acetyl-L-cartinine [C2]; butenyl-L-cartinine [C4:1]	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
Other	Neuroimaging MRI whole brain and regional volume	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
Other	Neuroimaging MRI surface area cortical thickness metrics from T1 weighted images	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
Other	Neuroimaging MRI whole brain and regional white matter hyper-intensity volume from FLAIR	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
Other	Neuroimaging MRI hippocampal subfield volume from high resolution hippocampal images	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
Other	Neuroimaging MRI regional and white matter metrics of fractional anisotropy from diffusion weighted imaging	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
Other	Neuroimaging MRI regional and white matter metrics of median diffusivity from diffusion weighted imaging	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
Other	Neuroimaging MRI regional and white matter metrics of radial diffusivity from diffusion weighted imaging	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
Other	Neuroimaging MRI regional and whole brain measures of cerebral perfusion from arterial spin labeling	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
Other	Neuroimaging MRI regional and whole brain cerebral microbleed volume from T2*GRE images	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
Other	Neuroimaging regional and network measures of functional connectivity for resting state fMRI	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
Other	Virtual Reality Functional Assessment Tool performance	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
Primary	Dementia incidence	Clinical diagnosis of dementia	At follow-up visit between 6 months to 2 years
Secondary	Useful Field of View Test performance overall score	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
Secondary	Graduated continuous performance test score	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
Secondary	Examiner Executive Function Set shifting, Anti-Saccades, and Flanker performance composite score	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
Secondary	Timed IADL performance score	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
Secondary	ifunction performance efficiency index	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