Caregiver Training to Prevent Konzo Disease in Children in Democratic Republic of Congo

Study Overview
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Brief Summary
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The proposed research will adapt the caregiver training and child neurodevelopmental assessment capacity that the PI previously built in Uganda beginning in 2008, to a community-based intervention model for the prevention of konzo in the Democratic Republic of Congo.

Detailed Description
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Early childhood (1 through 4 yrs) is a period of dramatic developmental change that can be seriously compromised by exposure to toxic cyanogenic cassava (konzo disease), with potentially great impact throughout central and western sub-Sahara Africa in regions dependent on this food staple. In the face of ongoing economic instability and nutritional, medical and educational deprivation affecting konzo at-risk communities in the Democratic Republic of Congo, no programs exist for sustaining a favorable developmental milieu for these children. By establishing the viability of caregiver training interventions to enhance functionality among caregivers and improve caregiving quality while preventing konzo, the present R21 proposal can benefit tens of millions of children at-risk neurodevelopmentally; not only from poorly processed cyanogenic cassava, but also from a myriad of other non-infectious and infectious diseases.

Official Title
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Caregiver Early Child Development Training for Preventing Konzo From Toxic Cassava in the Democratic Republic of Congo

Conditions
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Malnutrition, Manihot Species Poisoning

Intervention / Treatment
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* Behavioral: Wetting method (WTM)
* Behavioral: Mediational Intervention for Sensitizing Caregivers (MISC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kahemba district households with at least 1 child 4 years or younger Mother is the primary caregiver of child Exclusion Criteria: History of brain injury (infectious, traumatic, birth) in child Konzo disease in any family member of household Epilepsy in child Any neurodisability in child Caregiver is unable to participate in the year-long training Caregiver or child are presently enrolled in our parent R01 study

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MISC and WTM<br>Wetting method (WTM)+ Mediational Intervention for Sensitizing Caregivers (MISC) bi-weekly for 12 months. | Behavioral: Wetting method (WTM)<br>* The wetting method is an evidence-based, simple process to remove cyanogens from cassava flour. It involves teaching women to add water to cassava flour and allow it to stand for 2 h in the sun or 5 h in the shade for the hydrogen cyanide gas to escape. Colorfully illustrated and durable laminated posters depicting the WTM will be distributed to participating households. Women will receive this training bi-weekly for 12 months<br>Behavioral: Mediational Intervention for Sensitizing Caregivers (MISC)<br>* The study team will use MISC to train DRC mothers in practical day-to-day activities with their children to enhance 5 key mediational processes: 1) focusing (getting the child's attention and engaging directing them to learning experiences); 2) exciting (communicating excitement, appreciation, and affection with the learning experience); 3) expanding (making the child aware of how the learning experience transcends the present situation and can include past and future issues beyond the immediate need of the moment); 4) encouraging (emotional support to foster the child's sense of security and competence); and 5) regulating (helping to direct the child's behavior in constructive ways with a goal towards self-regulation).<br>|
| Active Comparator: WTM only<br>WTM trainings only (recommended standard of care) bi-weekly for 12 months. | Behavioral: Wetting method (WTM)<br>* The wetting method is an evidence-based, simple process to remove cyanogens from cassava flour. It involves teaching women to add water to cassava flour and allow it to stand for 2 h in the sun or 5 h in the shade for the hydrogen cyanide gas to escape. Colorfully illustrated and durable laminated posters depicting the WTM will be distributed to participating households. Women will receive this training bi-weekly for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mullen Scales of Early Learning (MSEL) scores | The MSEL is a comprehensive test assessing specific developmental domains: visual reception, gross motor skills, fine motor skills, receptive language, and expressive language. Each sub-scale produces a raw and a standardized score. A composite score derived from standardized t-scores of the four domains (excluding gross motor) provides a measure of g, the general measure of fluid intelligence thought to underlie general cognitive ability. | Baseline, 6-months, and 12 months post-enrollment | 
| Change in the Observed Mediational Interventions (OMI) scores for home-based videos | Home-based video recordings of mother-child interactions while feeding, bathing and playing will be scored by a trained observer using an ad hoc rubric covering areas of focusing, exciting, expanding, encouraging, and regulating caregiver/child interactions consistent with the MISC training | Baseline, 6-months, and 12 months post-enrollment | 
| Change in urine thiocyanite level | Technicians will collect samples of urine and cassava flour on the same day as child assessments, so that they are contiguous with level of cyanide exposure from current poorly processed cassava. We will measure thiocyanite levels (micromol/l) in urine using the SCN picrate kit D1 and B2 protocols. We will measure the cyanide-yielding capacity in household cassava flour, and thiocyanate (SCN, metabolite of cyanide) in urine | Baseline, 6-months, and 12 months post-enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Home Observation for the Measurement of the Environment (HOME) score | Composite measure designed to assess the quality and quantity of stimulation that the child is exposed to in their home environment. The Infant/Toddler version includes 45 yes/no items. A total HOME score was generated by summing the number of 'yes' responses; higher HOME scores indicate higher quality interactions. | Baseline, 6-months, and 12 months post-enrollment | 
| Change in Hopkins Symptoms Checklist-25 (HSCL) scores | Questionnaire consisting of two subscales: anxiety (10 items) and depression (15 items) symptoms to evaluate caregiver well-being. Caregivers indicate how frequently they experienced each symptom in the last two weeks on a scale of 0 (not at all) to 3 (a lot). Subscale scores will be calculated by averaging item responses. | Baseline, 6-months, and 12 months post-enrollment | 
| Change in Caregiver functional impairment for caregiving daily activities score | 12-item measure assessing degree of difficulty performing tasks women regularly do to care for themselves, their family, their community and their young child. Caregivers indicate how much difficulty they had completing each task, with responses ranging from 0 (no difficulty at all) to 4 (cannot complete). An impairment scale will be calculated by averaging item responses | Baseline, 6-months, and 12 months post-enrollment | 
| Change in upper-motor neuron neurological symptoms of konzo disease | Neurological evaluation to establish study eligibility with no symptoms of konzo disease. This neurological exam will also be used as a primary outcome for WTM adherence and low levels of cyanide exposure by quantifying the number and severity of each symptom using a rubric | Baseline, 6-months, and 12 months post-enrollment | 
| Change in physical growth measures | World Health Organization standardized weight and height will be combined to report BMI in kg/m^2 | Baseline, 6-months, and 12 months post-enrollment | 
| Change in neurodisability score | The Durkin Ten Question Questionnaire (TQQ) screening inventory to assess number and severity of neurodisabilities. It is a parent report screening tool for developmental disabilities, that has been used in epidemiological studies, surveys and as a clinical screening tool. An average score is derived summing all responses | Baseline, 6-months, and 12 months post-enrollment |