Malnutrition, Manihot Species Poisoning
Conditions
Brief summary
The proposed research adapted 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
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, this research l 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.
Interventions
BEHAVIORALWetting method (WTM)
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 were distributed to participating households. Women received this training bi-weekly for 12 months.
The study team used 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).
Sponsors
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Michigan State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 4 Years
Healthy volunteers
Yes
Inclusion criteria
* Mother with at least one child aged between 1 and 4 years * Mother is the primary caregiver of child * Mother is 18 years of age or older
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mullen Scales of Early Learning (MSEL) Composite Score | Month 6, month 12 | The Mullen Scales of Early Learning (MSEL) assesses child developmental domains: visual reception, gross motor skills, fine motor skills, receptive language, and expressive language. A composite t-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. The composite t-score ranges from 40 to 130. The t-scores have mean 100 and standard deviation 15 in the Western population. Higher scores reflect better outcome. Measure is applicable to children only, not collected from caregivers |
| Child Urine Thiocyanite Level | Month 6, month 12 | Technicians collected samples of urine on the same day as child assessments, so that they are contiguous with level of cyanide exposure from current poorly processed cassava. Urine thiocyanite levels in urine were measured in micromol per liter. The range was 0-1032, higher scores reflect worse outcome. Data collected from children only, not collected from caregivers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Child Physical Growth: Weight for Age Z-score | Month 6, month 12 | Weight for age z-score was determined using the World Health Organization algorithm using child's length, sex, and age at the time of measurement. The world population mean is 0 with standard deviation 1. |
| Home Observation for the Measurement of the Environment (HOME) Score | Month 6, month 12 | Home Observation for the Measurement of the Environment (HOME) 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 items answered on the scale from 0=none to 3=good. A total HOME score was generated by summing item responses. Potential range is 0 to 135. Higher HOME scores indicate higher quality of home environment. Measure applies to children only. |
| Caregiver Depressive Symptoms | Month 6, month 12 | The modified Hopkins Symptom Checklist was used to assess caregiver depressive symptoms. The instrument included 9 yes/no items, and the item responses were summed into the total score. The potential range was 0-9 with higher score indicating worse depressive symptoms. Measure applies to caregivers only, data were not collected from children. |
| Caregiver Anxiety Symptoms | Month 6, month 12 | The modified Hopkins Symptom Checklist was used to assess caregiver anxiety. The instrument included 9 yes/no items, and the item responses were summed into the total score. The potential range was 0-9 with higher score indicating worse anxiety. Measure applicable to caregiver only. Data were not collected from children. |
| Child Physical Growth: Length for Age Z-score | Month 6, month 12 | Length for age z-score was determined using the World Health Organization algorithm using child's length, sex, and age at the time of measurement. The world population mean is 0 with standard deviation 1. Z-scores of -2 or below are often used to indicate stunting. |
Countries
Democratic Republic of the Congo
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MISC and WTM, Children Wetting method (WTM)+ Mediational Intervention for Sensitizing Caregivers (MISC) bi-weekly for 12 months.
Wetting method (WTM): 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
Mediational Intervention for Sensitizing Caregivers (MISC): 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). | 79 |
| WTM Only, Children WTM trainings only (recommended standard of care) bi-weekly for 12 months.
Wetting method (WTM): 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 | 40 |
| MISC and WTM, Caregivers Wetting method (WTM)+ Mediational Intervention for Sensitizing Caregivers (MISC) bi-weekly for 12 months.
Wetting method (WTM): 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
Mediational Intervention for Sensitizing Caregivers (MISC): 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). | 79 |
| WTM Only, Caregivers WTM trainings only (recommended standard of care) bi-weekly for 12 months.
