Immunity to Oral Rotavirus VaccinePhase 4NCT01616693
Zinc and/or Probiotic Supplementation of Rotavirus and Oral Polio Virus Vaccines
A Phase 4 study testing Probiotic, Zinc and Rotavirus vaccine in people with Immunity to Oral Rotavirus Vaccine and Immunity to Oral Polio Vaccine, run by PATH at 1 site in India.
Trial summary
Background: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. Read more about this study
- Who is it for?
- Ages 5 to 16 weeksHealthy volunteers can take part
- Conditions the study is for
- Immunity to Oral Rotavirus Vaccine, Immunity to Oral Polio Vaccine, Shedding of Oral Rotavirus Vaccine
- What is being tested?
- Probiotic, Zinc and Rotavirus vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 620 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2012to Jul 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 5 to 16 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Infants 35-41 days old
- Live in area under surveillance
- Current weight ≥3.2 kg
- No syndromic evidence of immunocompromise as determined by medical doctor
- No prior illness requiring hospitalization
- No current medical condition as determined by medical doctor which precludes study involvement
- Available for follow up for duration of study (through approximately 14 weeks of age)
- Parents/guardians of infant are able to understand and follow study procedures and agree to participate in the study by providing signed informed consent
Who cannot join
- Child has history of atopic symptoms
- Child has a known digestive system defect
- Child has history of chronic diarrhea
- Child has major congenital anomalies
- Child has received a prior dose of rotavirus vaccine
- Child has received a prior dose of polio vaccine (beyond the birth dose)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Supplementation With Zinc and/or Probiotics to Enhance the Immune Response of Oral Rotavirus and Polio Vaccines in Indian Infants
Background: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function.
This study enrolled infants 5 weeks old living in urban Vellore, India to assess the effects of daily zinc (5 mg), probiotic (1010 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix,GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Probiotics and zinc (or placebo) were provided for six weeks. A single dose of test product was administered daily one week prior to first study dose of rotavirus and polio vaccines through 1 week following second study dose of rotavirus and polio vaccines.
Read the detailed description
Co- Primary objectives:
- To evaluate the serologic immune response to rotavirus vaccine (sero-conversion or four-fold rise in rotavirus immunoglobulin A (IgA) antibodies) among Indian infants receiving zinc supplementation given daily for a week prior to the administration of the first dose through a week following the second dose of oral rotavirus vaccine compared to those receiving a zinc placebo.
- To evaluate the serologic immune response to rotavirus vaccine (sero-conversion or four-fold rise in rotavirus IgA antibodies) among Indian infants receiving probiotic supplementation given daily for a week prior to the administration of the first dose through a week following the second dose of oral rotavirus vaccine compared to those receiving a probiotic placebo.
- Conditions
- Immunity to Oral Rotavirus Vaccine, Immunity to Oral Polio Vaccine, Shedding of Oral Rotavirus Vaccine
- Being tested
- Probiotic, Zinc, Probiotic placebo, Zinc placebo, Rotavirus vaccine
- Keywords
- rotavirus, polio, zinc supplement, probiotic supplement, rotavirus vaccine shedding
- Medical subject headings
- Poliomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary supplement
Also called Culturelle
A capsule that contains at least 1 x 10^9 Lactobacillus rhamnosus GG organisms per capsule. The contents of this capsule were given once daily orally.
ZincDietary supplement
Zinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally.
Probiotic placeboDietary supplement
The probiotic placebo was manufactured by the same company that manufactured the probiotic and contained inulin powder but no Lactobacillus rhamnosus GG. The contents of the capsule were given once daily orally.
Zinc placeboDietary supplement
The zinc placebo excluded the zinc sulphate but contained lactose and was diluted to match the taste. 5 ml of this suspension was given orally once daily.
