MalariaCM_CCRTNCT01743417
Computerized Cognitive Rehabilitation in Children After Severe Malaria
A study testing Computerised cognitive rehabilitation training in people with Malaria, run by Makerere University at 1 site in Uganda.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Computerised cognitive rehabilitation training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUganda
- Study dates
- Apr 2011to 23 Aug 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Aged 5 to 12 years of age;
- Signed consent from the parent/guardian, assent from children aged 7 years and older;
- Completion of their 24 months testing in the parent study (MUREC no 2008-033).
Who cannot join
- CM: elevated cerebrospinal fluid protein, white blood cells or red blood cells
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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:
- To evaluate the effectiveness of CCRT in improving neuropsychological performance and psychiatric outcomes in Ugandan children who survive severe malaria.
- To evaluate whether severity of malaria illness (e.g., immunological brain inflammation, EEG abnormalities) is predictive of neuropsychological benefit from CCRT.
- 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).
- Conditions
- Malaria
- Being tested
- Computerised cognitive rehabilitation training
- Keywords
- Cognitive rehabilitation, malaria, neuropsychology, attention, working memory
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Computerised cognitive rehabilitation trainingBehavioural
Also called Captain's Log
24 sessions of computerised bran training will be provided for 8 weeks (+/-2) with about 3 sessions per week to the intervention arm and active control arms. The program will be programmed to increases in difficulty for the intervention arm. In the active control arms, the difficulty level will not change.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive intervention | Experimental | Children in this arm will receive computerised cognitive rehabilitation training for 24 sessions lasting 45 minutes. The Captain's log brain training software is programmed to increase in difficulty as child progresses through the training levels. Receives: Behavioral: Computerised cognitive rehabilitation training |
| Active control | Active comparator | Children in this arm will receive 24 sessions of computerised cognitive rehabilitation training. Captain's log, the brain training software will not be programmed to increase in difficulty with each successive level in this arm. Receives: Behavioral: Computerised cognitive rehabilitation training |
| Passive control | No intervention | No computer training or games will be provided to this group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Executive attention
Executive attention will be measured by the Test of Variables of Attention
Measured: Measured at 12 months post-intervention
Secondary outcomes (1)
Working memory
Working memory will be measured by the Kaufman Assessment Battery for Children second edition
Measured: Measured at 12 months post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study startApr 2011
- Primary completion23 Aug 2016
- Study completion23 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- Michigan State University, University of Michigan
- Responsible party
- Sponsor
- Investigators
- Michael J Boivin, PhD, Principal investigator, Michigan State UniversityNoeline Nakasujja, PhD, Principal investigator, Makerere University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01743417
- Sponsor's protocol ID
- 1R01HD064416-01A1
- Acronym
- CM_CCRT
- Status last verified
- May 2017
- First submitted
- 5 Sep 2012
- Last updated
- 22 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 21816079Bangirana 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.
PubMed 19668094John 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.
PubMed 18541616Boivin 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.
PubMed 27045714Boivin 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.
PubMed 26580321Boivin 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.
PubMed 31232898
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Computerized Cognitive Rehabilitation in Children After Severe Malaria
- ClinicalTrials.gov ID
- NCT01743417
- Acronym / sponsor ID
- CM_CCRT / 1R01HD064416-01A1
- Conditions
- Malaria
- Keywords
- Cognitive rehabilitation, malaria, neuropsychology, attention, working memory
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Collaborators
- Michigan State University, University of Michigan
- Study start
- Apr 2011 (actual)
- Primary completion
- 23 Aug 2016 (actual)
- Study completion
- 23 Aug 2016 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate the effectiveness of CCRT in improving neuropsychological performance and psychiatric outcomes in Ugandan children who survive severe malaria.
- To evaluate whether severity of malaria illness (e.g., immunological brain inflammation, EEG abnormalities) is predictive of neuropsychological benefit from CCRT.
- 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cognitive intervention | Experimental | Behavioral: Computerised cognitive rehabilitation trainingChildren in this arm will receive computerised cognitive rehabilitation training for 24 sessions lasting 45 minutes. The Captain's log brain training software is programmed to increase in difficulty as child progresses through the training levels. |
| Active control | Active comparator | Behavioral: Computerised cognitive rehabilitation trainingChildren in this arm will receive 24 sessions of computerised cognitive rehabilitation training. Captain's log, the brain training software will not be programmed to increase in difficulty with each successive level in this arm. |
| Passive control | No intervention | –No computer training or games will be provided to this group |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Aged 5 to 12 years of age;
- Signed consent from the parent/guardian, assent from children aged 7 years and older;
- Completion of their 24 months testing in the parent study (MUREC no 2008-033).
Key exclusion criteria (4 listed)
- CM: elevated cerebrospinal fluid protein, white blood cells or red blood cells
- Severe malarial anemia: history of coma, impaired consciousness, repeated seizures, other brain disorder, and developmental delay. Additional exclusion criteria for CC group:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Computerised cognitive rehabilitation trainingAlso: Captain's Log24 sessions of computerised bran training will be provided for 8 weeks (+/-2) with about 3 sessions per week to the intervention arm and active control arms. The program will be programmed to increases in difficulty for the intervention arm. In the active control arms, the difficulty level will not change. | Behavioural | Active control, Cognitive intervention |
Primary outcome
Executive attention
Time frame: Measured at 12 months post-intervention
Executive attention will be measured by the Test of Variables of Attention
1 secondary outcome
Working memory
Time frame: Measured at 12 months post-intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2017.
- Background: PubMed 21816079Bangirana 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.
- Background: PubMed 19668094Bangirana 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.
- Background: PubMed 18541616John 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.
- Background: PubMed 27045714Boivin 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.
- Background: PubMed 26580321Boivin 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.
- Derived from this study: PubMed 31232898Boivin 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.
- Webpage of the Makerere University/Michigan State University research collaborationLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael J Boivin, PhD principal investigator
Michigan State University
Noeline Nakasujja, PhD principal investigator
Makerere University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Computerised cognitive rehabilitation training in people with Malaria, run by Makerere University at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Executive attention (time frame: Measured at 12 months post-intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01743417, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2017.