Cognitive Rehabilitation in Ugandan Children With HIV (HIV CCRT)
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|ClinicalTrials.gov Identifier: NCT00926003|
Recruitment Status : Suspended (awaiting additional funding)
First Posted : June 23, 2009
Last Update Posted : June 23, 2009
|First Submitted Date ICMJE||June 22, 2009|
|First Posted Date ICMJE||June 23, 2009|
|Last Update Posted Date||June 23, 2009|
|Study Start Date ICMJE||October 2009|
|Estimated Primary Completion Date||October 2011 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Neuropsychologcial Performance (CogState, KABC2, TOVA) [ Time Frame: 8 weeks intervention, pre- post-, and 3 mo follow-up assessments ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
||Psychiatric symptom reduction (CBCL) [ Time Frame: pre-intervention, post intervention, 3 mo follow-up ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Cognitive Rehabilitation in Ugandan Children With HIV|
|Official Title ICMJE||Neuropsychological Benefits of Cognitive Training in Ugandan HIV Children|
|Brief Summary||Research Topic: Over 110,000 HIV Ugandan children are at risk for neurocognitive disorders due to the progressive encephalopathy of CNS HIV infection. Even if clinically stable, these children can have motor, attention, memory, visual-spatial processing, and other executive function impairment. One-hundred and fifty school-age children with HIV in Kayunga District, Uganda, will serve as our participants. Fifty of these children will be randomly selected to receive 24 training sessions of a computerized cognitive rehabilitation therapy (CCRT) program called Captain's Log, marketed mostly for American children with attention or learning problems. A locked version of Captain's Log which does not direct the child's training in a progressive manner will be administered to a second "active control" group; while a third group will be a passive control group not receiving any computer 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 HIV subtype, 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. We have previously used all these assessments with Ugandan children with HIV to effectively evaluate neuropsychological and psychiatric problems. Captain's Log has an internal evaluator feature which will help us monitor the specific training tasks to which the children best respond. Based on our prior research with Kayunga children with HIV, we anticipate that about 40% of our sample will be on ART at study enrollment, and about 20% will be Subtype D while 60% will be subtype A. We also observed that children with HIV Subtype A are at greater risk for neurocognitive deficits. 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 on ART will have greater gains than those not on ART, and HIV subtype D children will have lower viral loads and higher lymphocyte activation levels, resulting in greater gains from CCRT (Study Aim 3). Conclusion: CCRT will prove effective and sustainable in potentiating the neurocognitive benefit of ART in HIV children. It will prove viable for assessing and treating children in resource-poor settings.|
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 HIV subtype and the 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: More aggressive HIV infection type accompanied by higher viral load and lower T-cell lymphocyte levels will decrease neural plasticity, as evidenced by lessened cognitive or psychiatric improvement after CCRT.
Our preliminary data indicates that specific HIV Subtype A in Ugandan children results in higher viral loads and lower T-lymphocyte levels in school-age children, as compared to Subtype D infection. These were associated with poorer neuropsychological outcomes. Likewise, in our preliminary HIV CCRT study Ugandan children with HIV, lower CD8 and CD4 activation levels in children receiving CCRT intervention resulted in less neuropsychological benefits from training. We will evaluate the moderating effects of HIV subtype, ART treatment, and corresponding immunological profile, on CCRT neuropsychological and psychiatric benefit. 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 program.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
|Condition ICMJE||HIV Infections|
|Publications *||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.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Suspended|
|Actual Enrollment ICMJE
|Original Actual Enrollment ICMJE||Same as current|
|Estimated Study Completion Date||October 2012|
|Estimated Primary Completion Date||October 2011 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||6 Years to 16 Years (Child)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Uganda|
|Removed Location Countries|
|NCT Number ICMJE||NCT00926003|
|Other Study ID Numbers ICMJE||BIRB 07-709
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Michael J. Boivin, Associate Professor of Neurology and of Psychiatry, Michigan State University|
|Study Sponsor ICMJE||Michigan State University|
|Investigators ICMJE||Not Provided|
|PRS Account||Michigan State University|
|Verification Date||June 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP