Individualized Cognitive Training in HIV (TOPS)

October 17, 2021 updated by: David Vance, PhD, University of Alabama at Birmingham

Individualized-Targeted Cognitive Training in Older Adults With HAND

Over 50% of adults with HIV have some form of HIV-Associated Neurocognitive Disorder (HAND) which represents a significant symptom that interferes with everyday functioning and quality of life. As adults age with HIV, they are more likely to develop comorbidities such as cardiovascular disease, hypertension, and insulin resistance which will further contribute to poorer cognitive functioning and HAND. Based upon the Frascati criteria, HAND is diagnosed when a person performs less than 1 to 2 SD below their normative mean (education & age) on measures of two or more cognitive domains (e.g., attention, speed of processing, verbal memory, executive functioning). Yet, from the cognitive literature and prior studies, administering certain computerized cognitive training programs may improve specific cognitive domains in older adults and those with HIV. Such cognitive training programs may be effective in older adults with HIV and therefore investigators may be able to change the diagnosis of HAND in such cognitively vulnerable adults. In this pre-post experimental study, 146 older adults (50+) with HAND will be randomized to be in either: 1) the Individualied-Targeted Cognitive Training, or 2) a no-contact control group. The investigators will focus on those cognitive domains in which participants express an impairment and train them with the corresponding cognitive program. Such an Individualized-Targeted Cognitive Training approach using standard cognitive training programs may offer hope and symptom relief to those individuals diagnosed with HAND. Furthermore, these changes may result in improved everyday functioning (e.g., IADLs) and quality of life. This approach represents a paradigm shift in possibly changing the way HAND is examined. Specific Aim 1: Compare adults who do receive Individualized-Targeted Cognitive Training to those who do not in order to determine whether a change in HAND prevalence and severity occurs between groups. Exploratory Aim 1: Compare adults who do receive individualized-targeted cognitive training to those who do not in order to determine whether this improves everyday functioning (e.g., IADLs). Exploratory Aim 2: Determine whether improvements in HAND and/or everyday functioning over time mediate improvements in quality of life.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This research directly meets the goals of the NIH Cognitive and Emotional Health Project and the Healthy Brain Initiative which seek to "maintain or improve the cognitive performance of all adults," especially for "populations experiencing the greatest disparities and risks in cognitive health."

Significance: Using the Frascati criteria, 52% - 59% of people with HIV experience some form of HIV-Associated Neurocognitive Disorder (HAND) which affects medication adherence, instrumental activities of daily living (IADLs), and even mood maintenance and quality of life. By 2020, 70% of adults with HIV in the United States will be 50 and older; thus, cognitive aging in this group represents a major concern. In a prior study (R03MH076642-01A2) conducted in the HAART era, when comparing cognitive functioning between older and younger HIV-positive and HIV-negative adults, older adults with HIV performed the worst. In the HAART era, these cognitive impairments continue to be observed in several cognitive domains including memory, learning, executive functioning, and speed of processing.

Regrettably, few behavioral interventions aimed at improving cognition in this pharmacologically-burdened population have been attempted. Pharmacological interventions have short-lived effects, if any, and can produce adverse side effects in a population prone to multiple comorbidities. Fortunately, computerized cognitive training interventions have been shown to improve cognition without adverse side-effects. Yet, only two types of computerized cognitive training interventions have been studied in adults with HIV. Becker and colleagues partially randomized 60 adults with HIV and without HIV to engage in 14 computerized targeted modules (e.g., knowledge, memory) over 24 weeks. No significant effects were found; however, adherence was poor. In a prior study, investigators randomized 46 adults to either a speed of processing training (10 hrs of training) group or a no-contact control group. Adherence was excellent and improvements were observed on this cognitive domain which transferred to an everyday functioning task.