Wetting method (WTM): 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 | 40 |
| Total | 238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 14 | 4 | 14 | 4 |
Baseline characteristics
| Characteristic | MISC and WTM, Caregivers | WTM Only, Caregivers | Total | MISC and WTM, Children | WTM Only, Children |
|---|---|---|---|---|---|
| Age, Continuous | 28.46 years STANDARD_DEVIATION 8.37 | 27.98 years STANDARD_DEVIATION 9.05 | 15.44 years STANDARD_DEVIATION 4.71 | 2.38 years STANDARD_DEVIATION 0.68 | 2.34 years STANDARD_DEVIATION 0.74 |
| Bradbury Cyanide level cassava flour | 28.89 parts per million STANDARD_DEVIATION 33.1 | 22.03 parts per million STANDARD_DEVIATION 24.39 | 26.87 parts per million STANDARD_DEVIATION 27.23 | 28.89 parts per million STANDARD_DEVIATION 33.1 | 22.03 parts per million STANDARD_DEVIATION 24.39 |
| Caregiver anxiety | 3.29 score on a scale STANDARD_DEVIATION 2.96 | 3.35 score on a scale STANDARD_DEVIATION 2.76 | 3.31 score on a scale STANDARD_DEVIATION 2.88 | — | — |
| Caregiver depression | 3.01 score on a scale STANDARD_DEVIATION 2.37 | 2.38 score on a scale STANDARD_DEVIATION 2.54 | 2.80 score on a scale STANDARD_DEVIATION 2.86 | — | — |
| Child Length for age z-score | — | — | -1.56 Z-score STANDARD_DEVIATION 1.47 | -1.44 Z-score STANDARD_DEVIATION 1.53 | -1.79 Z-score STANDARD_DEVIATION 1.34 |
| Child Mullen Scales Learning Composite | — | — | 73.56 t-score STANDARD_DEVIATION 11.74 | 73.13 t-score STANDARD_DEVIATION 12.09 | 74.41 t-score STANDARD_DEVIATION 11.13 |
| Child urine thiocyanate | — | — | 208.45 Micromol per Liter STANDARD_DEVIATION 202.33 | 179.37 Micromol per Liter STANDARD_DEVIATION 207.35 | 227.57 Micromol per Liter STANDARD_DEVIATION 193.85 |
| Child weight-for-age z-score | — | — | -0.95 Z-score STANDARD_DEVIATION 1.17 | -0.80 Z-score STANDARD_DEVIATION 1.14 | -1.23 Z-score STANDARD_DEVIATION 1.21 |
| HOME score quality caregiving | — | — | 66.36 score on a scale STANDARD_DEVIATION 16.99 | 64.88 score on a scale STANDARD_DEVIATION 18.01 | 69.30 score on a scale STANDARD_DEVIATION 14.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 79 Participants | 40 Participants | 238 Participants | 79 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 79 Participants | 40 Participants | 189 Participants | 47 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 49 Participants | 32 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 40 | 0 / 79 | 0 / 40 |
| other Total, other adverse events | 0 / 79 | 0 / 40 | 0 / 79 | 0 / 40 |
| serious Total, serious adverse events | 0 / 79 | 0 / 40 | 0 / 79 | 0 / 40 |
Outcome results
Primary
Child Urine Thiocyanite Level
Technicians collected samples of urine on the same day as child assessments, so that they are contiguous with level of cyanide exposure from current poorly processed cassava. Urine thiocyanite levels in urine were measured in micromol per liter. The range was 0-1032, higher scores reflect worse outcome. Data collected from children only, not collected from caregivers.
