Lactoferrin for Prevention of Sepsis in Infants (NEOLACTO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Universidad Peruana Cayetano Heredia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Universidad Peruana Cayetano Heredia
ClinicalTrials.gov Identifier:
NCT01525316
First received: January 30, 2012
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

The investigators propose a clinical trial in premature infants to determine the effect of orally-administered bovine lactoferrin on occurrence of severe infections and to determine whether as a result of decreased infections, infants' growth and development improve after daily lactoferrin supplementation, due to its antimicrobial and anti-inflammatory properties. If successful, the use of lactoferrin as a protective protein could profoundly affect clinical care of neonates both in the developed and developing world.


Condition Intervention Phase
Late Onset Neonatal Sepsis
Dietary Supplement: Bovine Lactoferrin
Dietary Supplement: Maltodextrin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Lactoferrin for Prevention of Sepsis in Infants

Resource links provided by NLM:


Further study details as provided by Universidad Peruana Cayetano Heredia:

Primary Outcome Measures:
  • First episode of late-onset sepsis or sepsis-associated death [ Time Frame: 72hrs to 8 weeks of age ] [ Designated as safety issue: No ]
    The primary study outcome will be a composite outcome of the first episode of late-onset sepsis or sepsis-associated death.


Secondary Outcome Measures:
  • Neurodevelopment [ Time Frame: 12 to 24 months of corrected age ] [ Designated as safety issue: No ]
    Neurodevelopment at 24 months of corrected age, assessed by the Mullen Scale for Early Learning.


Estimated Enrollment: 414
Study Start Date: May 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bovine Lactoferrin
Lactoferrin is a freeze-dried protein purified directly from fresh bovine milk.
Dietary Supplement: Bovine Lactoferrin
Infants will receive oral bovine lactoferrin (200 mg/Kg/day divided in three dosis) for 8 weeks. Lactoferrin will be dissolved in human milk or infant formula or in a 5% glucose solution. Each dose will be dissolved in a small volume so the maximum lactoferrin concentration will be 25mg/mL.
Other Name: Lactoferrin
Placebo Comparator: Maltodextrin
Maltodextrin is an inert sugar.
Dietary Supplement: Maltodextrin
Infants will receive oral maltodextrin (200mg/Kg/day in three divided dosis) for 8 weeks. Maltodextrin will be dissolved in human milk or infant formula or in a 5% glucose solution. Each dose will be dissolved in a small volume so the maximum maltodextrin concentration will be 25mg/mL.

Detailed Description:

Neonatal mortality is an important global public health challenge. Approximately 4 million neonatal deaths per year occur in developing countries, accounting for 40% all of deaths in children under 5. Infection, birth asphyxia and consequences of premature birth/low birth weight are responsible for the majority of these deaths. Although advances in neonatal intensive care led to improved survival of premature infants, sepsis continues to be an important cause of morbidity and mortality worldwide.

Lactoferrin, an iron-binding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is one of the most important proteins present in mammalian milk. Our hypothesis is that lactoferrin given as a daily oral food supplement to preterm infants will improve their health by mimicking its protective role in milk. There is a vast literature showing in vitro and animal model benefits of lactoferrin. However, there are few clinical studies designed to translate this knowledge into patient care. A recent Italian study showed that lactoferrin given to low-birth weight infants reduces incidence of sepsis (17% vs. 6%) and death. Whether lactoferrin has an effect in higher risk populations and an impact on subsequent neurodevelopment and growth remains to be determined.

Specific aim 1: The investigators will test the hypothesis that bovine lactoferrin supplementation prevents serious infections in preterm infants. The investigators will conduct a randomized placebo-controlled double blind study in 414 premature infants < 2000 g in Neonatal Units in Lima, Peru to determine whether bovine lactoferrin prevents late-onset sepsis or sepsis-associated death.

This hypothesis is based on lactoferrin´s antimicrobial and immunomodulating activities. Lactoferrin protects against pathogens in multiple ways: it sequesters iron essential for bacterial growth; binds to lipopolysaccharide (LPS) on the cell surface of Gram negative bacteria, disrupting the bacterial cell membrane; it has anti-lipoteichoic acid (against Gram positive organisms) and anti-Candida cell wall activities. The investigators have found that lactoferrin not only inhibits growth; it impairs virulence of some of the major pathogens by decreasing their ability to adhere or to invade mammalian cells, and by binding to, or degrading, specific virulence proteins. Lactoferrin may protect infants from sepsis by blocking attachment and invasion of organisms in the gut.

