DiarrheaPhase 3NCT05519254
Lactoferrin and Lysozyme Supplementation for Long-term Diarrhea Sequelae
A Phase 3 study testing Lactoferrin, Lysozyme and Lactoferrin + Lysozyme in people with Diarrhea and Wasting, run by University of Washington at 4 sites in Kenya.
Trial 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"). Read more about this study
- Who is it for?
- Ages 6 to 24 monthsHealthy volunteers can take part
- Conditions the study is for
- Diarrhea, Wasting, Malnutrition, Child
- What is being tested?
- Lactoferrin, Lysozyme and Lactoferrin + Lysozyme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 4 sitesKenya
- Study dates
- 10 Mar 2023to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 24 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Kenya4 sites, 4 recruiting
- Recruiting
Homa Bay County Referral Hospital
Homa Bay
- Recruiting
Isebania Sub-County Hospital
Isibania
- Recruiting
Kisii Teaching and Referral Hospital
Kisii
- Recruiting
Rongo Sub-County Hospital
Rongo
About this study
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.
Read the detailed description
Current diarrhea management strategies in low- and middle-income countries (oral rehydration solution, ReSoMal and zinc) focus primarily on the management of dehydration and micronutrient replacement and appear to have negligible impact in preventing future diarrheal episodes or improving nutritional outcomes. Lactoferrin and lysozyme are milk-derived nutritional supplements that may reduce the risk of diarrheal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function. Children with moderate or severe wasting are at particularly high-risk of death, diarrhea recurrence, and nutritional deterioration following a diarrheal episode. This factorial, double-blind, placebo-controlled, randomized trial aims to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhea incidence and improving nutritional recovery in children convalescing from diarrhea and wasting. We will explore whether these interventions improve outcomes by reducing enteric pathogens, improving enteric function and/or increasing hemoglobin concentrations in these children. This study aims to enroll 600 Kenyan children aged 6-24 months from facilities in Western Kenya. Enrolled children will be randomized to 16-weeks of lactoferrin, lysozyme, a combination of the two, or placebo and be followed up for 24 weeks total, with bi-weekly home visits by community health workers and clinic visits at 4, 10, 16, and 24 weeks. Results of this study will inform management strategies for children with moderate/severe wasting at high risk for mortality, morbidity, and nutritional deterioration following diarrhea.
Aim 1: To determine whether a 16-week course of lactoferrin, lysozyme or a combination of both shortens time to WHO-defined recovery from wasting (MUAC ≥12.5cm) and reduces the incidence of moderate-to-severe diarrhea during the subsequent 6-months following presentation to a health facility with diarrhea among children with moderate/severe childhood wasting (MUAC <12.5 cm at the time of screening).
Hypothesis: Children randomized to lactoferrin, lysozyme, or the combination of both will experience a lower incidence of moderate-to-severe diarrhea and an earlier recovery from wasting (increased MUAC) over the subsequent 6-months than placebo-treated children. Combination therapy will provide synergistic benefit in reducing diarrhea and improving nutritional recovery.
Aim 2: To explore whether a 16-week course of lactoferrin, lysozyme or combination therapy improves secondary clinical, nutritional, enteric pathogen, and enteric function outcomes.
Hypothesis: Children randomized to lactoferrin, lysozyme, or the combination will experience fewer hospitalizations and deaths, improved linear growth, a reduced prevalence of specific enteric bacteria associated with linear growth failure (Campylobacter, LT-ETEC, EAEC, typical EPEC and/or Shigella), improved markers of enteric dysfunction (myeloperoxidase, alpha antitrypsin, neopterin, and the lactulose:rhamnose ratio) and improved hemoglobin, as compared to placebo-treated children.
Aim 3: To evaluate acceptability, adherence and cost-effectiveness of lactoferrin and/or lysozyme in Kenya.
Hypothesis: Both therapies will be highly acceptable to caregivers and health workers. Adherence to the therapies will be high among participants (≥ 95%). Lactoferrin and lysozyme, alone and in combination, will be more cost-effective interventions for reducing moderate-to-severe diarrhea in the short-term as compared to the standard-of-care.
- Conditions
- Diarrhea, Wasting, Malnutrition, Child
- Being tested
- Lactoferrin, Lysozyme, Lactoferrin + Lysozyme, Placebo
- Medical subject headings
- Diarrhea, Cachexia, Child Nutrition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LactoferrinDietary 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.
LysozymeDietary supplement
Caregivers of children will be instructed to provide 41.5g of Lysosure daily mixed with 125 mL of porridge or other complimentary food.