Rotavirus vaccineBiological
Also called Rotarix®
1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
Oral polio vaccineBiological
Also called Biopolio®
A liquid trivalent polio vaccine provided orally at 6 and 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Zinc and probiotic | Experimental | Received daily zinc and probiotic supplements, in addition to rotavirus vaccine and trivalent oral polio vaccines. Receives: Dietary Supplement: Probiotic; Dietary Supplement: Zinc; Biological: Rotavirus vaccine; Biological: Oral polio vaccine |
| Zinc alone | Active comparator | Received daily zinc and probiotic placebo supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine. Receives: Dietary Supplement: Zinc; Dietary Supplement: Probiotic placebo; Biological: Rotavirus vaccine; Biological: Oral polio vaccine |
| Probiotic alone | Active comparator | Received daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine. Receives: Dietary Supplement: Probiotic; Dietary Supplement: Zinc placebo; Biological: Rotavirus vaccine; Biological: Oral polio vaccine |
| Placebo | Placebo comparator | Received daily zinc placebo and probiotic placebo, in addition to rotavirus vaccine and trivalent oral polio vaccine. Receives: Dietary Supplement: Probiotic placebo; Dietary Supplement: Zinc placebo; Biological: Rotavirus vaccine; Biological: Oral polio vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine
Defined as an increase in serum anti-rotavirus (RV) VP6 IgA antibodies consistent with seroconversion (detection of serum anti-RV VP6 immunoglobulin A (IgA) antibodies at a concentration ≥20 U/ml in a previously seronegative individual) or a fourfold rise in anti-RV VP6 IgA antibodies between baseline and 14 weeks of age.
Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age).
Measured: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine
Geometric Mean Concentration of Rotavirus-specific IgA
Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus was administered (14 weeks of age).
Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age).
Measured: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine
Secondary outcomes (4)
Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV)
A serologic immune response to OPV is defined as a neutralizing antibody titer to polio virus subtype 3 greater than or equal to 1:8 at 14 weeks of age. This antigen will be used as a conservative estimate because it gives the lowest immune response of all three polio antigens.
Pre-vaccination blood samples were taken when the subject received the first dose of OPV vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of OPV was administered (14 weeks of age).
Measured: from first dose of OPV to 4 weeks after last dose of OPV
Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1
Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by Real-time polymerase chain reaction (RT-PCR). Stool samples were collected on Day 0 (i.e., day of vaccination or -1), Day 4 (±1) and Day 7 (-1 to +2) post vaccination.
Measured: 0, 4 and/or 7 day post dose 1 of rotavirus vaccine
Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2
Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by RT-PCR. Stool samples were collected on Day 0 (i.e., day of vaccination or -1), Day 4 (±1) and Day 7 (-1 to +2) post vaccination.
Measured: 0, 4 and/or 7 day post dose 2 of rotavirus vaccine
Serious Adverse Events (SAEs)
Field workers documented information on SAEs through the duration of the study during home visits (twice weekly between study clinic visits) or SAEs were documented by study clinicians at the study clinic or hospital. All SAEs occurring at any time during the study were recorded on a SAE Form and were reviewed and evaluated by a study clinician and the local IRB. The relationship of the SAE to study vaccine was evaluated and recorded and reported to the local institutional review board (IRB). All SAEs were followed until satisfactory resolution.
Measured: from first day of study to 4 weeks after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Immunity to Oral Rotavirus VaccineStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 620 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- Christian Medical College, Vellore, India, Ministry of Science and Technology, India
- Responsible party
- Sponsor
- Investigators
- Gagandeep Kang, MD, PhD, Principal investigator, Christian Medical Center, Vellore, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01616693
- Sponsor's protocol ID
- CMC ZP 2012; PATH HS-658
- Status last verified
- Dec 2018
- First submitted
- 6 Jun 2012
- Last updated
- 26 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplementation With Zinc and/or Probiotics to Enhance the Immune Response of Oral Rotavirus and Polio Vaccines in Indian Infants
- ClinicalTrials.gov ID
- NCT01616693
- Acronym / sponsor ID
- CMC ZP 2012; PATH HS-658
- Conditions
- Immunity to Oral Rotavirus Vaccine, Immunity to Oral Polio Vaccine, Shedding of Oral Rotavirus Vaccine
- Keywords
- rotavirus, polio, zinc supplement, probiotic supplement, rotavirus vaccine shedding
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 620 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- Christian Medical College, Vellore, India, Ministry of Science and Technology, India
- Study start
- Jul 2012
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 12 Jun 2012 (estimated)
- Results
- Posted 30 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function.
This study enrolled infants 5 weeks old living in urban Vellore, India to assess the effects of daily zinc (5 mg), probiotic (1010 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix,GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Probiotics and zinc (or placebo) were provided for six weeks. A single dose of test product was administered daily one week prior to first study dose of rotavirus and polio vaccines through 1 week following second study dose of rotavirus and polio vaccines.
Detailed description
Co- Primary objectives:
- To evaluate the serologic immune response to rotavirus vaccine (sero-conversion or four-fold rise in rotavirus immunoglobulin A (IgA) antibodies) among Indian infants receiving zinc supplementation given daily for a week prior to the administration of the first dose through a week following the second dose of oral rotavirus vaccine compared to those receiving a zinc placebo.
