BPG Intervention, Control
Conditions
Keywords
cognitive games, attention, memory, learning, reasoning, planning, HIV, African, children
Brief summary
The investigators will use Brain Power Games as a neurocognitive stress test or medical challenge test, in order to evaluate or improve brain/behavior functional integrity in HIV-affected children. This dual use of BPG is a key innovative feature. Each of the 5 core BPG games lasts 10 minutes and trains fine motor, monitoring/attention, visual/auditory working memory, spatial navigational learning. The investigator's central hypothesis is that the BPG performance gains will be improved compared to waitlist control for children in Uganda and Malawi.
Detailed description
We randomize equal numbers of each of three exposure groups of children (perinatally HIV infected, perinatally HIV-exposed but not infected, and unexposed/uninfected children) to one of two intervention arms. They are randomized to either the Brain Powered Games (BPG) intervention arm of 12 sessions of hour-long training (twice a day for several days weekly at the study clinic), or to the wait-listed arm of no BPG training sessions. Separate analyses by country (Uganda and Malawi) are planned. HIV exposure status is used for balancing of randomization.
Interventions
BEHAVIORALCognitive Games Training
Brain Powered Games (BPG) uses games for neurocognitive assessment and training, using images and sounds more familiar to African children. As a computerized cognitive rehabilitation training (CCRT) program designed for Sub-Saharan African school-age children, it can help children infected affected directly or indirectly by HIV. BPG consists of 5 core games evaluating different cognitive abilities (learning, memory, language, attention). Each game includes a visual tutorial, several adjustable settings on the administrative side (Admin), and records game play data for research purposes. Village Builder (VB) is a pro-social reasoning/planning world building strategy type game intended to evaluate frontal lobe executive functions in a culture-friendly and enjoyable game manner. It consists of many of the village artistic components as used in BPG but orchestrated into a village setting where children must gather resources and protect them in order to expand the capacity of the village.
Sponsors
University of Michigan
Johns Hopkins University
MU-JHU CARE
Kamuzu University of Health Sciences
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Michigan State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
The subject population for this proposal will consist of 600 children roughly equally divided between males and females and between HIV exposed uninfected and HIV unexposed and uninfected. These are Ugandan and Malawian children 5-12 years of age at study initiation who live in Uganda or Malawi.
Eligibility
Sex/Gender
ALL
Age
5 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* HEU and HUU children at least 5 yrs of age and older from the PROMISE ND study (Uganda and Malawi) * HIV+ children from P1104s (Uganda and Malawi) * HUU children age-matched from PROMISE ND and P1104s study cohorts (Uganda and Malawi)
Exclusion criteria
* Medical history of serious birth complications * Severe malnutrition * Bacterial meningitis * Encephalitis * Cerebral malaria * Other known brain injury or disorder requiring hospitalization * Seizures or other neurological disabilities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 2, month 6 | The KABC mental processing index (MPI) is a summary score across domains. The normative mean 100 and standard deviation 15 are based on American norms. Range is 43 to 160. Higher score reflects better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 2, month 6 | TOVA is a computerized visual continuous performance test used in to screen, diagnose and monitor children and adults at risk for ADHD. TOVA consists of the rapid (tachistoscopic) presentation of a large geometric square on the computer screen with a smaller dark box either in the upper position (signal) or lower position (non-signal). The child is asked to press a switch in response to the signal (measuring vigilance attention), but to withhold responding to the non-signal (measuring impulsivity). The potential range of the TOVA ADHD index is from -10 to 10, higher score is better. |
| Cognitive State (CogState) Correct Moves Per Second | Month 2, month 6 | CogState presents a 30-minute session that includes playing cards in a game-like manner to assess memory, attention, discrimination learning, and executive function that is non-language dependent. The number of correct moves per second during maze learning reflects executive functioning/planning. The range is from 0 to 5. Higher number reflects better outcome. |
Countries
Malawi, Uganda
Participant flow
Pre-assignment details
Randomization was stratified by HIV exposure status (infected, exposed uninfected, unexposed uninfected) to ensure the same distribution of HIV exposure by trial arm (BPG or waitlist control). The study hypotheses were based on comparisons of BPG versus waitlist control arm across all children separately in Uganda and Malawi.
Participants by arm
| Arm | Count |
|---|---|
| BPG, Uganda Children in Uganda randomized to BPG
Cognitive Games Training: Brain Powered Games (BPG) uses games for neurocognitive assessment and training, using images and sounds more familiar to African children. As a computerized cognitive rehabilitation training (CCRT) program designed for Sub-Saharan African school-age children, it can help children infected affected directly or indirectly by HIV. BPG consists of 5 core games evaluating different cognitive abilities (learning, memory, language, attention). Each game includes a visual tutorial, several adjustable settings on the administrative side (Admin), and records game play data for research purposes. Village Builder (VB) is a pro-social reasoning/planning world building strategy type game intended to evaluate frontal lobe executive functions in a culture-friendly and enjoyable game manner. It consists of many of the village artistic components as used in BPG but orchestrated into a village setting where children must gather resources and protect them in order to expand the capacity of the village. | 149 |
| Waitlist Control, Uganda Children in Uganda randomized to waitlist control | 150 |
| BPG, Malawi Children in Malawi randomized to BPG
Cognitive Games Training: Brain Powered Games (BPG) uses games for neurocognitive assessment and training, using images and sounds more familiar to African children. As a computerized cognitive rehabilitation training (CCRT) program designed for Sub-Saharan African school-age children, it can help children infected affected directly or indirectly by HIV. BPG consists of 5 core games evaluating different cognitive abilities (learning, memory, language, attention). Each game includes a visual tutorial, several adjustable settings on the administrative side (Admin), and records game play data for research purposes. Village Builder (VB) is a pro-social reasoning/planning world building strategy type game intended to evaluate frontal lobe executive functions in a culture-friendly and enjoyable game manner. It consists of many of the village artistic components as used in BPG but orchestrated into a village setting where children must gather resources and protect them in order to expand the capacity of the village. | 149 |
| Waitlist Control, Malawi Children in Malawi randomized to waitlist control | 151 |
| Total | 599 |
Baseline characteristics
| Characteristic | Waitlist Control, Uganda | BPG, Malawi | BPG, Uganda | Waitlist Control, Malawi | Total |
|---|---|---|---|---|---|
| Age, Continuous | 9.01 years STANDARD_DEVIATION 2.33 | 8.87 years STANDARD_DEVIATION 2.12 | 8.71 years STANDARD_DEVIATION 2.41 | 9.03 years STANDARD_DEVIATION 2.3 | 8.95 years STANDARD_DEVIATION 2.21 |
| Cognitive State (CogState) correct moves per second | 0.15 number of moves per second STANDARD_DEVIATION 0.09 | 0.14 number of moves per second STANDARD_DEVIATION 0.17 | 0.13 number of moves per second STANDARD_DEVIATION 0.1 | 0.16 number of moves per second STANDARD_DEVIATION 0.2 | 0.15 number of moves per second STANDARD_DEVIATION 0.18 |
| HIV status HIV exposed uninfected | 59 Participants | 59 Participants | 60 Participants | 61 Participants | 239 Participants |
| HIV status HIV infected | 30 Participants | 29 Participants | 30 Participants | 31 Participants | 120 Participants |
| HIV status HIV unexposed uninfected | 61 Participants | 61 Participants | 59 Participants | 59 Participants | 240 Participants |
| Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | 71.65 units on a scale STANDARD_DEVIATION 11.05 | 70.47 units on a scale STANDARD_DEVIATION 10.03 | 71.54 units on a scale STANDARD_DEVIATION 9.83 | 68.82 units on a scale STANDARD_DEVIATION 11.59 | 69.64 units on a scale STANDARD_DEVIATION 10.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 150 Participants | 149 Participants | 149 Participants | 151 Participants | 599 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Malawi | 0 participants | 149 participants | 0 participants | 151 participants | 300 participants |
| Region of Enrollment Uganda | 150 participants | 0 participants | 149 participants | 0 participants | 299 participants |
| Sex: Female, Male Female | 76 Participants | 82 Participants | 71 Participants | 75 Participants | 304 Participants |
| Sex: Female, Male Male | 74 Participants | 67 Participants | 78 Participants | 76 Participants | 295 Participants |
| Test of Variables of Attention (TOVA) attention deficit hyperactivity disorder (ADHD) index | -1.50 units on a scale STANDARD_DEVIATION 2.96 | -3.14 units on a scale STANDARD_DEVIATION 3.3 | -1.72 units on a scale STANDARD_DEVIATION 3.12 | -3.16 units on a scale STANDARD_DEVIATION 3.1 | -3.15 units on a scale STANDARD_DEVIATION 3.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 149 | 0 / 150 | 0 / 149 | 0 / 151 |
| other Total, other adverse events | 0 / 149 | 0 / 150 | 0 / 149 | 0 / 151 |
| serious Total, serious adverse events | 0 / 149 | 0 / 150 | 0 / 149 | 0 / 151 |
Outcome results
Primary
Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI)
The KABC mental processing index (MPI) is a summary score across domains. The normative mean 100 and standard deviation 15 are based on American norms. Range is 43 to 160. Higher score reflects better outcome.
