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CompletedNCT03440840Updated Sep 18, 2023Results posted

Computer Training and Transcranial Direct Current Stimulation for Cognition in HIV

An interventional study of Transcranial Direct Current Stimulation (tDCS) and Computer-based Cognitive Training in HIV-related Mild Neurocognitive Disorder, sponsored by Nova Southeastern University. Completed at 1 site in United States. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2023-09-18.

Sponsored by Nova Southeastern University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study summary

This study investigates the effectiveness of computer-based cognitive training with or without transcranial direct current stimulation (tDCS) in improving the functioning of older individuals with HIV-related cognitive dysfunction.

Read the detailed description

In spite of advances in its treatment, persons with HIV continue to develop HIV-associated neurocognitive disorders (HAND) over time. HAND may be an even more significant problem in older persons (age 50+) with HIV who may experience age-related changes in cognition in addition to HAND. Because of HAND's impact on patients' functioning and quality of life, treatments are needed. Pharmacologic treatments have, in general, been ineffective and investigators have argued that computer delivered cognitive training may be an effective alternative. While results of small studies have been encouraging, the effect size of cognitive training may be small and of unclear practical importance. The nature of cognitive training programs, often building on laboratory measures of cognition, may reduce how inherently interesting (i.e., fun) they are, limiting their uptake outside of paid research studies. Others have argued for the use of computer games targeting psychomotor speed, problem solving, and visuospatial skills to improve cognitive function in older adults. Data support the utility of this approach, but again effect sizes may be small.

Transcranial direct current stimulation (tDCS) may be an effective way to enhance the effects of cognitive training. It involves the application of a small electric current (1-2 mA) to the head, inducing small currents within the brain that enhance cognitive training. Multiple studies have shown that tDCS enhances cognition, including attention and psychomotor speed. The investigators previously completed a single-blind pilot study of individuals with HIV-related mild neurocognitive disorder using a high-interest car racing game with or without tDCS. Results were encouraging in showing moderate to large effect sizes consistent with tDCS enhancement of cognitive function after six 20-minute training sessions over two weeks. Participants' subjective reports of cognitive difficulties supported observed effects on objective measures, and their mood improved. The intervention was acceptable to participants, many of whom stated they enjoyed it. Everyone indicated a willingness to participate in a similar study in the future.

In this study the investigators will expand on a pilot-tested training intervention with 120 individuals randomly assigned to an attention control condition or game-based cognitive training with either sham or active tDCS. The investigators will employ a battery of cognitive measures as well as self-report measures of mood, cognitive difficulties, and everyday functioning in order to evaluate the effects of study interventions.

Participants will first be screened for eligibility by telephone, and then scheduled for a visit during which their eligibility will be further assessed. Those who are eligible based on inclusion and exclusion criteria will complete a battery of measures of their cognitive and functional status. They will then complete six training sessions over a period of three weeks, and then once again complete the battery of assessments. Participants will then be asked to return one month after the post-training assessment to evaluate the persistence of training effects.

02

Conditions studied

  • HIV-related Mild Neurocognitive Disorder
03

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Treated with antiretroviral medication for at least one month
  • Meet criteria for Mild Neurocognitive Disorder

Exclusion criteria

Exclusion Criteria:

  • Seizure disorder
  • Recent head injury or surgery
  • Personal or family history of bipolar disorder;
  • Some medications
  • Left handedness
  • HIV Dementia
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    Computer Training with active tDCS

    Participants randomized to this arm will receive computer-based cognitive training using a car racing game with active transcranial direct current stimulation (tDCS).

    Procedure: Transcranial Direct Current Stimulation (tDCS) · Behavioral: Computer-based Cognitive Training

  • Active comparator
    Computer Training with sham tDCS

    Participants randomized to this arm will receive computer-based cognitive training using a car racing game with sham transcranial direct current stimulation (tDCS).

    Behavioral: Computer-based Cognitive Training

  • Placebo comparator
    Computer Training with or without tDCS

    Participants in this arm will watch educational videos as a comparator to computer training with the car racing game (watching educational videos).

    Procedure: Transcranial Direct Current Stimulation (tDCS) · Behavioral: Watching Educational Videos

Interventions

  • ProcedureTranscranial Direct Current Stimulation (tDCS)

    Application of a small electrical current (1-2 mA) across the head.

    Also known as: tDCS

  • BehavioralComputer-based Cognitive Training

    Use of computer-delivered games or exercises with the goal of improving cognitive performance.

    Also known as: Cognitive Training

  • BehavioralWatching Educational Videos

    Watching educational videos and answering questions about them

05

What researchers measure

Primary outcomes

  1. Psychomotor Speed

    Ability of the participant to attend to and use complex stimuli while making a motor response. The Coding subtest of the Wechsler Adult Intelligence Scale, 4th ed. (WAIS-IV) asks that the person assessed insert small geometric drawings with pencil on paper according to a key at the top of the page. One figure corresponds to the numeral 1, another to 2, and so on. The persons is asked to work as quickly as they can, and given a specific period in which to complete the task. Raw scores are the number of boxes correctly filled in during the time allowed and can range from 0 to 155, with higher scores indicating a better performance.