- To evaluate the serologic immune response to rotavirus vaccine (sero-conversion or four-fold rise in rotavirus IgA antibodies) among Indian infants receiving probiotic supplementation given daily for a week prior to the administration of the first dose through a week following the second dose of oral rotavirus vaccine compared to those receiving a probiotic placebo.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Zinc and probiotic | Experimental | Dietary Supplement: Probiotic, Dietary Supplement: Zinc, Biological: Rotavirus vaccine, Biological: Oral polio vaccineReceived daily zinc and probiotic supplements, in addition to rotavirus vaccine and trivalent oral polio vaccines. |
| Zinc alone | Active comparator | Dietary Supplement: Zinc, Dietary Supplement: Probiotic placebo, Biological: Rotavirus vaccine, Biological: Oral polio vaccineReceived daily zinc and probiotic placebo supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine. |
| Probiotic alone | Active comparator | Dietary Supplement: Probiotic, Dietary Supplement: Zinc placebo, Biological: Rotavirus vaccine, Biological: Oral polio vaccineReceived daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine. |
| Placebo | Placebo comparator | Dietary Supplement: Probiotic placebo, Dietary Supplement: Zinc placebo, Biological: Rotavirus vaccine, Biological: Oral polio vaccineReceived daily zinc placebo and probiotic placebo, in addition to rotavirus vaccine and trivalent oral polio vaccine. |
Who may qualify
- Ages
- 5 to 16 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Infants 35-41 days old
- Live in area under surveillance
- Current weight ≥3.2 kg
- No syndromic evidence of immunocompromise as determined by medical doctor
- No prior illness requiring hospitalization
Key exclusion criteria (6 listed)
- Child has history of atopic symptoms
- Child has a known digestive system defect
- Child has history of chronic diarrhea
- Child has major congenital anomalies
- Child has received a prior dose of rotavirus vaccine
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 |
|---|---|---|
| ProbioticAlso: CulturelleA capsule that contains at least 1 x 10^9 Lactobacillus rhamnosus GG organisms per capsule. The contents of this capsule were given once daily orally. | Dietary supplement | Probiotic alone, Zinc and probiotic |
| ZincZinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally. | Dietary supplement | Zinc alone, Zinc and probiotic |
| Probiotic placeboThe probiotic placebo was manufactured by the same company that manufactured the probiotic and contained inulin powder but no Lactobacillus rhamnosus GG. The contents of the capsule were given once daily orally. | Dietary supplement | Placebo, Zinc alone |
| Zinc placeboThe zinc placebo excluded the zinc sulphate but contained lactose and was diluted to match the taste. 5 ml of this suspension was given orally once daily. | Dietary supplement | Placebo, Probiotic alone |
| Rotavirus vaccineAlso: Rotarix®1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks. | Biological | Placebo, Probiotic alone, Zinc alone, Zinc and probiotic |
| Oral polio vaccineAlso: Biopolio®A liquid trivalent polio vaccine provided orally at 6 and 10 weeks. | Biological | Placebo, Probiotic alone, Zinc alone, Zinc and probiotic |
Primary outcome
Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine
Time frame: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine
Defined as an increase in serum anti-rotavirus (RV) VP6 IgA antibodies consistent with seroconversion (detection of serum anti-RV VP6 immunoglobulin A (IgA) antibodies at a concentration ≥20 U/ml in a previously seronegative individual) or a fourfold rise in anti-RV VP6 IgA antibodies between baseline and 14 weeks of age. Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age).
Geometric Mean Concentration of Rotavirus-specific IgA
Time frame: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine
Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus was administered (14 weeks of age). Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age).
4 secondary outcomes
Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV)
Time frame: from first dose of OPV to 4 weeks after last dose of OPV
Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1
Time frame: 0, 4 and/or 7 day post dose 1 of rotavirus vaccine
Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2
Time frame: 0, 4 and/or 7 day post dose 2 of rotavirus vaccine
Serious Adverse Events (SAEs)
Time frame: from first day of study to 4 weeks after last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Gagandeep Kang, MD, PhD principal investigator
Christian Medical Center, Vellore, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Probiotic, Zinc and Rotavirus vaccine in people with Immunity to Oral Rotavirus Vaccine and Immunity to Oral Polio Vaccine, run by PATH at 1 site in India.
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 8 inclusion and 6 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 26 Dec 2018. 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 India. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine (time frame: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine). 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?
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 26 Dec 2018.