Computerized Cognitive Rehabilitation in Ugandan Children With HIV

NCT ID: NCT00926003

Last Updated: 2019-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2015-11-30

Brief Summary

One-hundred and fifty-nine school-age children with HIV in Kayunga District, Uganda were randomized to one of 3 treatment arms: 24 training sessions of a computerized cognitive rehabilitation therapy (CCRT) program called Captain's Log; 24 sessions of Captain's Log not titrated to child's performance; or no training intervention. Study Aim 1: To compare the neuropsychological benefit of 24 training sessions of Captain's Log CCRT to the active and passive control groups over a 8-week period, and at 3-month follow-up. Study Aim 2: To compare the psychiatric benefit of 24 training sessions of Captain's Log CCRT to the active and passive control groups over an 8-week period, and at 3-month follow-up. Study Aim 3: To evaluate how ART treatment status, and the corresponding clinical stability of the child modifies CCRT neuropsychological performance gains and psychiatric symptom reduction. Outcome Assessments: The Kaufman Assessment Battery for Children, 2nd ed. (KABC-2), Tests of Variables of Attention (TOVA) visual and auditory tests, CogState computerized neuropsychological screening test, Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), and Achenbach Child Behavior Checklist (CBCL) will be administered before and after the 8-week training period and at 3-month follow-up post training. Captain's Log has an internal evaluator feature which will help us monitor the specific training tasks to which the children best respond. Analyses: We will compare neuropsychological and psychiatric gains over the 8-week training period and at 3-mo follow-up for our three study groups, anticipating that they will be significantly greater for the CCRT intervention children (Study Aims 1 & 2). These neuropsychological gains will be associated with improved school performance over the long-term. Intervention children clinically stable on ART will have greater gains than those not stable or virally suppressed on ART. Conclusion: CCRT will prove effective and sustainable for enhancing neurocognitive status in HIV children. Futher work will prove this approach viable for assessing and treating children in resource-poor settings.

Detailed Description

Aim 1. To evaluate the effectiveness of CCRT in improving cognitive performance outcomes in Ugandan children with HIV.

Hypothesis 1a: CCRT can improve short and long-term cognitive outcomes in children with HIV; Hypothesis 1b: Improvements in performance associated with CCRT are not solely due to increased computer exposure.

One-hundred and fifty school-age children with HIV in Kayunga District, Uganda, will undergo baseline neuropsychological testing using the Kaufman Assessment Battery for Children (KABC-2), the computerized Tests of Variables of Attention (TOVA: auditory and visual tests), the brief CogState computerized neuropsychological test battery (CogState), and the Bruininks-Oseretsky Tests of Motor Proficiency (2nd edition) (BOT-2). Cogstate is designed as a neuropsychological screening tool with minimal practice effects and suitable in a repeated measures design for monitoring the benefits of treatment on neurocognitive disability11. Children then will be randomized to either: CCRT intervention group (Captain's Log active rehabilitation), active control group (Captain's Log locked, non-rehabilitation mode), or passive control group (no computer intervention). CCRT or computer controls will be presented over 24 sessions (~ 45 min) for 8 weeks (3 sessions per week). After the 8-weeks, neurocognitive gains will be assessed with CogState and the KABC-2 working memory subscales (primary expected outcome measures). The full KABC-2, TOVA, CogState, and BOT-2 will be re-administered 3 months after the 8-week assessment. Thus, the full battery will be administered at enrollment and at 3-month follow-up, while the most strategic portions of the battery will be administered following the 8 weeks CCRT intervention period. The combined testing will allow us to assess both the short-term and longer-term neuropsychological benefits of CCRT.

Aim 2. To evaluate the effectiveness of CCRT in reducing psychiatric symptoms in Ugandan children with HIV.

Hypothesis 2: CCRT can reduce short- and long-term psychiatric symptoms in children with HIV.

Previously in cerebral malaria survivors, we demonstrated a significant reduction in short-term symptoms related to anxiety, depression, and somatic complaints as assessed by the Achenbach Child Behavior Checklist (CBCL) following CCRT intervention12. In this aim, caregiver-reported psychiatric symptoms on the CBCL will be assessed at enrollment, after the 8-week CCRT intervention period, and 3 months after enrollment. The CBCL assessment will also help us gauge the psychosocial benefits of the social attention and enrichment surrounding computer exposure in the active control condition, rather than the rehabilitative aspects of CCRT per se. This will be evident as we compare the active and passive control groups.

Aim 3. To evaluate how ARV treatment status and clinical response along with corresponding immunological status of the child modifies CCRT neuropsychological performance gains and psychiatric symptom reduction; .after controlling for quality of home environment, nutrition, and other risk factors of poverty.

