PoliomyelitisNCT04432935
Effect of Lactoferrin on Polio Seroconversion
A study testing Bovine Lactoferrin in people with Poliomyelitis, run by Aga Khan University at 1 site in Pakistan.
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. Read more about this study
- Who is it for?
- Ages 1 hour to 23 hoursHealthy volunteers can take part
- Conditions the study is for
- Poliomyelitis
- What is being tested?
- Bovine Lactoferrin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 468 participants
- Where
- 1 sitePakistan
- Study dates
- 1 Oct 2020to 30 Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 1 hour to 23 hours
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Bovine Lactoferrin on Seroconversion Following Polio Vaccine Administration in Children: A Randomized Control Trial
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.
Read the detailed 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.
- Conditions
- Poliomyelitis
- Being tested
- Bovine Lactoferrin, Placebo Glucon D
- Keywords
- Bovine Lactoferrin, Poliovirus, Routine immunization
- Medical subject headings
- Poliomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bovine LactoferrinDietary supplement
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.
Placebo Glucon DOther
This group will be given 100mg Glucon-D (99.4% glucose) which will be similar in shape, color to the bLF.
| Study group | Role | What they receive |
|---|---|---|
| Bovine Lactoferrin | Experimental | Intervention group will receive bovine lactoferrin supplementation daily once a day from day 0 of birth to 6 weeks of life. Receives: Dietary Supplement: Bovine Lactoferrin |
| Glucon D | Placebo comparator | Control group will receive Glucon-D supplementation daily once a day from day 0 of birth to 6 weeks of life. Receives: Other: Placebo Glucon D |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 10 weeks
Secondary outcomes (3)
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
Measured: 18 weeks
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.
Measured: 19 weeks
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
Measured: 20 and 22 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start1 Oct 2020
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for PoliomyelitisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group 1: Bovine lactoferrin (bLF) will be administered (300mg) from day 0 of birth to 6 weeks of life with a single daily dose mixed with milk (preferentially breast milk otherwise premature formula milk). Group 2: Placebo will be administered from day 0 of birth to 6 weeks of life. (Placebo will be physically identical to the bLF mixed with breast milk or premature formula milk).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 468 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aga Khan University
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Dr Sajid Bashir Soofi, Aga Khan University
- Investigators
- Sajid Soofi, MBBS, FCPS, Principal investigator, Aga Khan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04432935
- Sponsor's protocol ID
- 2019-1955-5013
- Status last verified
- Aug 2023
- First submitted
- 11 Dec 2019
- Last updated
- 16 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal.
Publications
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.
PubMed 27729081Roseanu 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.
PubMed 16754302Seganti 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.
PubMed 15222481Ochoa 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.
PubMed 18472012Superti 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.
PubMed 9403835Hwang 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.
PubMed 17698261Hwang 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.
PubMed 20006305Habib A, Nausheen S, Nooruddin S, Javed T, Samejo T, Hussain A, Namdev S, Amirali S, Umer M, Sheikh L, Hussain I, Ariff S, Soofi S. Effect of bovine lactoferrin on seroconversion following polio vaccine administration in children: protocol for a double-blinded randomised controlled trial. BMJ Open. 2022 May 24;12(5):e050849. doi: 10.1136/bmjopen-2021-050849.
PubMed 35613782
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Bovine Lactoferrin on Seroconversion Following Polio Vaccine Administration in Children: A Randomized Control Trial
- ClinicalTrials.gov ID
- NCT04432935
- Acronym / sponsor ID
- 2019-1955-5013
- Conditions
- Poliomyelitis
- Keywords
- Bovine Lactoferrin, Poliovirus, Routine immunization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 468 participants (actual)
- Lead sponsor
- Aga Khan UniversityUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 16 Jun 2020 (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.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Group 1: Bovine lactoferrin (bLF) will be administered (300mg) from day 0 of birth to 6 weeks of life with a single daily dose mixed with milk (preferentially breast milk otherwise premature formula milk). Group 2: Placebo will be administered from day 0 of birth to 6 weeks of life. (Placebo will be physically identical to the bLF mixed with breast milk or premature formula milk).
| Arm | Type | Receives |
|---|---|---|
| Bovine Lactoferrin | Experimental | Dietary Supplement: Bovine LactoferrinIntervention group will receive bovine lactoferrin supplementation daily once a day from day 0 of birth to 6 weeks of life. |
| Glucon D | Placebo comparator | Other: Placebo Glucon DControl group will receive Glucon-D supplementation daily once a day from day 0 of birth to 6 weeks of life. |
Who may qualify
- Ages
- 1 hour to 23 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| Bovine LactoferrinLactoferrin 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. | Dietary supplement | Bovine Lactoferrin |
| Placebo Glucon DThis group will be given 100mg Glucon-D (99.4% glucose) which will be similar in shape, color to the bLF. | Other | Glucon D |
Primary outcome
Assessment of humoral immunity by seroconversion
Time frame: 10 weeks
Presence of detectable antibodies to poliovirus types 1 and 3 in serum) after receipt of two doses of OPV
3 secondary outcomes
Comparison of humoral immunity represented by seroconversion
Time frame: 18 weeks
Comparison of intestinal immunity represented by shedding of poliovirus types 1 and 3
Time frame: 19 weeks
Comparison of duration of shedding among the two study arms
Time frame: 20 and 22 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2023.
- Background: PubMed 27729081Hussain 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.
- Background: PubMed 16754302Roseanu 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.
- Background: PubMed 15222481Seganti 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.
- Background: PubMed 18472012Ochoa 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.
- Background: PubMed 9403835Superti 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.
- Background: PubMed 17698261Hwang 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.
- Background: PubMed 20006305Hwang 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.
- Derived from this study: PubMed 35613782Habib A, Nausheen S, Nooruddin S, Javed T, Samejo T, Hussain A, Namdev S, Amirali S, Umer M, Sheikh L, Hussain I, Ariff S, Soofi S. Effect of bovine lactoferrin on seroconversion following polio vaccine administration in children: protocol for a double-blinded randomised controlled trial. BMJ Open. 2022 May 24;12(5):e050849. doi: 10.1136/bmjopen-2021-050849.
- Agency Response Letter GRAS Notice No. GRN 000611Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal.
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Poliomyelitis
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. This study is not recruiting at the moment.
Sajid Soofi, MBBS, FCPS principal investigator
Aga Khan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bovine Lactoferrin in people with Poliomyelitis, run by Aga Khan University at 1 site in Pakistan.
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 3 inclusion and 5 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: finished, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of humoral immunity by seroconversion (time frame: 10 weeks). 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 NCT04432935, which also lists 8 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 16 Aug 2023.