Lactoferrin and Lysozyme Supplementation for Long-term Diarrhea Sequelae

NCT05519254 | Recruiting Phase 3 DMC

• 2 other identifiers: STUDY000117591R01HD103642-01
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 4

Brief Summary

Children in low- and middle-income countries who are hospitalized for diarrhea and also have malnutrition are at high risk for illness and death in the 6 months period following treatment for diarrhoea despite receiving current guideline recommended diarrhea management (such as oral rehydration solution, or "ORS"). This study will test whether nutritional supplements made from milk (lactoferrin or lysozyme) or a combination of the two (lactoferrin and lysozyme) will prevent children from having repeated diarrhea episodes and help improve their nutrition by improving their stomach health or preventing new disease during this 6-month period. The study is taking place at 7 hospitals in Western Kenya. Six hundred participants will be enrolled if they provide informed consent to participate, are aged 6-24 months, were hospitalized with diarrhea and malnutrition and have been managed by the facility nutritionists and ready to return home. Participation in the study will entail providing information on the child's health history, collection of stool samples, blood, and potentially urine. The caregiver will be provided sachets of the investigational product to take home and mix daily with their child's porridge or other complimentary food, and asked to return to the clinic 4 times in the subsequent 6 months, and also consent to having a community health worker visit their home every two weeks for a follow up visit. The risks to the participant and their caregiver are minimal. The information gained in this study will help us create new treatments and develop new strategies to treat sick children to prevent death and illness.

Conditions

Diarrhea; Wasting; Malnutrition, Child

Outcome Measures

Primary Outcomes (2)

• Incidence of moderate-to-severe diarrhea

  Defined as total number of new diarrhea episodes (\> 48 hours after a diarrhea-free period) deemed moderate-to-severe, divided by the child-time at risk during the 6-month follow-up period. Moderate-to-severe diarrhea will be defined as ≥ 3 using the CODA (Community DiarrhoeA) diarrhea severity score or dysentery (evidence or reported visible blood in stool).

  6 months

• Time to nutritional recovery

  Defined as the number of days since enrollment to the date of the second of two consecutive MUAC measurements ≥ 12.5 cm.

  6 months

Secondary Outcomes (23)

• Incidence of diarrhea (any severity)

  6 months

• Incidence of severe diarrhea

  6 months

• Incidence of dysentery

  6 months

• Incidence of medically-attended diarrhea

  6 months

• Cumulative duration of diarrhea

  6 months

Study Arms (4)

Lactoferrin Arm

EXPERIMENTAL

16-week course of lactoferrin

Dietary Supplement: Lactoferrin

Lysozyme Arm

EXPERIMENTAL

16-week course of lysozyme

Dietary Supplement: Lysozyme

Combination Arm (Lactoferrin + Lysozyme)

EXPERIMENTAL

16-week course of lactoferrin and lysozyme

Combination Product: Lactoferrin + Lysozyme

Placebo Arm

PLACEBO COMPARATOR

16-week course of taste/appearance-matched placebo

Other: Placebo

Interventions

Lactoferrin DIETARY_SUPPLEMENT

Caregivers of children will be instructed to provide 1.5g of lactoferrin with 40g of unmodified rice powder daily mixed with 125 mL of porridge or other complimentary food.

Lactoferrin Arm

Lysozyme DIETARY_SUPPLEMENT

Caregivers of children will be instructed to provide 41.5g of Lysosure daily mixed with 125 mL of porridge or other complimentary food.

Lysozyme Arm

Lactoferrin + Lysozyme COMBINATION_PRODUCT

Caregivers of children will be instructed to provide 40g of Lysosure with 1.5 grams of lactoferrin daily mixed with 125 mL of porridge or other complimentary food.

Combination Arm (Lactoferrin + Lysozyme)

Placebo OTHER

Caregivers of children will be instructed to provide 41.5 grams of unmodified rice powder daily mixed with 125 mL of porridge or other complimentary food.

Placebo Arm

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age 6-24 months
• Managed as an outpatient or inpatient for diarrhea at one of the recruiting sites
• MUAC \<12.5 cm at the time of screening
• Plan to stay within the study area for the next 6 months or greater

You may not qualify if:

• Age younger than 6 months or older than 24 months
• Caregiver does not provide consent to study participation
• History of 2 or more blood transfusions in the past 12 months
• Exclusively breastfeeding at the time of enrollment
• History of congenital defect or syndrome that prevents age-appropriate feeding (e.g. cleft palate)
• History of allergy to dairy products
• Child is not ready to return home (is not yet discharged), or discharged against medical advice
• Unwilling to participate in the dual sugar permeability sub-study if selected
• Enrollment in another study

Sponsors & Collaborators

• University of Washington: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (4)

Homa Bay County Referral Hospital

Homa Bay, Kenya

RECRUITING

Isebania Sub-County Hospital

Isibania, Kenya

RECRUITING

Kisii Teaching and Referral Hospital

Kisii, Kenya

RECRUITING

Rongo Sub-County Hospital

Rongo, Kenya

RECRUITING

Related Publications (9)

• Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013 Aug 3;382(9890):427-451. doi: 10.1016/S0140-6736(13)60937-X. Epub 2013 Jun 6.