Lactoferrin + LysozymeCombination 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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Lactoferrin Arm | Experimental | 16-week course of lactoferrin Receives: Dietary Supplement: Lactoferrin |
| Lysozyme Arm | Experimental | 16-week course of lysozyme Receives: Dietary Supplement: Lysozyme |
| Combination Arm (Lactoferrin + Lysozyme) | Experimental | 16-week course of lactoferrin and lysozyme Receives: Combination Product: Lactoferrin + Lysozyme |
| Placebo Arm | Placebo comparator | 16-week course of taste/appearance-matched placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 6 months
Secondary outcomes (23)
Incidence of diarrhea (any severity)
Diarrhea (any severity) will be defined as diarrhea (3 or more abnormally loose or watery stool) during follow-up, irrespective of severity, ascertained through follow-up visit questionnaires and a diarrhea diary. Episodes will be defined as per the primary outcome.
Measured: 6 months
Incidence of severe diarrhea
Severe diarrhea defined by the CODA diarrhea severity score of 7 or more or dysentery. Episodes will be defined as per the primary outcome.
Measured: 6 months
Incidence of dysentery
Dysentery will be defined as evidence or reported visible blood in stool. Episodes will be defined as per the primary outcome.
Measured: 6 months
Incidence of medically-attended diarrhea
Medically-attended diarrhea will be defined as diarrhea that led to an outpatient or inpatient visit at a health facility or hospital that is typically attended by a nurse, clinical officer, and/or physician. Episodes will be defined as per the primary outcome.
Measured: 6 months
Cumulative duration of diarrhea
Defined as cumulative days of diarrhea ascertained from follow-up visit questionnaires and a diarrhea diary, irrespective of episodes
Measured: 6 months
Proportion of children who recovered from wasting based on two consecutive MUAC measurements ≥12.5 at any point during the follow-up period.
Measured: 6 months
Incidence of hospitalization
Defined as any inpatient admission that results in an overnight stay (irrespective of diagnosis) in a health-facility and time to hospitalization or death analyzed as a combined outcome
Measured: 6 months
Composite outcome of time to hospitalization and death
Hospitalization will be defined as any inpatient admission that results in an overnight stay (irrespective of diagnosis) in a health-facility
Measured: 6 months
Hemoglobin concentration
Will be determined at week 16
Measured: Measured at week 16
Change in length for age z-score (linear growth)
Growth that includes length and weight measurements at each time point will be used to create age-standardized z-scores, calculated using WHO-established reference standards and the WHO ANTHRO software. Linear growth will be defined as change (Δ) in LAZ.
Measured: 6 months
Change in weight for length z-score
Growth that includes length and weight measurements at each time point will be used to create age-standardized z-scores, calculated using WHO-established reference standards and the WHO ANTHRO software. Ponderal growth will be defined as change (Δ) in weight for length z-score (WLZ) and Δ MUAC.
Measured: 6 months
Change in mid-upper arm circumference (cm)
Growth that includes length and weight measurements at each time point will be used to create age-standardized z-scores, calculated using WHO-established reference standards and the WHO ANTHRO software. Ponderal growth will be defined as change (Δ) in weight for length z-score (WLZ) and Δ MUAC.
Measured: 6 months
Concentration of fecal alpha antitrypsin (mg/g)
Fecal biomarker of enteric function
Measured: Measured at baseline, week 4, 16, and 24
Concentration of fecal myeloperoxidase (ng/mL)
Fecal biomarker of enteric function
Measured: Measured at baseline, week 4, 16, and 24
Concentration of fecal calprotectin (mcg/g)
Fecal biomarker of enteric function
Measured: Measured at baseline, week 4, 16, and 24
Lactulose:rhamnose ratio
Lactulose:rhamnose ratio is a functional assessment of enteric integrity. Ratio will be measured in subset of 50 children per arm (200 children total).
Measured: Measured at week 4, 10, 16, and 24 for a subset of 200 participants (50 per arm)
Proportion of participants with enteric infections
Determined by qPCR at or below the minimum limit of detection (cycle thresholds [CT] <35)
Measured: Measured at week 4 for all participants and at week 16 and 24 for a subset of 200 participants (50 per arm)
Proportion of caregivers reporting that administration of lactoferrin and/or lysozyme was desirable or satisfactory via 5-point Likert scale responses in surveys and focus group discussions (FGDs)
Acceptability measure
Measured: Week 4, 10, 16 (surveys) and 6 months (FGDs)
Proportion of caregivers reporting perceived trust, safety, and comfort in administering lactoferrin and/or lysozyme via 5-point Likert scale responses in surveys and focus group discussions (FGDs)
Acceptability measure
Measured: Week 16 (surveys) and 6 months (FGDs)
Proportion of caregivers self-reporting their child consumed some or all of the investigational product ≥95% of the time using daily pictorial logs
Adherence measure
Measured: 16 weeks
Proportion of children adherent to the recommended dosing based on objectively measured container consumption (± 10% consumption of prescribed IP in all weeks)
Adherence measure
Measured: 16 weeks
Incremental costs of diarrhea
Incremental costs of diarrhea will be measured in each arm and compared to the placebo arm
Measured: 6 months
Cost-per-episode of diarrhea averted
Cost-per-episode of diarrhea averted will be measured in each arm and compared to the placebo arm
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2022
- Study start10 Mar 2023
- Primary completionJul 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Patricia B Pavlinac, University of Washington
- Investigators
- Patricia B Pavlinac, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05519254
- Sponsor's protocol ID
- STUDY00011759
- Other IDs
- 1R01HD103642-01
- Status last verified
- Aug 2025
- First submitted
- 3 Aug 2022
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified analytic dataset and analytic R code will be made publicly available.
Publications
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.
PubMed 23746772Tickell 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.
PubMed 29140236Talbert 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.
PubMed 30686268Tickell 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.
PubMed 31981554Brander 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.
PubMed 31767012Cheng 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.
PubMed 30829679Ochoa 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.
PubMed 22939927Zavaleta 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.
PubMed 17255841Tiwari 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.
PubMed 39122384
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lactoferrin and Lysozyme Supplementation for Long-term Diarrhea Sequelae
- ClinicalTrials.gov ID
- NCT05519254
- Acronym / sponsor ID
- STUDY00011759
- Conditions
- Diarrhea, Wasting, Malnutrition, Child
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Current diarrhea management strategies in low- and middle-income countries (oral rehydration solution, ReSoMal and zinc) focus primarily on the management of dehydration and micronutrient replacement and appear to have negligible impact in preventing future diarrheal episodes or improving nutritional outcomes. Lactoferrin and lysozyme are milk-derived nutritional supplements that may reduce the risk of diarrheal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function. Children with moderate or severe wasting are at particularly high-risk of death, diarrhea recurrence, and nutritional deterioration following a diarrheal episode. This factorial, double-blind, placebo-controlled, randomized trial aims to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhea incidence and improving nutritional recovery in children convalescing from diarrhea and wasting. We will explore whether these interventions improve outcomes by reducing enteric pathogens, improving enteric function and/or increasing hemoglobin concentrations in these children. This study aims to enroll 600 Kenyan children aged 6-24 months from facilities in Western Kenya. Enrolled children will be randomized to 16-weeks of lactoferrin, lysozyme, a combination of the two, or placebo and be followed up for 24 weeks total, with bi-weekly home visits by community health workers and clinic visits at 4, 10, 16, and 24 weeks. Results of this study will inform management strategies for children with moderate/severe wasting at high risk for mortality, morbidity, and nutritional deterioration following diarrhea.
Aim 1: To determine whether a 16-week course of lactoferrin, lysozyme or a combination of both shortens time to WHO-defined recovery from wasting (MUAC ≥12.5cm) and reduces the incidence of moderate-to-severe diarrhea during the subsequent 6-months following presentation to a health facility with diarrhea among children with moderate/severe childhood wasting (MUAC <12.5 cm at the time of screening).
Hypothesis: Children randomized to lactoferrin, lysozyme, or the combination of both will experience a lower incidence of moderate-to-severe diarrhea and an earlier recovery from wasting (increased MUAC) over the subsequent 6-months than placebo-treated children. Combination therapy will provide synergistic benefit in reducing diarrhea and improving nutritional recovery.
Aim 2: To explore whether a 16-week course of lactoferrin, lysozyme or combination therapy improves secondary clinical, nutritional, enteric pathogen, and enteric function outcomes.
Hypothesis: Children randomized to lactoferrin, lysozyme, or the combination will experience fewer hospitalizations and deaths, improved linear growth, a reduced prevalence of specific enteric bacteria associated with linear growth failure (Campylobacter, LT-ETEC, EAEC, typical EPEC and/or Shigella), improved markers of enteric dysfunction (myeloperoxidase, alpha antitrypsin, neopterin, and the lactulose:rhamnose ratio) and improved hemoglobin, as compared to placebo-treated children.
Aim 3: To evaluate acceptability, adherence and cost-effectiveness of lactoferrin and/or lysozyme in Kenya.