Specific aim 2: The investigators will test the hypothesis that bovine lactoferrin supplementation promotes better neurodevelopment and growth outcomes in preterm infants assessed by the Mullen Scales of Early Learning, a standardized neurologic exam and growth measurements at 12, 18 and 24 months corrected age.

It is postulated that exposure of the preterm brain to inflammatory mediators during infectious episodes contribute to brain (white matter) injury and poor developmental outcome. It has been demonstrated that breast milk has a beneficial effect on neurodevelopment outcomes in preterm infants. The investigators hypothesize that lactoferrin is the major factor in milk responsible for this effect due to its antimicrobial and immunomodulatory properties: it reduces inflammation by decreasing production of tumor necrosis factor α and other pro-inflammatory molecules, and by regulating the immune response, protecting against severe inflammation related to infection and septic shock. In addition, the investigators hypothesize that lactoferrin will improve growth by decreasing the frequency of growth-impairing infections and by lactoferrin effect on intestinal cell proliferation, differentiation and maturation.

The use of lactoferrin as a broad-spectrum non-pathogen specific antimicrobial protective protein is an innovative approach. If successful this study will profoundly affect clinical care of neonates both in the developed and developing world.

  Eligibility

Ages Eligible for Study:   up to 72 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates with a birth weight between 500g and 2000g
  • Neonates born in, or referred to the Neonatal Intermediate and Intensive Care Units of one of the participating hospitals in the first 72 hours of life.

Exclusion Criteria:

  • Neonates with underlying gastrointestinal problems that prevent oral intake.
  • Neonates with predisposing conditions that profoundly affect growth and development (chromosomal abnormalities, structural brain anomalies, severe congenital abnormalities).
  • Neonates who have a family history of cow milk allergy.
  • Neonates that, according to the investigator criteria, will not have the chance to complete the subsequent study visits (patients that before one month old would not be living in Lima).
  • Neonates whose parents decline to participate.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525316

Contacts
Contact: Theresa J Ochoa, MD 0051-1-482-3910 ext 20 theresa.j.ochoa@uth.tmc.edu
Contact: Thomas G Cleary, MD 001 713-702-2860 thomas.g.cleary@uth.tmc.edu

Locations
Peru
Hospital Nacional Cayetano Heredia Recruiting
Lima, Peru, 0511
Contact: Jaime Zegarra, MD    51-1-999708745    jaime.zegarra@upch.pe   
Contact: Sicilia Bellomo, MD    51-1-999198387    siciliabellomo@gmail.com   
Principal Investigator: Jaime Zegarra, MD         
Sub-Investigator: Sicilia Bellomo, MD         
Sub-Investigator: María Luz Rospigliosi, MD         
Sub-Investigator: Geraldine Borda, MD         
Hospital Nacional Guillermo Almenara Irigoyen Recruiting
Lima, Peru, 0511
Contact: Anne Castañeda, MD    51-1-998411906    casfuentes@hotmail.com   
Contact: Oscar Chumbes, MD    51-1-942760638    racso140@hotmail.com   
Principal Investigator: Anne Castañeda, MD         
Sub-Investigator: Oscar Chumbes, MD         
Sub-Investigator: Liliana Cuba, MD         
Hospital Nacional Alberto Sabogal Sologuren Recruiting
Lima, Peru, 0511
Contact: Luis Cam, MD    51-1-999652544    drluiscam@yahoo.com   
Contact: Ana Lino, MD    51-1-997915925    analino31@yahoo.com   
Principal Investigator: Luis Cam, MD         
Sub-Investigator: Ana Lino, MD         
Sub-Investigator: Augusto Cama, MD         
Sponsors and Collaborators
Universidad Peruana Cayetano Heredia
Investigators
Principal Investigator: Theresa J Ochoa, MD Universidad Peruana Cayetano Heredia
  More Information

Publications:
Responsible Party: Universidad Peruana Cayetano Heredia
ClinicalTrials.gov Identifier: NCT01525316     History of Changes
Other Study ID Numbers: SIDISI 57710, 1R01HD067694-01A1
Study First Received: January 30, 2012
Last Updated: December 12, 2013
Health Authority: Peru: Instituto Nacional de Salud

Keywords provided by Universidad Peruana Cayetano Heredia:
Late Onset Neonatal Sepsis
Neonates
Lactoferrin
Infections
Prevention
Neurodevelopment

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Lactoferrin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014