Time frame: Month 6, month 12
Population: Children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Child Urine Thiocyanite Level | Month 6 | 74.98 Micromol per Liter | Standard Error 13.94 |
| MISC and WTM, Children | Child Urine Thiocyanite Level | Month 12 | 146.45 Micromol per Liter | Standard Error 14.36 |
| WTM Only, Children | Child Urine Thiocyanite Level | Month 6 | 139.00 Micromol per Liter | Standard Error 20.17 |
| WTM Only, Children | Child Urine Thiocyanite Level | Month 12 | 108.91 Micromol per Liter | Standard Error 20.18 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Planned sample size of total 100 analyzed was determined by feasibility considerations for this exploratory developmental R21 study. With planned n=66 in MISC+WTM arm and n=34 in WTM only arm, the unadjusted effect size of 0.60 was detectable as statistically significant with power of 0.80 and 0.05 level of significance in two-tailed tests.p-value: 0.0195% CI: [15.26, 112.8]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Planned sample size of total 100 analyzed was determined by feasibility considerations for this exploratory developmental R21 study. With planned n=66 in MISC+WTM arm and n=34 in WTM only arm, the unadjusted effect size of 0.60 was detectable as statistically significant with power of 0.80 and 0.05 level of significance in two-tailed tests.p-value: 0.1395% CI: [-86.92, 11.85]Mixed Models Analysis
Primary
Mullen Scales of Early Learning (MSEL) Composite Score
The Mullen Scales of Early Learning (MSEL) assesses child developmental domains: visual reception, gross motor skills, fine motor skills, receptive language, and expressive language. A composite t-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. The composite t-score ranges from 40 to 130. The t-scores have mean 100 and standard deviation 15 in the Western population. Higher scores reflect better outcome. Measure is applicable to children only, not collected from caregivers
Time frame: Month 6, month 12
Population: Children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Mullen Scales of Early Learning (MSEL) Composite Score | Month 6 | 73.63 t-score | Standard Error 1.33 |
| MISC and WTM, Children | Mullen Scales of Early Learning (MSEL) Composite Score | Month 12 | 77.04 t-score | Standard Error 1.48 |
| WTM Only, Children | Mullen Scales of Early Learning (MSEL) Composite Score | Month 6 | 74.33 t-score | Standard Error 1.9 |
| WTM Only, Children | Mullen Scales of Early Learning (MSEL) Composite Score | Month 12 | 76.75 t-score | Standard Error 1.93 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Planned sample size of total 100 analyzed was determined by feasibility considerations for this exploratory developmental R21 study. With planned n=66 in MISC+WTM arm and n=34 in WTM only arm, the unadjusted effect size of 0.60 was detectable as statistically significant with power of 0.80 and 0.05 level of significance in two-tailed tests.p-value: 0.7795% CI: [-3.93, 5.32]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Planned sample size of total 100 analyzed was determined by feasibility considerations for this exploratory developmental R21 study. With planned n=66 in MISC+WTM arm and n=34 in WTM only arm, the unadjusted effect size of 0.60 was detectable as statistically significant with power of 0.80 and 0.05 level of significance in two-tailed tests.p-value: 0.995% CI: [-5.14, 4.54]Mixed Models Analysis
Secondary
Caregiver Anxiety Symptoms
The modified Hopkins Symptom Checklist was used to assess caregiver anxiety. The instrument included 9 yes/no items, and the item responses were summed into the total score. The potential range was 0-9 with higher score indicating worse anxiety. Measure applicable to caregiver only. Data were not collected from children.
Time frame: Month 6, month 12
Population: Caregivers of children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Caregiver Anxiety Symptoms | Month 6 | 2.86 score on a scale | Standard Error 0.28 |
| MISC and WTM, Children | Caregiver Anxiety Symptoms | Month 12 | 2.80 score on a scale | Standard Error 0.3 |
| WTM Only, Children | Caregiver Anxiety Symptoms | Month 6 | 3.91 score on a scale | Standard Error 0.4 |
| WTM Only, Children | Caregiver Anxiety Symptoms | Month 12 | 3.74 score on a scale | Standard Error 0.41 |
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.0495% CI: [0.07, 2.03]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.0795% CI: [-0.08, 1.96]Mixed Models Analysis
Secondary
Caregiver Depressive Symptoms
The modified Hopkins Symptom Checklist was used to assess caregiver depressive symptoms. The instrument included 9 yes/no items, and the item responses were summed into the total score. The potential range was 0-9 with higher score indicating worse depressive symptoms. Measure applies to caregivers only, data were not collected from children.
