Clinical trial NCT05477901: Impacts of Cash Transfers on Child Neurodevelopment (Auxilio Brasil)
Official title: Mental Health and Bolsa Familia: A Mechanistically Focused Clinical Trial of a Cash Transfer Intervention on Child Brain, Behavior, and Mental Health
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Inflammation
HPA
CBCL
Family Relations
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-07-28
Enrollment: 450
Sex: ALL
Minimum age (years): 23
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Post-baseline Procedure -- Random Assignment to Intervention After baseline, families will be randomized in a 1:1 ratio to receive either a high ($40/month) or low ($2/month) supplemental transfer for 2 years and remains in their study arm throughout the study after randomization
Primary purpose: BASIC_SCIENCE

Brief summary: This study examines the impact of Auxilio Brasil (AB), a cash transfer program to mothers of school-age children, on resource-deprived populations in Brazil and its protective effects on child neurodevelopment and mental health. The investigators will conduct a randomized clinical trial (RCT) among those already receiving AB in which 300 families will be randomized in a 1:1 ratio to receive either a high ($40/month) or low ($2/month) supplemental transfer for 2 years. Three hundred children (index child participants; 7-10 years old) will be enrolled across both study arms. Additionally, up to 150 siblings ("sibling participants;" 7-10 years old) will be enrolled. Eligible families who decide to participate will sign a study-specific informed consent (mother) and assent (child) form. The UNIFESP team will conduct the respective assessments at baseline, approximately 8- and 16- months, 24-months and approximately 6-months post-RCT.

Aim 1: Determine the impact of high vs low cash transfers on children's exposure to adversities (ACEs) and neurodevelopment.

Aim 2: Determine the impact of cash transfers on children's inflammatory markers and HPA activity/cortisol.

Exploratory Aim: The investigators will explore (i) whether sex/gender of the children moderates the pathways in the above mediation model; and (ii) whether cash transfer-related effects persist 6 months post-RCT.

Detailed description: Numerous studies link childhood poverty with altered neurodevelopment with the most robust effects often in brain substrates related to executive functions (EF). Poverty is associated with reduced grey matter thickness and surface area of the prefrontal cortex (PFC), a key structure underlying EF (4,5) Poverty is also associated with altered structure and function of the hippocampus - a region essential for memory and cognitive control (5,6). Effects of poverty on brain development are thought to give rise to the well described associations between poverty, impairments in EF, and risk for mental illness (18). The possibility of lifting children out of poverty and thereby tempering poverty's malignant neurodevelopmental effects remains largely untested, particularly with brain and behavioral measures and within LMICs where poverty is widespread. To address this gap, the investigators propose a randomized clinical trial (RCT) to be conducted in low-income families in Sao Paulo, Brazil that will examine causal effects of a cash transfer program on neurodevelopment in youth. Our study builds off an existing cash transfer program (CTP) - Auxilio Brasil (AB) - and augments the cash transfer amount to a level sufficient to lift a family out of extreme poverty and poverty. Our RCT design will allow for novel causal inferences linking cash transfers to brain/behavior outcomes, while testing mechanistic hypotheses. Because the investigators are building off AB, a well-established program with a successful, national infrastructure for transferring cash, our findings could rapidly move toward implementation. Our study will inform critical unanswered questions about pasting, and CTPs generally, that could support their broader and more targeted implementation - First, if augmenting AB removes a family from poverty, does this protect child neurodevelopment? And second, if this augmented AB program protects neurodevelopment, what are the mechanisms that explain this? Providing this mechanistic framework is a key step toward refining AB and other CTPs, facilitating for example, studies aimed at targeting populations most likely to benefit, optimizing the dose/amount of the transfers, and determining the ideal timing/duration of CTPs.

Aims and Hypotheses

Aim 1: Determine the impact of high vs low cash transfers on children's exposure to adversities (ACEs) and neurodevelopment. Eligible families will be those already enrolled in Brazil's national AB program. Relative to low cash transfers, children of mothers who received high cash transfers will have:

Hypothesis 1A (H1A) - \[ACEs\] fewer new onset ACEs over the 24-month course of the RCT; H1B - \[Neurodevelopment\] greater pre-vs-post RCT increases in prefrontal activation during an EF fMRI task (Simon task),10 increased connectivity within EF-related PFC/mesolimbic circuits (resting fMRI and diffusion MRI), and improvements in EF behaviors.

Aim 2: Determine the impact of cash transfers on children's inflammatory markers and HPA activity/cortisol.

Hypothesis 2A (H2A) - Relative to low cash transfers, children of mothers who received high cash transfers will have lower pre vs-post RCT levels of pro-inflammatory markers (e.g., CRP, Il-6, TNF-a; from blood draws) and hair cortisol (HPA activity over past 2-3 months).

