ELICIT 2.0: Pilot Study of the Effect of Maternal Protein Supplementation During Lactation on Childhood Growth

Haydom Global Health Research Center in north central Tanzania represents an important rural setting for performing high-quality medical research in sub-Saharan Africa. The region around Haydom is agricultural (predominantly maize-based), is resource-poor and has a high degree of stunting among local infants-with 70% stunting by 18 months in the MAL-ED study and 50% in the ELICIT study (for Early Life Interventions for Childhood Growth and Development In Tanzania). While the causes of this stunting are multifactorial, a potential contributor is early-life nutritional deficiencies, including inadequate dietary protein.

One likely source of low protein delivery to infants is from low intake among area mothers during lactation, with potential effects on breast milk protein content and child weight gain. The current study is a pilot study assessing our study team's ability to successfully deliver protein-containing food products (a balanced-energy protein supplement) to lactating mother is in the area and assessing whether consumption of these food products improves childhood growth in the 1st year of life. This is a pilot study because of the potential difficulties in distributing these products on a large scale for daily consumption. As such, we aim to demonstrate an effective distribution network, a means of assessing adherence, and measuring endpoints while gathering knowledge regarding community acceptance. The current pilot project will evaluate the effectiveness of distribution and adherence on approximately 100 mother/child dyads. If effective, a future project could involve a large enough sample to be powered to detect reasonable changes in linear growth. .

So, while the current proposal is not adequately powered to prove a hypothesis, the hypothesis underlying the study design is that daily protein supplementation delivered as a balanced protein product (Plumpy'mum) to lactating mothers for 3 months during the period from 0-6 months post-natal life will result in an increase in infant length-for-age Z-score (LAZ) by end of treatment. LAZ will be compared to controls from prior studies in the area.

Study Overview

• Status: Active, not recruiting
• Conditions: Malnutrition; Growth Failure; Stunting; Protein Malnutrition
• Intervention / Treatment: Dietary supplement: Plumpy'Mum

Detailed Description

In severely under-resourced areas of the world, such as the Haydom area in Tanzania (TZ), poor nutrition continues contributes to worsened health-related outcomes including growth and cognitive development. Haydom Global Health Research Center at Haydom Lutheran Hospital in north central Tanzania represents an important rural setting for performing high-quality medical research in sub-Saharan Africa. Through ongoing work in the area around Haydom in the MAL-ED and ELICIT studies, we have been attempting to improve outcomes for children in an area of severe poverty, where there is considerable malnutrition and potential sequelae:

1. Growth deficits: Poor weight gain and linear growth failure in childhood are often seen as surrogates for overall health status; persistently poor growth has implications for future work potential and lower human capital. There was a high degree of stunting in the Haydom site of Tanzanian in the multi-country observational MAL-ED study, which found that the Haydom site had the highest prevalence of stunting among all the MAL-ED sites. This degree of stunting is likely multi-factorial, though one contributor is food availability, as rates of key factors such as birthweight vary significantly according to food availability. An interim analysis of data from our ongoing ELICIT study (for Early Life Interventions for Childhood

Developmental delays: Perhaps there is no more important outcome (with the exception of mortality) than the cognitive, social and emotional development of a population, with clear extensions to human capital, economic productivity and quality of life in communities. Indeed, many observational and interventional studies (including the current study) follow growth as an outcome because of its overall association with cognitive development. In MAL-ED assessments, TZ children had fewer words than seen among US children. The reasons for potential developmental delays are multifactorial, but again malnutrition may play an important role. Studies in other developing areas have demonstrated improved cognitive development following delivery of nutrition support.