Hypothesis 3: Children virally suppressed on ART treatment with a history of fewer opportunistic illnesses and better CD4 counts will have better neuropsychological outcomes in response to CCRT training.The moderating effects of HIV progressive encephalopathy on brain plasticity can also be monitored by CCRT training progress, measures by the Captain's Log Internal Evaluator (CLIE) feature of the CCRT program.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Full Computerized Cognitive Training

Intervention is a Computer Cognitive Rehabilitation Training delivered in 24 sessions over 8 weeks (3 times/week). A training session lasts about an hour and consists of 9 training games or programs, 3 pertaining to improving attention, 3 pertaining to improving visual-spatial memory, and 3 pertaining to improving reasoning/planning. Each training game become more difficult as the child gains proficiency.

Group Type: EXPERIMENTAL

Full Computerized cognitive training

Intervention Type: BEHAVIORAL

8 weeks of 3 times weekly intervention for 60 min per session with the full titrating version of Captain's Log program (3 games for attention, 3 games for visual spatial working memory, 3 games for reasoning/planning

Control

Passive Control with no intervention training (computer cognitive games) for 8 weeks.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Limited computerized cognitive training

Intervention is a Computer Cognitive Rehabilitation Training delivered in 24 sessions over 8 weeks (3 times/week). A training session lasts about an hour and consists of 9 training games or programs, 3 pertaining to improving attention, 3 pertaining to improving visual-spatial memory, and 3 pertaining to improving reasoning/planning. In this arm, however, the training games do NOT become progressively more difficult as the child gains proficiency, but rotates randomly among simpler to moderate levels of difficulty for each game. The purpose to to give children int he "limited" CCRT arm comparable exposure to the cognitive games training as with the "full CCRT" arm, with the exception of the titrating nature of the game training.

Group Type: ACTIVE_COMPARATOR

Limited computerized cognitive training

Intervention Type: BEHAVIORAL

Locked Captain's Log CCRT that rotates randomly among simplest level of computer cognitive games training. 8 weeks of 3 times weekly intervention for 60 min per session with the non-titrating version of Captain's Log program (3 games for attention, 3 games for visual spatial working memory, 3 games for reasoning/planning).

Interventions

Full Computerized cognitive training

8 weeks of 3 times weekly intervention for 60 min per session with the full titrating version of Captain's Log program (3 games for attention, 3 games for visual spatial working memory, 3 games for reasoning/planning

Intervention Type: BEHAVIORAL

Limited computerized cognitive training

Locked Captain's Log CCRT that rotates randomly among simplest level of computer cognitive games training. 8 weeks of 3 times weekly intervention for 60 min per session with the non-titrating version of Captain's Log program (3 games for attention, 3 games for visual spatial working memory, 3 games for reasoning/planning).

Intervention Type: BEHAVIORAL

Other Intervention Names

computerized cognitive games; computerized cognitive rehabilitation therapy (CCRT); computerized cognitive rehabilitation therapy (CCRT)

Eligibility Criteria

Inclusion Criteria

• HIV children 6 to 16 years of age and enrolled in the CAI program will be eligible should the parent or caregiver consent to participation in the study. They will all be confirmed HIV positive children (ELISA and Western blot). Only children with perinatally acquired HIV infection will be included.

Exclusion Criteria

• At pre-CCRT medical examination (see medical exam form in appendices) we will exclude children with a medical history of serious birth complications, severe malnutrition, bacterial meningitis, encephalitis, cerebral malaria, or other known brain injury or disorder requiring hospitalization. Also children with seizure or other neurological disability will be excluded. This will be screened using a brief medical history questionnaire and CAI medical chart review.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Global Health Uganda LTD

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

Michigan State University

OTHER

Sponsor Role: lead

Responsible Party

Michael J. Boivin

Professor of Psychiatry and Neurology & Ophthalmology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael J. Boivin, PhD, MPH

Role: STUDY_DIRECTOR

MSU Psychiatry

Locations

Global Health Uganda

Kampala, , Uganda

Countries

Uganda

References

Ruisenor-Escudero H, Familiar I, Nakasujja N, Bangirana P, Opoka R, Giordani B, Boivin M. Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda. Glob Ment Health (Camb). 2015 Jun 25;2:e9. doi: 10.1017/gmh.2015.7. eCollection 2015.

Reference Type: RESULT

PMID: 28596857 (View on PubMed)

Giordani B, Novak B, Sikorskii A, Bangirana P, Nakasujja N, Winn BM, Boivin MJ. Designing and evaluating Brain Powered Games for cognitive training and rehabilitation in at-risk African children. Glob Ment Health (Camb). 2015 May 29;2:e6. doi: 10.1017/gmh.2015.5. eCollection 2015.

Reference Type: RESULT

PMID: 28596854 (View on PubMed)

Boivin MJ, Nakasujja N, Sikorskii A, Opoka RO, Giordani B. A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV. AIDS Res Hum Retroviruses. 2016 Aug;32(8):743-55. doi: 10.1089/AID.2016.0026. Epub 2016 May 2.

Reference Type: RESULT

PMID: 27045714 (View on PubMed)

Other Identifiers

R34MH085631

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

BIRB 07-709

Identifier Type: -

Identifier Source: org_study_id