Despite this lack of cognitive training studies in HIV, studies in older adults have shown their efficacy in improving specific cognitive abilities, some as much as 1-1.5 standard deviations (SD) above baseline performance or age/education-based norms. Using Frascati criteria, HAND is diagnosed when a person performs at least 1 to 2 SD below their normative mean on measures of two or more cognitive domains (e.g., verbal memory, speed of processing, executive functioning); yet many individuals may be only a fraction of a SD below the cut off. A meta-analysis of 52 cognitive training studies indicated the average cognitive improvement following cognitive training was 0.22 SD. Although this seems to be a small to moderate effect size, such cognitive training programs can change the diagnosis of HAND for some by improving cognitive performance to within acceptable performance norms. In this study, older adults (50+) with HAND will be enrolled to determine which cognitive domains are attributable to their diagnosis. Then those cognitive domains in which they have impairments will be targeted for training with the corresponding cognitive program. Such a tailored approach to standard cognitive training programs may offer hope and symptom relief to those individuals diagnosed with HAND. Furthermore, these changes may result in improved everyday functioning and quality of life. This approach also represents a paradigm shift in changing the way clinicians and researchers look at HAND in that this is not a static "progressive" diagnosis; Antinori et al. observed a 20% fluctuation of HAND over as little as 1 year, with some improving or declining in their cognitive performance. Such fluctuations, at least partially, reflect positive neuroplasticity that can be manipulated with cognitive training to improve cognition which can improve medication adherence and other IADLs. This study will use a basic two group pre-post experimental design of 146 adults with HAND.

Study Type

Interventional

Enrollment (Actual)

109

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 Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35222
        • University of Alabama at Birmingham

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

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must be 40+ years
  • English speaking
  • Have HIV-Associated Neurocognitive Disorder (HAND)

Exclusion Criteria:

  • Because the study requires several weeks, participants not living in stable housing (e.g., halfway house) will be excluded.
  • Participants with significant neuromedical co-morbidities (e.g., schizophrenia, epilepsy, bipolar disorder, multiple sclerosis, Alzheimer's disease or related dementias, mental retardation)
  • Currently undergoing radiation or chemotherapy
  • A history of brain trauma with a loss of consciousness greater than 30 minutes
  • Legally blind or deaf

