Cassava Intervention Project

Toxicodietary and Genetic Determinants of Susceptibility to Neurodegeneration

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.

Study Overview

• Status: Completed
• Conditions: Neurotoxicity Syndrome, Cassava; Neurotoxicity Syndrome, Cyanate; Neurotoxicity Syndrome, Cyanide; Neurotoxicity Syndrome, Thiocyanate
• Intervention / Treatment: Other: Non Inferiority WTM Interventional Trial

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Kinshasa, Congo, The Democratic Republic of the
    • INRB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Peer-led Intervention; 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; 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.
EXPERIMENTAL: Specialist-led Intervention; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ministry of Public Health, Democratic Republic of the Congo
• Collaborators: National Institutes of Health (NIH); Oregon Health and Science University; National Institute of Environmental Health Sciences (NIEHS); Michigan State University; University of Kinshasa
• Investigators: Study Director: Mumba Ngoyi, Ministry of Health

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 30, 2017
• Primary Completion (ACTUAL): June 1, 2022
• Study Completion (ACTUAL): June 1, 2022

Study Registration Dates

• First Submitted: May 12, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (ACTUAL): May 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Isoprostanes; Oxidative Damage; Cyanide; Cassava; Konzo; Cyanate; Thiocyanate; Carbamoylation
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Disease; Poisoning; Syndrome; Neurotoxicity Syndromes
• Other Study ID Numbers: FWA00017202; R01ES019841 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No