Effect of Lactoferrin on Polio Seroconversion

Poliomyelitis Clinical Trial

Official title:

Effect of Bovine Lactoferrin on Seroconversion Following Polio Vaccine Administration in Children: A Randomized Control Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04432935
• Other study ID #: 2019-1955-5013
• Status: Completed
• Phase: N/A
• Start date: October 1, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2023
• Source: Aga Khan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A massive decline in cases of poliomyelitis was observed worldwide since 1988; however its transmission continues in Pakistan and Afghanistan. In 2017, a total of 17 cases were reported from these countries, which represent approximately half of the cases reported in 2016. This achievement was made possible by large scale use of oral polio vaccine (OPV) and inactivated polio vaccine (IPV). Despite vigorous efforts to end poliovirus transmission in endemic areas, several challenges including illiteracy, poverty, malnutrition, difficulty to access health and immunization services adversely affect the effectiveness of the polio eradication efforts. Innovations are thus needed to accomplish the goal of eradication as due to limited funding, the sustainability of a program becomes questionable. The aim of this study is to assess the effectiveness of lactoferrin in increasing mucosal and serum immunity in children following administration of poliovirus vaccines.

Description:

Lactoferrin was first discovered in bovine milk which was later isolated in human milk as the second most abundant protein; with high levels found in colostrum. Evidence suggests that Lactoferrin enhances a child's immunity against gastrointestinal infections by inhibiting the growth of bacteria through iron deprivation and by preventing attachment of the virus to the intestinal cells thus children become less susceptible to virus replication in the gut. Investigations of enhanced efficacy of the BCG (Bacillus Calmette-Guérin) vaccine after administration of Lactoferrin showed promising results. The use of bovine Lactoferrin in children is generally recognized as safe by the US Food and Drug Administration. Its anti-infective properties creates a new window of opportunity to assess its effects on the level of seroconversion following poliovirus vaccination in children.

This is a double-blinded two arm randomized placebo-controlled trial. A total of 377 neonates will be enrolled in each group (754 neonates in both groups). Females ages 18-45 years in their last trimester of pregnancy in Karachi, Pakistan will be recruited for the study by the study team and consent will be obtained. Participants will be newborns (on day 1 of birth) who will be followed through 6 months of age. Newborns who fulfill the inclusion criteria will be randomly assigned to the control or intervention group in 1:1 ratio on the first day of birth. Intervention group will receive a daily bovine lactoferrin supplementation whereas Control group will receive a daily placebo supplementation along with breast milk from day 0 of birth to 6 weeks of life. Newborns will be followed up daily during the course of the hospital stay.

After discharge from the hospital, mothers will be provided with a week's supply of lactoferrin or placebo along with instructions on how and when to administer it to the baby. Newborns will be followed up weekly. Compliance will be assessed by counting the used sachets of lactoferrin or placebo because mothers will be instructed to keep the empty sachets in a dedicated container issued by study staff. Mothers will be strictly advised to administer all vaccinations according to the routine immunization schedule. For both groups, a blood sample will be collected in the hospital and containers will be given to the mother for collections of stool for the newborn.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 468
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Hour to 23 Hours

Eligibility

Inclusion Criteria:

• Pregnant females aged 18 to 45 years with no underlying complications or co-morbidities

• Residence less than 30 kms away from the study clinic and have resided there for at least 1 year. Family MUST indicate that they will not move from their current residence for the 5 months after birth of the child (study period)

• Healthy singleton full-term births born to these mothers, regardless of birth weight and an APGAR score of 7 or higher 5 minutes after delivery with no underlying complication (randomization will take place at this stage)

Exclusion Criteria:

• Females with health issues and high risk pregnancies

• Neonates presenting with any morbidities and congenital anomalies will be excluded from the study

• Preterm birth (<37 weeks of gestation)

• Immunodeficiency disorder in immediate family member

• Parents refusing to consent

Related Conditions & MeSH terms

• Poliomyelitis

Intervention

Dietary Supplement:
• Bovine Lactoferrin
Lactoferrin is a nutritional supplement which was first discovered in bovine milk which was later isolated in human milk as the second most abundant protein; with high levels found in colostrum. The use of bovine Lactoferrin in children is generally recognized as safe by the US Food and Drug Administration.

Other:
• Placebo Glucon D
This group will be given 100mg Glucon-D (99.4% glucose) which will be similar in shape, color to the bLF.

Locations

Country	Name	City	State
Pakistan	Kharadar Campus, Aga Khan University Hospital	Karachi

Sponsors (2)

Lead Sponsor	Collaborator
Aga Khan University	Centers for Disease Control and Prevention

Country where clinical trial is conducted

Pakistan, 

References & Publications (7)

Hussain SF, Boyle P, Patel P, Sullivan R. Eradicating polio in Pakistan: an analysis of the challenges and solutions to this security and health issue. Global Health. 2016 Oct 12;12(1):63. doi: 10.1186/s12992-016-0195-3. — View Citation

Hwang SA, Arora R, Kruzel ML, Actor JK. Lactoferrin enhances efficacy of the BCG vaccine: comparison between two inbred mice strains (C57BL/6 and BALB/c). Tuberculosis (Edinb). 2009 Dec;89 Suppl 1:S49-54. doi: 10.1016/S1472-9792(09)70012-5. — View Citation

Hwang SA, Wilk KM, Budnicka M, Olsen M, Bangale YA, Hunter RL, Kruzel ML, Actor JK. Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis. Vaccine. 2007 Sep 17;25(37-38):6730-43. doi: 10.1016/j.vaccine.2007.07.005. Epub 2007 Jul 27. — View Citation

Ochoa TJ, Cleary TG. Effect of lactoferrin on enteric pathogens. Biochimie. 2009 Jan;91(1):30-4. doi: 10.1016/j.biochi.2008.04.006. Epub 2008 Apr 18. — View Citation

Roseanu A, Brock JH. What are the structure and the biological function of lactoferrin in human breast milk? IUBMB Life. 2006 Apr;58(4):235-7. doi: 10.1080/15216540600577897. No abstract available. — View Citation

Seganti L, Di Biase AM, Marchetti M, Pietrantoni A, Tinari A, Superti F. Antiviral activity of lactoferrin towards naked viruses. Biometals. 2004 Jun;17(3):295-9. doi: 10.1023/b:biom.0000027708.27142.bc. — View Citation

Superti F, Ammendolia MG, Valenti P, Seganti L. Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29. Med Microbiol Immunol. 1997 Oct;186(2-3):83-91. doi: 10.1007/s004300050049. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of humoral immunity by seroconversion	Presence of detectable antibodies to poliovirus types 1 and 3 in serum) after receipt of two doses of OPV	10 weeks
Secondary	Comparison of humoral immunity represented by seroconversion	Presence of detectable antibodies to poliovirus types 1, 2 and 3 in serum) after completion of the routine immunization doses/schedule	18 weeks
Secondary	Comparison of intestinal immunity represented by shedding of poliovirus types 1 and 3	If lactoferrin is effective in improving intestinal immunity, shedding is expected to be lower in the lactoferrin receiving group.	19 weeks
Secondary	Comparison of duration of shedding among the two study arms	Represented by shedding at 20 weeks of age and at 22 weeks of age after the challenge dose of bOPV administered	20 and 22 weeks

External Links

•   Agency Response Letter GRAS Notice No. GRN 000611