Hypothesis 2B (H2B) - Inflammatory and HPA activity levels (H2A) will be lower in children with fewer new onset ACEs (i.e., new ACEs occurring during the 24-month RCT). H2C \[Mediation\] - The effects of high cash transfers on neurodevelopment (H1B) will be mediated by the impact of cash transfers on reducing new onset ACEs (H1A) and lower inflammation and HPA activity (H2A \& H2B), while taking into account covariates and three additional pathways (see A.9 And C.6.3).

Exploratory Aim: The investigators will explore (i) whether sex/gender of the children moderates the pathways in the above mediation model (H2C); and (ii) whether cash transfer-related effects - reducing new onset ACEs and symptoms (CBCL), and improved EF behavior - persist 6 months post-RCT.

Impact: Designed to decrease inequalities, AB is one of the largest social interventions in the world, yet its impact on child mental health is unknown. Our strategy, rather than relying on prohibitively expensive multi-site designs, proposes to generate evidence about the impact of AB on child neurodevelopmental outcomes by focusing on specific, well-supported mechanisms that may underlie mental illness risk. Our findings will have strong implications for tailoring the impact of cash transfer policies to maximize child mental health gains.

Eligibility criteria: Mother:

Inclusion Criteria:

1. Age 23-45 years old
2. Receiving AB cash transfers
3. Has at least two or more children ages 7- 10 years old at time of recruitment (up to 4 children per family)
4. Able to consent

Exclusion Criteria:

1. Mother and child do not reside in same household

Child:

Inclusion Criterion

1. Age 7-10 years old
2. Intellectual Disability

Exclusion Criterion

1. Does not reside in same household as the mother
2. Major Axis I disorder (e.g., Autism, Schizophrenia, Bipolar)
3. Severe Disability
4. MRI contradictions (index child only)

Primary outcomes:
measure: Adverse Childhood Experiences (ACEs) - FHE
timeFrame: Baseline
measure: Changes in Adverse Childhood Experiences (ACEs) - FHE
timeFrame: 8 months
measure: Changes in Adverse Childhood Experiences (ACEs) - FHE
timeFrame: 16 months
measure: Changes in Adverse Childhood Experiences (ACEs) - FHE
timeFrame: 24 months
measure: Changes in Adverse Childhood Experiences (ACEs) - FHE
timeFrame: 6 months post-RCT
measure: Adverse Childhood Experiences (ACEs) - CTC
timeFrame: Baseline
measure: Changes in Adverse Childhood Experiences (ACEs) - CTC
timeFrame: 8 months
measure: Changes in Adverse Childhood Experiences (ACEs) - CTC
timeFrame: 16 months
measure: Changes in Adverse Childhood Experiences (ACEs) - CTC
timeFrame: 24 months
measure: Changes in Adverse Childhood Experiences (ACEs) - CTC
timeFrame: 6 months-post RCT
measure: Child internalizing and externalizing symptoms
timeFrame: Baseline
measure: Changes in Child internalizing and externalizing symptoms
timeFrame: 8 months
measure: Changes in Child internalizing and externalizing symptoms
timeFrame: 16 months
measure: Changes in Child internalizing and externalizing symptoms
timeFrame: 24 months
measure: Changes in Child internalizing and externalizing symptoms
timeFrame: 6 months-post RCT
measure: Access to health care
timeFrame: Baseline
measure: Changes in Access to health care
timeFrame: 8 months
measure: Changes in Access to health care
timeFrame: 16 months
measure: Changes in Access to health care
timeFrame: 24 months
measure: Child brain MRI scan
timeFrame: Baseline
measure: Changes in Child brain MRI scan
timeFrame: 24 months
measure: Child Executive Function
timeFrame: Baseline
measure: Changes in Child Executive Function
timeFrame: 24 months
measure: Changes in Child Executive Function
timeFrame: 6 months-post RCT
measure: Biospecimen - Child hair sample
timeFrame: Baseline
measure: Biospecimen - Changes in Child hair sample
timeFrame: 24 months
measure: Biospecimen - Blood Draw - IL-6
timeFrame: Baseline
measure: Biospecimen - Blood Draw - Change in IL-6
timeFrame: 24 months
measure: Biospecimen - Blood Draw - CRP
timeFrame: Baseline
measure: Biospecimen - Blood Draw - Change in CRP
timeFrame: 24 months
measure: Family Adaptability and Cohesion Evaluation Scale-III (FACES-III)
timeFrame: Baseline
measure: Change in Family Adaptability and Cohesion Evaluation Scale-III (FACES-III)
timeFrame: 24 months
Secondary outcomes:
measure: Food insecurity
timeFrame: Baseline, 24 months
measure: Changes in Food insecurity
timeFrame: 24 months
measure: Home observation/environment
timeFrame: Baseline
measure: Changes in Home observation/environment
timeFrame: 24 months
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: São Paulo
country: Brazil
facility: UNIFESP
state: SP
Study officials:
affiliation: New York State Psychiatric Institute
name: Cristiane Duarte, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of São Paulo
name: Andrea Jackowsi, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Jonathan Posner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York State Psychiatric Institute
name: Tenneill Murray, MPH
role: STUDY_DIRECTOR
References: