Zinc and/or Probiotic Supplementation of Rotavirus and Oral Polio Virus Vaccines

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

India

Study Type

Interventional

Intervention

Probiotic

Zinc

Probiotic placebo

Zinc placebo

Rotavirus vaccine

Oral polio vaccine

About this trial

This is an interventional basic science trial for Immunity to Oral Rotavirus Vaccine focused on measuring rotavirus, polio, zinc supplement, probiotic supplement, rotavirus vaccine shedding

Eligibility Criteria

5 Weeks - 16 Weeks (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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)

Sites / Locations

Christian Medical Center, Vellore

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Zinc and probiotic

Zinc alone

Probiotic alone

Placebo

Arm Description

Received daily zinc and probiotic supplements, in addition to rotavirus vaccine and trivalent oral polio vaccines.

Received daily zinc and probiotic placebo supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.

Received daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.

Received daily zinc placebo and probiotic placebo, in addition to rotavirus vaccine and trivalent oral polio vaccine.

Outcomes

Primary Outcome Measures

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).

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).

Secondary Outcome Measures

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).

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.

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.

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.

Full Information

NCT ID

NCT01616693

First Posted

June 6, 2012

Last Updated

December 3, 2018

Sponsor

PATH

Collaborators

Christian Medical College, Vellore, India, Ministry of Science and Technology, India

1. Study Identification

Unique Protocol Identification Number

NCT01616693

Brief Title

Zinc and/or Probiotic Supplementation of Rotavirus and Oral Polio Virus Vaccines

Official Title

Supplementation With Zinc and/or Probiotics to Enhance the Immune Response of Oral Rotavirus and Polio Vaccines in Indian Infants

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

July 2012 (undefined)

Primary Completion Date

July 2013 (Actual)

Study Completion Date

July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PATH

Collaborators

Christian Medical College, Vellore, India, Ministry of Science and Technology, India

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

620 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Zinc and probiotic

Arm Type

Experimental

Arm Description

Received daily zinc and probiotic supplements, in addition to rotavirus vaccine and trivalent oral polio vaccines.

Arm Title

Zinc alone

Arm Type

Active Comparator

Arm Description

Received daily zinc and probiotic placebo supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.

Arm Title

Probiotic alone

Arm Type

Active Comparator

Arm Description

Received daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Received daily zinc placebo and probiotic placebo, in addition to rotavirus vaccine and trivalent oral polio vaccine.

Intervention Type

Dietary Supplement

Intervention Name(s)

Probiotic

Other Intervention Name(s)

Culturelle

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Zinc

Intervention Description

Zinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally.

Intervention Type

Dietary Supplement

Intervention Name(s)

Probiotic placebo

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Zinc placebo

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Rotavirus vaccine

Other Intervention Name(s)

Rotarix®

Intervention Description

1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.

Intervention Type

Biological

Intervention Name(s)

Oral polio vaccine

Other Intervention Name(s)

Biopolio®

Intervention Description

A liquid trivalent polio vaccine provided orally at 6 and 10 weeks.

Primary Outcome Measure Information:

Title

Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine

Description

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).

Time Frame

from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine

Title

Geometric Mean Concentration of Rotavirus-specific IgA

Description

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).

Time Frame

from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine

Secondary Outcome Measure Information:

Title

Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV)

Description

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).

Time Frame

from first dose of OPV to 4 weeks after last dose of OPV

Title

Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1

Description

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.

Time Frame

0, 4 and/or 7 day post dose 1 of rotavirus vaccine

Title

Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2

Description

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.

Time Frame

0, 4 and/or 7 day post dose 2 of rotavirus vaccine

Title

Serious Adverse Events (SAEs)

Description

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.

Time Frame

from first day of study to 4 weeks after last dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Weeks

Maximum Age & Unit of Time

16 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gagandeep Kang, MD, PhD

Organizational Affiliation

Christian Medical Center, Vellore, India

Official's Role

Principal Investigator

Facility Information:

Facility Name

Christian Medical Center, Vellore

City

Vellore

State/Province

Tamil Nadu

ZIP/Postal Code

632 004

Country

India

Immunity to Oral Rotavirus Vaccine, Immunity to Oral Polio Vaccine, Shedding of Oral Rotavirus Vaccine

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial