Cassava Intervention Project

Study Overview
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Brief Summary
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Investigators will implement a novel cassava processing method (wetting method, WTM) that safely removes cyanogenic compounds from cassava flour prior to human consumption in a stratified village-cluster randomized non-inferiority trial so as to compare the effectiveness of a peer-led intervention (women training other women in the WTM) with that by community-health worker specialists.

Detailed Description
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The proposed project seeks methods to prevent and elucidate biomarkers of neurocognition and motor deficits associated with chronic dietary reliance on cyanogenic cassava, a staple food crop for more than 600 millions of people living in the tropics. Aim 1 will implement a novel cassava processing method (wetting method, WTM) that safely removes cyanogenic compounds from cassava flour prior to human consumption in a stratified village-cluster randomized non-inferiority trial so as to compare the effectiveness of a peer-led intervention (women training other women in the WTM) with that by community-health worker specialists (2 intervention training arms). Aim 2 will determine whether post-intervention reductions in cassava cyanogenic content and child U-SCN are associated with changes in biomarkers of cassava neurotoxicity particularly 8,12-iso-iPF2α-VI isoprostane (oxidant marker), carbamoylated albumin fragments KVPQVSTPTLVEVSR (residues 438-452) and LDELRDEGKASSAK (residues 206-219), or homocitrulline (carbamoylating markers), and scores at the KABC-II cognition and BOT-2 motor testing.

Official Title
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Toxicodietary and Genetic Determinants of Susceptibility to Neurodegeneration

Conditions
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Neurotoxicity Syndrome, Cassava, Neurotoxicity Syndrome, Cyanate, Neurotoxicity Syndrome, Cyanide, Neurotoxicity Syndrome, Thiocyanate

Intervention / Treatment
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* Other: Non Inferiority WTM Interventional Trial


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Households with a konzo child and non-konzo sibling between 5 and 12 years Presence of a biological mother primarily responsible for the household food preparation and caring for the children Mother consenting to participate in this study Exclusion Criteria: History of seizures History of cerebral malaria History of retroviral (HIV-HTLV) infections

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: We will implement a novel cassava processing method (wetting method, WTM) that safely removes cyanogenic compounds from cassava flour prior to human consumption in a stratified village-cluster randomized non-inferiority trial so as to compare the effectiveness of a peer-led intervention (Arm 1 = women training other women in the WTM) with that by community-health worker specialists (Arm 2= specialist led intervention arm)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peer-led Intervention<br>Peers (community women in leading roles) training other women in the wetting method for safe processing of cassava in a non-inferiority intervention trial. | Other: Non Inferiority WTM Interventional Trial<br>* The intervention will implement the WTM cassava processing technique in participating households. Twenty women (in leading roles) will be our principal candidates to serve as peer trainers. Together with a 20 community health worker specialists, these women will be trained in the WTM technique by the Kinshasa team of community health workers who are experts in the WTM method. Those who master the technique will then be certified as trainers to train and support other small groups of other mothers throughout a two-year period in the implementation of the WTM for the safer processing of food for their families. Both the community health worker specialists and trained women (prospective trainers) would have to be able to bring the cassava cyanogenic content to the lowest achievable level, which must be < 10 ppm as per the recommendations of the World Health Organization.<br>|
| Experimental: Specialist-led Intervention<br>Specialists (nutritionists) training other women in the wetting method for safe processing of cassava in a non-inferiority intervention trial.. | Other: Non Inferiority WTM Interventional Trial<br>* The intervention will implement the WTM cassava processing technique in participating households. Twenty women (in leading roles) will be our principal candidates to serve as peer trainers. Together with a 20 community health worker specialists, these women will be trained in the WTM technique by the Kinshasa team of community health workers who are experts in the WTM method. Those who master the technique will then be certified as trainers to train and support other small groups of other mothers throughout a two-year period in the implementation of the WTM for the safer processing of food for their families. Both the community health worker specialists and trained women (prospective trainers) would have to be able to bring the cassava cyanogenic content to the lowest achievable level, which must be < 10 ppm as per the recommendations of the World Health Organization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in food cyanogenic exposure | Cassava cyanogenic content | From baseline to 6-month time points | 
| Change in internal cyanogenic exposure | Urinary concentrations of thiocyanate (U-SCN) | From baseline to 6-month time points | 
| Change in oxidation damage | Serum isoprostanes | From baseline to 6-month time points | 
| Change in carbamoylation | serum albumin peptidic carbamoylation | From baseline to 6-month time points | 
| Change in carbamoylation surrogate | serum homocitrulline | From baseline to 6-month time points | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognition performance | Kaufman Assessment Battery for Children (KABC-II) for cognition testing score | From baseline to 6-month time points | 
| Change in motor proficiency | Motor proficiency Bruininks/Oseretsky Testing (BOT-2) score | From baseline to 6-month time points | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cassava, Konzo, Cyanide, Cyanate, Thiocyanate, Carbamoylation, Isoprostanes, Oxidative Damage