Nutritional Causes of Poor Growth

While the causes of the stunting and developmental delays are multifactorial, a potential contributor is early-life nutritional deficiencies, including inadequate dietary protein. One likely source of low protein delivery to infants is from low intake among area mothers during lactation, with potential effects on breast milk protein content and child weight gain. Indeed, the first six months of life represents a critical phase of nutrition for the developing infant, in which all (or nearly all) nutrition is delivered through the mother's breast milk. However, it is not known whether protein supplementation during lactation in this setting would improve childhood growth and reduce stunting-or whether any improvements in growth would continue beyond the period of maternal supplementation.

Assessing the potential effect of mothers receiving protein supplementation-using a balanced energy protein supplement-on childhood growth and development would require an approach that incorporates an effective distribution network, a means of assessing adherence, and a thorough knowledge of community acceptance, as well as accurate measures of endpoints on a large enough sample to be powered to detect reasonable changes in linear growth. In order to assess the feasibility of this type of approach on a smaller scale (which could be later be expanded), the current pilot project will evaluate the effectiveness of distribution and adherence on approximately 100 mother/child dyads. If this experimental approach is feasible and shows promise, it is our hope to follow it with a larger study that offers more definitive evidence of efficacy.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tanzania
  • Manyara
    • Mbulu, Manyara, Tanzania
      • Haydom Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Maternal age >/= 18 years
• Current pregnancy or infant </= 3 months

Exclusion Criteria:

• Maternal inability to adhere to protocol
• Multiple gestation
• Significant birth defect
• Maternal allergy to peanut, milk or soy
• Lack of breast feeding at enrollment (and lack of intention to continue breast feeding at time of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Plumpy'Mum; Mother/child dyads will be enrolled at child age 0-3 months and mothers will immediately begin consuming a packet of Plumpy'Mum (or similar protein food product) daily. Plumpy'Mum will be provided by the study team to the mother, who will consume this however she desires (i.e., alone or with other food). Intervention will continue for 3 months. The rational is that Plumpy'Mum consumption will improve the quality of the breast milk the child is consuming, contributing to improved growth over time. Growth will be compared to historical controls from prior studies in the area.

Dietary supplement: Plumpy'Mum; Mothers will consume Plumpy'Mum (one packet daily) from enrollment (child age 0-3 months) for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Family perception of Plumpy'Mum	Families will be queried about their impression of Plumpy'Mum	at 3 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Child weight-for-age Z-score (WAZ) after 3 months of Plumpy'Mum use	Child weight for WHO Z-score after 3 months of Plumpy'Mum use compared to historical controls	3 months
Child head circumference-for-age Z-score (HCZ) after 3 months of Plumpy'Mum use	Child head circumference for WHO Z-score after 3 months of Plumpy'Mum use compared to historical controls	3 months
Child mid-upper arm circumference-for-age Z-score (MUAC-Z) after 3 months of Plumpy'Mum use	Child mid-upper arm circumference Z-score after 3 months of Plumpy'Mum use compared to historical controls	3 months
Child length-for-age Z-score (LAZ) after 3 months of Plumpy'Mum use	Child length for WHO Z-score after 3 months of Plumpy'Mum use compared to historical controls	3 months
Adverse events	Number of adverse events in intervention arm, compared to historical controls	3 months
Maternal weight at 3 months	Maternal weight at 3 months compared to historical controls	3 months
Maternal mid-upper arm circumference-for-age Z-score (MUAC) at 3 months	Maternal mid-upper arm circumference at 3 months compared to historical controls	12 months

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Bill and Melinda Gates Foundation; Haydom Lutheran Hospital
• Investigators: Principal Investigator: Mark D DeBoer, MD, MSc, MCR, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: growth; Tanzania; infant; breast feeding; protein; eggs; Ready-to-eat food
• Additional Relevant MeSH Terms: Nutrition Disorders; Severe Acute Malnutrition; Malnutrition; Failure to Thrive; Kwashiorkor
• Other Study ID Numbers: 21967

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We will assess platforms for sharing individual participant data following final data analysis.
• IPD Sharing Time Frame: Within 1 year after publication of results
• IPD Sharing Access Criteria: Contact PI to request
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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