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Individualized Cognitive Training
Participants randomized to this arm will receive 20 hours of computerized cognitive training in the two predominate cognitive domains in which they experience deficits that contribute to their HIV-Associated Neurocognitive Disorder diagnosis.
Behavioral: Individualized Cognitive Training
These are specific computerized exercises that are designed to improve performance in particular cognitive domains (e.g., attention, speed of processing, verbal learning/memory).
Other Names:
  • Insight Software
Other: No-Contact Control
Participants in this arm will not receive any experimental or sham contact. They will only participate in the Baseline and Posttest assessments.
Other: No-Contact Control
This is simply a no-contact control group. Participants in this group will receive no additional contact with the study beyond the baseline and posttest assessments.
Other Names:
  • Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence and Severity of HIV-Associated Neurocognitive Disorder (HAND) as Measured by Neurocognitive Tests Interpreted by the Frascati Criteria
Time Frame: Per participants, approximately 10-12 weeks
Compare adults who do receive Individualized-Targeted Cognitive Training to those who do not in order to determine whether a change in HAND prevalence and severity occurs between groups. A battery of neurocognitive tests (e.g., Trails Making Test A, Trails Making Test B, etc.) of different domains (e.g., speed of processing, verbal memory, etc.) are used which are normed by age/education which are then use with the Frascati Criteria (a neurological algorithm to classify cognitive impairment) to determine HIV-Associated Neurocognitive Disorder, both presence and severity (i.e., Global Severity Rating). This is administered at baseline and posttest.
Per participants, approximately 10-12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement on Everyday Functioning as Measured by the Timed Instrumental Activities of Daily Living Test
Time Frame: Per participants, approximately 10-12 weeks
The Timed Instrumental Activities of Daily Living Test -- This test measures the accuracy and time it takes to perform 5 IADLs (e.g., counting out correct change, reading ingredients on a can of food). Slower speed of processing is associated with longer times to complete these tasks, even after adjusting for age, education level, depression, and general health. The time from each of the 5 IADLs is added together to form a composite score. Test-retest reliability is 0.64. This test is administered at baseline and posttest.
Per participants, approximately 10-12 weeks
Improvement on Everyday Functioning as Measured by the Medication Adherence Scale
Time Frame: Per participants, approximately 10-12 weeks
Medication Adherence - This IADL is measured by the Simplified Medication Adherence Questionnaire (as well as virological control). It consists of sixl items that ask about how consistently one takes his/her medications; the items can be summed to form a composite score. This measure is validated with virological outcomes and has good internal consistency (α = 0.75) and inter-observer agreement (88.2%). This questionnaire is administered at baseline and posttest.
Per participants, approximately 10-12 weeks
Improvement in Quality of Life as Measured by Depression
Time Frame: Per participants, approximately 10-12 weeks
Centers for Epidemiological Studies - Depression Scale (CES-D) - This depression scale measures how often (not at all - extremely) participants acknowledge 20 verbal symptoms of depression; score are tallied to form a composite score; higher scores indicate greater self-reported depressive symptomatology. Cronbach's α is very good at 0.88. This scale is administered at baseline and posttest.
Per participants, approximately 10-12 weeks
Improvement in Quality of Life as Measured by Internal Locus of Control
Time Frame: Per participants, approximately 10-12 weeks
Internal Locus of Control - This six (6-point Likert-type) item measure assesses the degree to which participants perceive that they can exert influence over their life. The items are summed to form a composite score; higher scores indicate more internal locus of control. Cronbach's α's range from 0.62 to 0.79. This measure is administered at baseline and posttest.
Per participants, approximately 10-12 weeks
Improvement in Quality of Life as Measured by Health-Related Quality of Life
Time Frame: Per participants, approximately 10-12 weeks
Medical Outcomes Study Short Form (SF-36)/Health-Related Quality of Life - SF-36 assesses health-related quality of life which is a subscale of this measure. The item of this subscale are summed to form a composite score. In the ACTIVE Study, improvement on this variable was observed in the speed of processing training group. Cronbach's α is greater than 0.85. This subscale is administered at baseline and posttest.
Per participants, approximately 10-12 weeks
Improvement in Quality of Life as Measured by Self-Rated Health
Time Frame: Per participants, approximately 10-12 weeks
Medical Outcomes Study Short Form (SF-36)/Self-Rated Health - SF-36 assesses self-rated health on only 1 item which is a Likert type scale (In general, I would say that my health is: Excellent, Very Good, Good, Fair, Poor). In the ACTIVE Study, improvement on self-rated health was observed in the speed of processing training group. This item is administered at baseline and posttest.
Per participants, approximately 10-12 weeks
Improvement in Quality of Life as Measured by Cognitive Complaints
Time Frame: Per participants, approximately 10-12 weeks
Cognitive Failures Questionnaire (CFQ) - CFQ assesses common everyday cognitive complaints one may have such as in memory (e.g., "Do you forget where you put something like a newspaper or book?"). All of the 25 items on this measure are summed to form an overall composite score; higher scores are indicative of greater subjective cognitive complaints. This questionnaire is administered at baseline and posttest.
Per participants, approximately 10-12 weeks

Collaborators and Investigators

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

Sponsor

University of Alabama at Birmingham

Collaborators

National Institute of Nursing Research (NINR)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

July 27, 2017

Primary Completion (Actual)

February 27, 2019

Study Completion (Actual)

February 27, 2019

Study Registration Dates

First Submitted

April 11, 2017

First Submitted That Met QC Criteria

April 19, 2017

First Posted (Actual)

April 20, 2017

Study Record Updates

Last Update Posted (Actual)

October 19, 2021

Last Update Submitted That Met QC Criteria

October 17, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • F161122002
  • 1R21NR016632-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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.

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