Clinical trial NCT01743417: Computerized Cognitive Rehabilitation in Children After Severe Malaria
Official title: Computerized Cognitive Rehabilitation in Children After Severe Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Keywords: Cognitive rehabilitation
malaria
neuropsychology
attention
working memory
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: Michigan State University
name: University of Michigan
First posted: 2012-12-06
Enrollment: 300
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Brain training exercises will be provided to children who survived an episode of severe malaria. These children will be given assessments for cognition, behaviour and executive functions before and after the brain training exercises.

Detailed description: Background:

Our Fogarty "Brain Disorders" R21 study findings demonstrated that attention and working memory deficits persist in one out of four children with cerebral malaria (CM) (Boivin et al., 2007; John, Bangirana et al., 2008). Uganda has one of the highest incidences of malaria worldwide (\~480/1000) with about 10% of these incidents becoming severe and over 90% of such cases occurring in children (Snow, Guerra, Noor, Myint, \& Hay, 2005). This results in an estimated 80 thousand new cases each year of Ugandan children with mild to severe neurocognitive impairment from this disease. Such impairment will likely compromise their school performance, impede their activities of daily living, and lessen their future economic opportunities.

There is no known treatment intervention during acute illness to prevent CM brain-injury effects (Abubakar et al., 2007). Nor are neurocognitive rehabilitative treatment programs available in low-resource settings for affected children. However, we have successfully piloted a computerized cognitive rehabilitation therapy (CCRT) intervention to specifically improve attention, visual-spatial learning, and psychosocial adjustment (domains shown most affected by CM in our previous studies) with school-age Ugandan CM survivors (Bangirana, Giordani et al., 2009). This evidence justifies an R01 for further study.

The present application proposes a randomized control trial (RCT) to further establish that CCRT can improve attention, working memory, aspects of executive functioning, and psychosocial adjustment in pediatric CM survivors. Such programs are already being used extensively with children with developmental disabilities (e.g., Attention Deficit Hyperactivity Disorder, learning disorders) and brain injury in high-income countries. The evidence from RCT studies for these interventions is strong enough to warrant the evaluation of CCRT for at-risk African children (Bangirana, Idro, John, \& Boivin, 2006; Boivin \& Giordani, 2009). CCRT could also then be extended to a variety of other infectious diseases causing brain injury and persisting neurocognitive deficits to children in this setting (e.g., HIV, schistosomiasis, meningitis, encephalitis, and neurocysticercosis).

Objectives:

1. To evaluate the effectiveness of CCRT in improving neuropsychological performance and psychiatric outcomes in Ugandan children who survive severe malaria.
2. To evaluate whether severity of malaria illness (e.g., immunological brain inflammation, EEG abnormalities) is predictive of neuropsychological benefit from CCRT.
3. METHODS

Study design:

Randomized controlled trial

Study Population:

Our proposed study groups of children aged 5 to 12 years will consist of 150 children with severe malaria (either cerebral malaria or severe malaria anemia). From the homes of these severe malaria children, we will also recruit 1 sibling (or neighbor child) 5 to 12 years of age without a history of cerebral malaria or other known infectious disease that could cause brain injury (Community Controls from Home: CC children N = 150).

Eligibility criteria: Inclusion Criteria:

1. Aged 5 to 12 years of age;
2. Signed consent from the parent/guardian, assent from children aged 7 years and older;
3. Completion of their 24 months testing in the parent study (MUREC no 2008-033).

Exclusion Criteria:

1. CM: elevated cerebrospinal fluid protein, white blood cells or red blood cells
2. Severe malarial anemia: history of coma, impaired consciousness, repeated seizures, other brain disorder, and developmental delay. Additional exclusion criteria for CC group:

   * any active illness; recent illness or recovery from illness;
   * chronic illness requiring medical care; -) medical abnormalities on screening history or physical exam.

Primary outcomes:
measure: Executive attention
timeFrame: Measured at 12 months post-intervention
Secondary outcomes:
measure: Working memory
timeFrame: Measured at 12 months post-intervention
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Makerere University
Study officials:
affiliation: Michigan State University
name: Michael J Boivin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Makerere University
name: Noeline Nakasujja, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bangirana P, Allebeck P, Boivin MJ, John CC, Page C, Ehnvall A, Musisi S. Cognition, behaviour and academic skills after cognitive rehabilitation in Ugandan children surviving severe malaria: a randomised trial. BMC Neurol. 2011 Aug 4;11:96. doi: 10.1186/1471-2377-11-96.
citation: Bangirana P, Giordani B, John CC, Page C, Opoka RO, Boivin MJ. Immediate neuropsychological and behavioral benefits of computerized cognitive rehabilitation in Ugandan pediatric cerebral malaria survivors. J Dev Behav Pediatr. 2009 Aug;30(4):310-8. doi: 10.1097/DBP.0b013e3181b0f01b.
citation: John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics. 2008 Jul;122(1):e92-9. doi: 10.1542/peds.2007-3709. Epub 2008 Jun 9.
citation: 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.
citation: Boivin MJ, Kakooza AM, Warf BC, Davidson LL, Grigorenko EL. Reducing neurodevelopmental disorders and disability through research and interventions. Nature. 2015 Nov 19;527(7578):S155-60. doi: 10.1038/nature16029.
citation: Boivin MJ, Sikorskii A, Nakasujja N, Ruisenor-Escudero H, Familiar-Lopez I, Opoka RO, Giordani B. Evaluating Immunopathogenic Biomarkers During Severe Malaria Illness as Modifiers of the Neuropsychologic Benefits of Computer Cognitive Games Rehabilitation in Ugandan Children. Pediatr Infect Dis J. 2019 Aug;38(8):840-848. doi: 10.1097/INF.0000000000002367.