  PMID: 23746772 BACKGROUND

• Tickell KD, Pavlinac PB, John-Stewart GC, Denno DM, Richardson BA, Naulikha JM, Kirera RK, Swierczewski BE, Singa BO, Walson JL. Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea. Am J Trop Med Hyg. 2017 Nov;97(5):1337-1344. doi: 10.4269/ajtmh.17-0139.

  PMID: 29140236 BACKGROUND

• Talbert A, Ngari M, Bauni E, Mwangome M, Mturi N, Otiende M, Maitland K, Walson J, Berkley JA. Mortality after inpatient treatment for diarrhea in children: a cohort study. BMC Med. 2019 Jan 28;17(1):20. doi: 10.1186/s12916-019-1258-0.

  PMID: 30686268 BACKGROUND

• Tickell KD, Sharmin R, Deichsel EL, Lamberti LM, Walson JL, Faruque ASG, Pavlinac PB, Kotloff KL, Chisti MJ. The effect of acute malnutrition on enteric pathogens, moderate-to-severe diarrhoea, and associated mortality in the Global Enteric Multicenter Study cohort: a post-hoc analysis. Lancet Glob Health. 2020 Feb;8(2):e215-e224. doi: 10.1016/S2214-109X(19)30498-X.

  PMID: 31981554 BACKGROUND

• Brander RL, Pavlinac PB, Walson JL, John-Stewart GC, Weaver MR, Faruque ASG, Zaidi AKM, Sur D, Sow SO, Hossain MJ, Alonso PL, Breiman RF, Nasrin D, Nataro JP, Levine MM, Kotloff KL. Determinants of linear growth faltering among children with moderate-to-severe diarrhea in the Global Enteric Multicenter Study. BMC Med. 2019 Nov 25;17(1):214. doi: 10.1186/s12916-019-1441-3.

  PMID: 31767012 BACKGROUND

• Cheng WD, Wold KJ, Bollinger LB, Ordiz MI, Shulman RJ, Maleta KM, Manary MJ, Trehan I. Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial. Am J Gastroenterol. 2019 Apr;114(4):671-678. doi: 10.14309/ajg.0000000000000170.

  PMID: 30829679 BACKGROUND

• Ochoa TJ, Chea-Woo E, Baiocchi N, Pecho I, Campos M, Prada A, Valdiviezo G, Lluque A, Lai D, Cleary TG. Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children. J Pediatr. 2013 Feb;162(2):349-56. doi: 10.1016/j.jpeds.2012.07.043. Epub 2012 Aug 30.

  PMID: 22939927 BACKGROUND

• Zavaleta N, Figueroa D, Rivera J, Sanchez J, Alfaro S, Lonnerdal B. Efficacy of rice-based oral rehydration solution containing recombinant human lactoferrin and lysozyme in Peruvian children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2007 Feb;44(2):258-64. doi: 10.1097/MPG.0b013e31802c41b7.

  PMID: 17255841 BACKGROUND

• Tiwari R, Tickell KD, Yoshioka E, Otieno J, Shah A, Richardson BA, Keter L, Okello M, Nyabinda C, Trehan I, McGrath CJ, Means AR, Houpt ER, Liu J, Platts-Mills JA, Njunge JM, Rwigi D, Diakhate MM, Nyaoke J, Ochola E, John-Stewart G, Walson JL, Pavlinac PB, Singa BO. Lactoferrin and lysozyme to promote nutritional, clinical and enteric recovery: a protocol for a factorial, blinded, placebo-controlled randomised trial among children with diarrhoea and malnutrition (the Boresha Afya trial). BMJ Open. 2024 Aug 9;14(8):e079448. doi: 10.1136/bmjopen-2023-079448.

  PMID: 39122384 DERIVED

MeSH Terms

Conditions

Diarrhea; Cachexia; Child Nutrition Disorders

Interventions

Lactoferrin; Muramidase

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Weight Loss; Body Weight Changes; Body Weight; Thinness; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Glycoproteins; Glycoconjugates; Carbohydrates; Transferrins; Iron-Binding Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Lactoglobulins; Whey Proteins; Milk Proteins; Animal Proteins, Dietary; Dietary Proteins; Globulins; Metalloproteins; Glycoside Hydrolases

Study Officials

• Patricia B Pavlinac

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruchi Tiwari

CONTACT

2067904389; ruchit@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, SPH: Global Health

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 29, 2022
• Study Start: March 10, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: After publication.
• Access Criteria: Publicly available

Locations

KE (4)