TY - JOUR
T1 - Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children
T2 - Study protocol for a randomized controlled trial
AU - Cheng, William D.
AU - Wold, Karl J.
AU - Benzoni, Nicole S.
AU - Thakwalakwa, Chrissie
AU - Maleta, Kenneth M.
AU - Manary, Mark J.
AU - Trehan, Indi
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/11/6
Y1 - 2017/11/6
N2 - Background: Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ultimately morbidity and mortality. Effective therapies against EED and stunting are lacking and further clinical trials are warranted to effectively identify and operationalize interventions. Methods/design: A prospective randomized placebo-controlled parallel-group randomized controlled trial will be conducted to determine if a daily supplement of lactoferrin and lysozyme, two important proteins found in breast milk, can decrease the burden of EED and stunting in rural Malawian children aged 12-23 months old. The intervention and control groups will have a sample size of 86 subjects each. All field and laboratory researchers will be blinded to the assigned intervention group, as will the subjects and their caregivers. The percentage of ingested lactulose excreted in the urine (Δ%L) after 4 h will be used as the biomarker for EED and linear growth as the measure of chronic malnutrition (stunting). The primary outcomes of interest will be change in Δ%L from baseline to 8 weeks and to 16 weeks. Intention-to-treat analyses will be used. Discussion: A rigorous clinical trial design will be used to assess the biologically plausible use of lactoferrin and lysozyme as dietary supplements for children at high risk for EED. If proven effective, these safe proteins may serve to markedly reduce the burden of childhood malnutrition and improve survival. Trial Registration: Clinicaltrials.gov, NCT02925026. Registered on 4 October 2016.
AB - Background: Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ultimately morbidity and mortality. Effective therapies against EED and stunting are lacking and further clinical trials are warranted to effectively identify and operationalize interventions. Methods/design: A prospective randomized placebo-controlled parallel-group randomized controlled trial will be conducted to determine if a daily supplement of lactoferrin and lysozyme, two important proteins found in breast milk, can decrease the burden of EED and stunting in rural Malawian children aged 12-23 months old. The intervention and control groups will have a sample size of 86 subjects each. All field and laboratory researchers will be blinded to the assigned intervention group, as will the subjects and their caregivers. The percentage of ingested lactulose excreted in the urine (Δ%L) after 4 h will be used as the biomarker for EED and linear growth as the measure of chronic malnutrition (stunting). The primary outcomes of interest will be change in Δ%L from baseline to 8 weeks and to 16 weeks. Intention-to-treat analyses will be used. Discussion: A rigorous clinical trial design will be used to assess the biologically plausible use of lactoferrin and lysozyme as dietary supplements for children at high risk for EED. If proven effective, these safe proteins may serve to markedly reduce the burden of childhood malnutrition and improve survival. Trial Registration: Clinicaltrials.gov, NCT02925026. Registered on 4 October 2016.
KW - Environmental enteric dysfunction
KW - Environmental enteropathy
KW - Inflammation
KW - Lactoferrin
KW - Lactulose
KW - Lysozyme
KW - Malnutrition
KW - Stunting
UR - http://www.scopus.com/inward/record.url?scp=85032944269&partnerID=8YFLogxK
U2 - 10.1186/s13063-017-2278-8
DO - 10.1186/s13063-017-2278-8
M3 - Article
C2 - 29110675
AN - SCOPUS:85032944269
VL - 18
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 523
ER -