Time frame: Month 2, month 6
Population: Children in Uganda and Malawi
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BPG, Uganda | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 2 | 77.18 units on a scale | Standard Error 0.6 |
| BPG, Uganda | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 6 | 77.27 units on a scale | Standard Error 0.6 |
| Waitlist Control, Uganda | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 6 | 76.46 units on a scale | Standard Error 0.61 |
| Waitlist Control, Uganda | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 2 | 74.79 units on a scale | Standard Error 0.61 |
| BPG, Malawi | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 2 | 71.79 units on a scale | Standard Error 0.71 |
| BPG, Malawi | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 6 | 73.40 units on a scale | Standard Error 0.69 |
| Waitlist Control, Malawi | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 2 | 73.72 units on a scale | Standard Error 0.72 |
| Waitlist Control, Malawi | Kaufman Assessment Battery for Children 2nd Edition (KABC-II) Mental Processing Index (MPI) | Month 6 | 73.61 units on a scale | Standard Error 0.7 |
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: <0.0195% CI: [0.78, 4.01]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.3295% CI: [-0.8, 2.44]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.0795% CI: [-3.74, 0.16]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.8395% CI: [-2.1, 1.68]Mixed Models Analysis
Secondary
Cognitive State (CogState) Correct Moves Per Second
CogState presents a 30-minute session that includes playing cards in a game-like manner to assess memory, attention, discrimination learning, and executive function that is non-language dependent. The number of correct moves per second during maze learning reflects executive functioning/planning. The range is from 0 to 5. Higher number reflects better outcome.
Time frame: Month 2, month 6
Population: Children in Uganda and Malawi.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BPG, Uganda | Cognitive State (CogState) Correct Moves Per Second | Month 2 | 0.23 moves per second | Standard Error 0.01 |
| BPG, Uganda | Cognitive State (CogState) Correct Moves Per Second | Month 6 | 0.27 moves per second | Standard Error 0.01 |
| Waitlist Control, Uganda | Cognitive State (CogState) Correct Moves Per Second | Month 6 | 0.25 moves per second | Standard Error 0.01 |
| Waitlist Control, Uganda | Cognitive State (CogState) Correct Moves Per Second | Month 2 | 0.21 moves per second | Standard Error 0.01 |
| BPG, Malawi | Cognitive State (CogState) Correct Moves Per Second | Month 2 | 0.20 moves per second | Standard Error 0.01 |
| BPG, Malawi | Cognitive State (CogState) Correct Moves Per Second | Month 6 | 0.23 moves per second | Standard Error 0.01 |
| Waitlist Control, Malawi | Cognitive State (CogState) Correct Moves Per Second | Month 2 | 0.18 moves per second | Standard Error 0.01 |
| Waitlist Control, Malawi | Cognitive State (CogState) Correct Moves Per Second | Month 6 | 0.22 moves per second | Standard Error 0.01 |
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.0195% CI: [0.004, 0.043]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.0295% CI: [0.003, 0.04]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.1995% CI: [-0.01, 0.05]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.1995% CI: [-0.01, 0.04]Mixed Models Analysis
Secondary
Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index
TOVA is a computerized visual continuous performance test used in to screen, diagnose and monitor children and adults at risk for ADHD. TOVA consists of the rapid (tachistoscopic) presentation of a large geometric square on the computer screen with a smaller dark box either in the upper position (signal) or lower position (non-signal). The child is asked to press a switch in response to the signal (measuring vigilance attention), but to withhold responding to the non-signal (measuring impulsivity). The potential range of the TOVA ADHD index is from -10 to 10, higher score is better.
Time frame: Month 2, month 6
Population: Children in Uganda and Malawi.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BPG, Uganda | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 2 | -1.21 units on a scale | Standard Error 0.21 |
| BPG, Uganda | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 6 | -0.81 units on a scale | Standard Error 0.21 |
| Waitlist Control, Uganda | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 6 | -0.83 units on a scale | Standard Error 0.21 |
| Waitlist Control, Uganda | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 2 | -1.08 units on a scale | Standard Error 0.21 |
| BPG, Malawi | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 2 | -2.63 units on a scale | Standard Error 0.25 |
| BPG, Malawi | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 6 | -2.23 units on a scale | Standard Error 0.24 |
| Waitlist Control, Malawi | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 2 | -2.35 units on a scale | Standard Error 0.25 |
| Waitlist Control, Malawi | Test of Variables of Attention (TOVA) Attention Deficit Hyperactivity Disorder (ADHD) Index | Month 6 | -2.15 units on a scale | Standard Error 0.24 |
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.6595% CI: [-0.71, 0.42]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.9595% CI: [-0.54, 0.58]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.3495% CI: [-0.92, 0.13]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two arms were equal. The alternative hypothesis was that means of two arms were not equal. With this sample size, differences between arms corresponding to the unadjusted effect size Cohen's d=0.33 would be detectable as statistically significant with power of .80 in two-sided tests at .05 level of significance.p-value: 0.8195% CI: [-0.73, 0.58]Mixed Models Analysis