    Time frame: 3 weeks

Secondary outcomes

  1. Functional Status

    Participant performance on observed tasks of daily living. Participants completed the University of California--San Diego Performance Based Skills Assessment, version B. The person assessed is asked to complete several functional tasks, including pretending to make a call on a telephone to change a medical appointment and paying an electric bill by filling out a check. Scores on the first task range form 0 to 9, and from 0 to 11 on the second. These raw scores are then converted to create a final combined score that ranges from 0 to 100, with higher scores indicating a better performance.

    Time frame: 3 weeks

  2. Participant Assessment of Own Functioning (PAOF)

    Participant self-report of problems related to cognitive and sensory functioning on the Participant Assessment of Own Functioning (PAOF). This is a self-report measure of the frequency with which a person experiences difficulties with various mental and sensory tasks, such as remembering what is said to them, understanding or expressing themselves in language, and thinking about complex problems. The PAOF includes 33 items ranged from 0 to 5, allowing a total score from 0 to 165. A higher score on this measure means that the person is reporting greater frequency with some mental activities.

    Time frame: 3 weeks

  3. Center for Epidemiological Studies Depression Scale (CES-D)

    Participant self-report of mood. The Center for Epidemiological Studies Depression scale (CES-D) is a self-report measure of symptoms of and related to depressed mood. It includes 20 items that are scored from 0 to 3 and summed for an overall score ranging from 0 to 60. Higher scores on this measure indicate that the person assessed is reporting a greater frequency or severity of depressive symptoms.

    Time frame: 3 weeks

06

Results

Posted Sep 18, 2023
Limitations and caveats
In this trial, we were only able to recruit 46 participants, of whom 44 completed the study. The original plan was to recruit 120 individuals, of whom 90 would complete the study. The sample size is thus substantially smaller than planned.

Participant flow

Participant flow — Overall Study
MilestoneComputer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCS
Started161515
Completed151415
Not completed110

Outcome measures

PrimaryPsychomotor Speed

Ability of the participant to attend to and use complex stimuli while making a motor response. The Coding subtest of the Wechsler Adult Intelligence Scale, 4th ed. (WAIS-IV) asks that the person assessed insert small geometric drawings with pencil on paper according to a key at the top of the page. One figure corresponds to the numeral 1, another to 2, and so on. The persons is asked to work as quickly as they can, and given a specific period in which to complete the task. Raw scores are the number of boxes correctly filled in during the time allowed and can range from 0 to 155, with higher scores indicating a better performance.

Time frame:
3 weeks
Reported as:
Mean · score on a scale
Psychomotor Speed
score on a scaleComputer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCS
Psychomotor Speed54.2 (43.2 to 65.2)60.4 (49.4 to 71.4)53.4 (42.6 to 64.2)
Statistical analysis
  • Computer Training With Active tDCS vs Computer Training With or Without tDCS · Mixed Models Analysis · p = 0.40 · Mean difference (final values): 2.29Estimated marginal means comparisons, Tukey adjustment
SecondaryFunctional Status

Participant performance on observed tasks of daily living. Participants completed the University of California--San Diego Performance Based Skills Assessment, version B. The person assessed is asked to complete several functional tasks, including pretending to make a call on a telephone to change a medical appointment and paying an electric bill by filling out a check. Scores on the first task range form 0 to 9, and from 0 to 11 on the second. These raw scores are then converted to create a final combined score that ranges from 0 to 100, with higher scores indicating a better performance.

Time frame:
3 weeks
Reported as:
Mean · score on a scale
Functional Status
score on a scaleComputer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCS
Functional Status84.6 (74.8 to 94.5)82.8 (72.9 to 92.6)84.4 (74.8 to 94.0)
Statistical analysis
  • Computer Training With Active tDCS vs Computer Training With or Without tDCS · Mixed Models Analysis · p = 0.37 (Estimated marginal means comparisons, Tukey adjustment) · Mean difference (final values): 1.86
SecondaryParticipant Assessment of Own Functioning (PAOF)

Participant self-report of problems related to cognitive and sensory functioning on the Participant Assessment of Own Functioning (PAOF). This is a self-report measure of the frequency with which a person experiences difficulties with various mental and sensory tasks, such as remembering what is said to them, understanding or expressing themselves in language, and thinking about complex problems. The PAOF includes 33 items ranged from 0 to 5, allowing a total score from 0 to 165. A higher score on this measure means that the person is reporting greater frequency with some mental activities.

