Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: study protocol for a randomized controlled trial

Abstract

BackgroundChronic 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/designA 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.DiscussionA 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 RegistrationClinicaltrials.gov, NCT02925026. Registered on 4 October 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2278-8) contains supplementary material, which is available to authorized users.

Expression of OLFM4 and Lysozyme During Necrotizing Enterocolitis and Volvulus in Newborns: a Comparative Observational Research Study

“…However, the exact mechanisms of OLFM4 and LYZ function and their role in immunological responses have not yet been resolved. These observations of a comparative observational research study add new insights as basis for further large-scale population research and potential new therapeutic targets such as daily supplementation of LYZ [31,33]. This study was approved by the local ethical committees (ethics of the medical faculty of the Ruprecht-Karls-Universität of Heidelberg, Germany; ethics committee of the medical faculty of the Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany) and was performed in line with the principles of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.…”

Increased expression of OLFM4 and lysozyme during necrotizing enterocolitis in neonates: an observational research study

“…However, the exact mechanisms of OLFM4 and LYZ function and their role in immunological responses have not yet been resolved. These observations of an observational research study add new insights as basis for further large-scale population research and potential new therapeutic targets such as daily supplementation of LYZ [ 31 , 36 ].…”

Enteric infection and dysfunction—A new target for PLOS Neglected Tropical Diseases

“…A small pilot study in young Kenyan children with severe acute malnutrition and stunting concluded that mesalamine was safe to administer in the population and observed modest reductions in markers of intestinal inflammation (fecal calprotectin) and systemic inflammation (plasma Immunoglobulin G to endotoxin core antibody) in the treatment arm but reported better nutritional recovery in the placebo arm [38]. An upcoming publication will report on the results of a clinical trial in Malawi that tested the effect of lactoferrin and lysozyme administration on intestinal integrity and growth in infants [39]. Results from two major cluster-randomized studies of WASH interventions, the WASH Benefits trial (Bangladesh and Kenya) and SHINE (Zimbabwe), examined whether such interventions impact growth, gut integrity, or inflammation.…”