Hypothesis: Both therapies will be highly acceptable to caregivers and health workers. Adherence to the therapies will be high among participants (≥ 95%). Lactoferrin and lysozyme, alone and in combination, will be more cost-effective interventions for reducing moderate-to-severe diarrhea in the short-term as compared to the standard-of-care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lactoferrin Arm | Experimental | Dietary Supplement: Lactoferrin16-week course of lactoferrin |
| Lysozyme Arm | Experimental | Dietary Supplement: Lysozyme16-week course of lysozyme |
| Combination Arm (Lactoferrin + Lysozyme) | Experimental | Combination Product: Lactoferrin + Lysozyme16-week course of lactoferrin and lysozyme |
| Placebo Arm | Placebo comparator | Other: Placebo16-week course of taste/appearance-matched placebo |
Who may qualify
- Ages
- 6 to 24 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LactoferrinCaregivers 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. | Dietary supplement | Lactoferrin Arm |
| LysozymeCaregivers of children will be instructed to provide 41.5g of Lysosure daily mixed with 125 mL of porridge or other complimentary food. | Dietary supplement | Lysozyme Arm |
| Lactoferrin + LysozymeCaregivers 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 product | Combination Arm (Lactoferrin + Lysozyme) |
| PlaceboCaregivers 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. | Other | Placebo Arm |
Primary outcome
Incidence of moderate-to-severe diarrhea
Time frame: 6 months
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).
Time to nutritional recovery
Time frame: 6 months
Defined as the number of days since enrollment to the date of the second of two consecutive MUAC measurements ≥ 12.5 cm.
23 secondary outcomes
Incidence of diarrhea (any severity)
Time frame: 6 months
Incidence of severe diarrhea
Time frame: 6 months
Incidence of dysentery
Time frame: 6 months
Incidence of medically-attended diarrhea
Time frame: 6 months
Cumulative duration of diarrhea
Time frame: 6 months
Proportion of children who recovered from wasting based on two consecutive MUAC measurements ≥12.5 at any point during the follow-up period.
Time frame: 6 months
Incidence of hospitalization
Time frame: 6 months
Composite outcome of time to hospitalization and death
Time frame: 6 months
Hemoglobin concentration
Time frame: Measured at week 16
Change in length for age z-score (linear growth)
Time frame: 6 months
Change in weight for length z-score
Time frame: 6 months
Change in mid-upper arm circumference (cm)
Time frame: 6 months
Concentration of fecal alpha antitrypsin (mg/g)
Time frame: Measured at baseline, week 4, 16, and 24
Concentration of fecal myeloperoxidase (ng/mL)
Time frame: Measured at baseline, week 4, 16, and 24
Concentration of fecal calprotectin (mcg/g)
Time frame: Measured at baseline, week 4, 16, and 24
Lactulose:rhamnose ratio
Time frame: Measured at week 4, 10, 16, and 24 for a subset of 200 participants (50 per arm)
Proportion of participants with enteric infections
Time frame: Measured at week 4 for all participants and at week 16 and 24 for a subset of 200 participants (50 per arm)
Proportion of caregivers reporting that administration of lactoferrin and/or lysozyme was desirable or satisfactory via 5-point Likert scale responses in surveys and focus group discussions (FGDs)
Time frame: Week 4, 10, 16 (surveys) and 6 months (FGDs)
Proportion of caregivers reporting perceived trust, safety, and comfort in administering lactoferrin and/or lysozyme via 5-point Likert scale responses in surveys and focus group discussions (FGDs)
Time frame: Week 16 (surveys) and 6 months (FGDs)
Proportion of caregivers self-reporting their child consumed some or all of the investigational product ≥95% of the time using daily pictorial logs
Time frame: 16 weeks
Proportion of children adherent to the recommended dosing based on objectively measured container consumption (± 10% consumption of prescribed IP in all weeks)
Time frame: 16 weeks
Incremental costs of diarrhea
Time frame: 6 months
Cost-per-episode of diarrhea averted
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Background: PubMed 23746772Black 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.
- Background: PubMed 29140236Tickell 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.
- Background: PubMed 30686268Talbert 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.
- Background: PubMed 31981554Tickell 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.
- Background: PubMed 31767012Brander 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.
- Background: PubMed 30829679Cheng 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.
- Background: PubMed 22939927Ochoa 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.
- Background: PubMed 17255841Zavaleta 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.
- Derived from this study: PubMed 39122384Tiwari 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.
- Individual participant dataSharing planned: Yes. The de-identified analytic dataset and analytic R code will be made publicly available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Patricia B Pavlinac principal investigator
University of Washington
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lactoferrin, Lysozyme and Lactoferrin + Lysozyme in people with Diarrhea and Wasting, run by University of Washington at 4 sites in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruchi Tiwari (2067904389, ruchit@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of moderate-to-severe diarrhea (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05519254, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.