Time frame:
3 weeks
Reported as:
Mean · score on a scale
Participant Assessment of Own Functioning (PAOF)
score on a scaleComputer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCS
Participant Assessment of Own Functioning (PAOF)7.98 (6.27 to 9.69)7.73 (6.01 to 9.44)7.86 (6.19 to 9.52)
Statistical analysis
  • Computer Training With Active tDCS vs Computer Training With or Without tDCS · Mixed Models Analysis · p = 0.37 · Mean difference (final values): 1.86Comparison of estimated marginal means, Tukey adjustment for multiple comparisons
SecondaryCenter for Epidemiological Studies Depression Scale (CES-D)

Participant self-report of mood. The Center for Epidemiological Studies Depression scale (CES-D) is a self-report measure of symptoms of and related to depressed mood. It includes 20 items that are scored from 0 to 3 and summed for an overall score ranging from 0 to 60. Higher scores on this measure indicate that the person assessed is reporting a greater frequency or severity of depressive symptoms.

Time frame:
3 weeks
Reported as:
Mean · score on a scale
Center for Epidemiological Studies Depression Scale (CES-D)
score on a scaleComputer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCS
Center for Epidemiological Studies Depression Scale (CES-D)16.5 (9.53 to 23.50)16.6 (9.59 to 23.70)16.3 (9.54 to 23.10)
Statistical analysis
  • Computer Training With Active tDCS vs Computer Training With or Without tDCS · Mixed Models Analysis · p = 0.61 · Mean difference (final values): 1.42Differences between estimated marginal means, Tukey correction for multiple comparisons.

Adverse events

Collected over 7 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Computer Training With Active tDCS0/16 (0%)0/16 (0%)1/16 (6.3%)
Computer Training With Sham tDCS0/15 (0%)0/15 (0%)1/15 (6.7%)
Computer Training With or Without tDCS0/15 (0%)0/15 (0%)0/15 (0%)
Most frequent other events
Most frequent other events
EventComputer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCS
DizzinessNervous system disorders0/161/150/15
Reactivation of traumatic memoriesNervous system disorders1/160/150/15

Baseline characteristics

Age, Continuous
Age, Continuous(years)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
Mean57.06 ± 4.9958.80 ± 4.1361.07 ± 6.2958.93 ± 5.35
Sex: Female, Male
Sex: Female, Male(Participants)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
Female3249
Male13131137
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
Hispanic or Latino3306
Not Hispanic or Latino13121540
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American1181029
White57517
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
United States16151546
Psychomotor Speed
Psychomotor Speed(units on a scale)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
Mean48.94 ± 9.2851.67 ± 13.7046.07 ± 15.5248.89 ± 12.93
Functional Status
Functional Status(units on a scale)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
Mean79.75 ± 10.7180.20 ± 19.3976.73 ± 13.7278.91 ± 13.52
Participant Assessment of Own Functioning (PAOF)
Participant Assessment of Own Functioning (PAOF)(units on a scale)Computer Training With Active tDCSComputer Training With Sham tDCSComputer Training With or Without tDCSTotal
Mean8.18 ± 2.347.65 ± 4.468.55 ± 2.498.13 ± 2.40

1 further baseline measures are reported on the registry.

07

Study locations

1 site
  • NSU Psychiatry Research Office
    Fort Lauderdale, Florida 33328, United States
08

References and documents

Publications

  • Ownby RL, Acevedo A. A pilot study of cognitive training with and without transcranial direct current stimulation to improve cognition in older persons with HIV-related cognitive impairment. Neuropsychiatr Dis Treat. 2016 Oct 25;12:2745-2754. doi: 10.2147/NDT.S120282. eCollection 2016. PubMed 27822047 ↗
  • Ownby RL, Kim J. Computer-Delivered Cognitive Training and Transcranial Direct Current Stimulation in Patients With HIV-Associated Neurocognitive Disorder: A Randomized Trial. Front Aging Neurosci. 2021 Nov 15;13:766311. doi: 10.3389/fnagi.2021.766311. eCollection 2021. PubMed 34867291 ↗

Study documents

  • Study protocol · Dec 2, 2020
  • Statistical analysis plan · Dec 2, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — After the conclusion of the study, de-identified study data will be shared by the study principal investigator with interested individuals.

Supporting information: Study protocol

09

Registry details

Key details

Study ID
NCT03440840
Lead sponsor
Nova Southeastern University
Responsible party
Raymond Ownby, M.D. (Professor and Chair, Nova Southeastern University) — Principal investigator
First posted
Feb 22, 2018
Start date
Jan 16, 2018
Primary completion
Nov 6, 2019
Completion
Nov 6, 2019
Results posted
Sep 18, 2023
Last update
Sep 18, 2023

Study contacts

Raymond L Ownby, MD, PhD
principal investigator · Nova Southeastern University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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