Time frame: Month 6, month 12
Population: Caregivers of children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Caregiver Depressive Symptoms | Month 6 | 2.21 score on a scale | Standard Error 0.29 |
| MISC and WTM, Children | Caregiver Depressive Symptoms | Month 12 | 2.45 score on a scale | Standard Error 0.32 |
| WTM Only, Children | Caregiver Depressive Symptoms | Month 6 | 4.25 score on a scale | Standard Error 0.42 |
| WTM Only, Children | Caregiver Depressive Symptoms | Month 12 | 4.18 score on a scale | Standard Error 0.42 |
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: <0.0195% CI: [1.02, 3.06]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: <0.0195% CI: [0.67, 2.79]Mixed Models Analysis
Secondary
Child Physical Growth: Length for Age Z-score
Length for age z-score was determined using the World Health Organization algorithm using child's length, sex, and age at the time of measurement. The world population mean is 0 with standard deviation 1. Z-scores of -2 or below are often used to indicate stunting.
Time frame: Month 6, month 12
Population: Children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Child Physical Growth: Length for Age Z-score | Month 6 | -1.72 z-score | Standard Error 0.09 |
| MISC and WTM, Children | Child Physical Growth: Length for Age Z-score | Month 12 | -1.57 z-score | Standard Error 0.1 |
| WTM Only, Children | Child Physical Growth: Length for Age Z-score | Month 6 | -1.88 z-score | Standard Error 0.13 |
| WTM Only, Children | Child Physical Growth: Length for Age Z-score | Month 12 | -1.96 z-score | Standard Error 0.13 |
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.3295% CI: [-0.48, 0.16]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.0295% CI: [-0.72, -0.06]Mixed Models Analysis
Secondary
Child Physical Growth: Weight for Age Z-score
Weight for age z-score was determined using the World Health Organization algorithm using child's length, sex, and age at the time of measurement. The world population mean is 0 with standard deviation 1.
Time frame: Month 6, month 12
Population: Children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Child Physical Growth: Weight for Age Z-score | Month 12 | -1.40 z-score | Standard Error 0.13 |
| MISC and WTM, Children | Child Physical Growth: Weight for Age Z-score | Month 6 | -1.54 z-score | Standard Error 0.12 |
| WTM Only, Children | Child Physical Growth: Weight for Age Z-score | Month 6 | -1.92 z-score | Standard Error 0.16 |
| WTM Only, Children | Child Physical Growth: Weight for Age Z-score | Month 12 | -2.10 z-score | Standard Error 0.16 |
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.0695% CI: [-0.78, 0.01]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.00195% CI: [-1.11, -0.28]Mixed Models Analysis
Secondary
Home Observation for the Measurement of the Environment (HOME) Score
Home Observation for the Measurement of the Environment (HOME) 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 items answered on the scale from 0=none to 3=good. A total HOME score was generated by summing item responses. Potential range is 0 to 135. Higher HOME scores indicate higher quality of home environment. Measure applies to children only.
Time frame: Month 6, month 12
Population: Children
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MISC and WTM, Children | Home Observation for the Measurement of the Environment (HOME) Score | Month 6 | 69.37 score on a scale | Standard Error 1.7 |
| MISC and WTM, Children | Home Observation for the Measurement of the Environment (HOME) Score | Month 12 | 71.49 score on a scale | Standard Error 1.84 |
| WTM Only, Children | Home Observation for the Measurement of the Environment (HOME) Score | Month 6 | 67.61 score on a scale | Standard Error 2.42 |
| WTM Only, Children | Home Observation for the Measurement of the Environment (HOME) Score | Month 12 | 68.07 score on a scale | Standard Error 2.42 |
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.5595% CI: [-7.65, 4.13]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. Sample size was determined by considerations for the primary outcomes.p-value: 0.2695% CI: [-9.48, 2.63]Mixed Models Analysis