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

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ClinicalTrials.gov Identifier: NCT01616693
Recruitment Status : Completed
First Posted : June 12, 2012
Results First Posted : November 30, 2018
Last Update Posted : November 30, 2018
Sponsor:
Collaborators:
Christian Medical College, Vellore, India
Ministry of Science and Technology, India
Information provided by (Responsible Party):
PATH

June 6, 2012
June 12, 2012
April 23, 2018
November 30, 2018
November 30, 2018
July 2012
July 2013   (Final data collection date for 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 ]
    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).
Change in Rotavirus IgA immune response [ Time Frame: Baseline and 4 weeks post rotavirus vaccine dose 2 ]
A serologic immune response to rotavirus vaccine will be defined as an increase in serum anti-rotavirus (RV) VP6 IgA antibodies consistent with seroconversion (detection of serum anti-RV VP6 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.
Complete list of historical versions of study NCT01616693 on ClinicalTrials.gov Archive Site
  • 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 ]
    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 [ Time Frame: 0, 4 and/or 7 day post dose 1 of rotavirus vaccine ]
    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 [ Time Frame: 0, 4 and/or 7 day post dose 2 of rotavirus vaccine ]
    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) [ Time Frame: from first day of study to 4 weeks after last dose ]
    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.
  • Change in Polio neutralizing antibody titer immune response [ Time Frame: Baseline and 4 weeks post OPV dose 2 ]
    A serologic immune response to oral polio vaccine will be 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 because it is conservative in that it gives the lowest immune response of all three polio antigens.
  • Change in Rotavirus IgA immune response (GMTs) [ Time Frame: Baseline and 4 weeks post rotavirus vaccine dose 2 ]
    Geometric mean titers (GMTs) of serum anti-rotavirus VP6 IgA antibody
  • Serious adverse events (SAEs) [ Time Frame: Day 0, vaccine dose 1 to 4 weeks post vaccine dose 2 ]
    Serious adverse events (SAEs) and solicited adverse events (AEs) will be monitored.
  • Rotavirus vaccine shedding [ Time Frame: 0, 4 and/or 7 day post dose 1 and dose 2 rotavirus vaccine ]
    Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by RT-PCR.
Not Provided
Not Provided
 
Zinc and/or Probiotic Supplementation of Rotavirus and Oral Polio Virus Vaccines
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.

Co- Primary objectives:

  1. 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.
  2. 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.
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
  • Immunity to Oral Rotavirus Vaccine
  • Immunity to Oral Polio Vaccine
  • Shedding of Oral Rotavirus Vaccine
  • Dietary Supplement: Probiotic
    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.
    Other Name: Culturelle
  • Dietary Supplement: Zinc
    Zinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally.
  • Dietary Supplement: Probiotic placebo
    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.
  • Dietary Supplement: Zinc placebo
    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.
  • Biological: Rotavirus vaccine
    1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
    Other Name: Rotarix®
  • Biological: Oral polio vaccine
    A liquid trivalent polio vaccine provided orally at 6 and 10 weeks.
    Other Name: Biopolio®
  • Experimental: Zinc and probiotic
    Received daily zinc and probiotic supplements, in addition to rotavirus vaccine and trivalent oral polio vaccines.
    Interventions:
    • Dietary Supplement: Probiotic
    • Dietary Supplement: Zinc
    • Biological: Rotavirus vaccine
    • Biological: Oral polio vaccine
  • Active Comparator: Zinc alone
    Received daily zinc and probiotic placebo supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.
    Interventions:
    • Dietary Supplement: Zinc
    • Dietary Supplement: Probiotic placebo
    • Biological: Rotavirus vaccine
    • Biological: Oral polio vaccine
  • Active Comparator: Probiotic alone
    Received daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.
    Interventions:
    • Dietary Supplement: Probiotic
    • Dietary Supplement: Zinc placebo
    • Biological: Rotavirus vaccine
    • Biological: Oral polio vaccine
  • Placebo Comparator: Placebo
    Received daily zinc placebo and probiotic placebo, in addition to rotavirus vaccine and trivalent oral polio vaccine.
    Interventions:
    • Dietary Supplement: Probiotic placebo
    • Dietary Supplement: Zinc placebo
    • Biological: Rotavirus vaccine
    • Biological: Oral polio vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
620
560
July 2013
July 2013   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
5 Weeks to 16 Weeks   (Child)
Yes
Contact information is only displayed when the study is recruiting subjects
India
 
 
NCT01616693
CMC ZP 2012; PATH HS-658
Yes
Not Provided
Not Provided
PATH
PATH
  • Christian Medical College, Vellore, India
  • Ministry of Science and Technology, India
Principal Investigator: Gagandeep Kang, MD, PhD Christian Medical Center, Vellore, India
PATH
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP