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

NCT01616693 | Completed Phase 4 Results DMC

• 1 other identifier: CMC ZP 2012; PATH HS-658
• Study Type: interventional
• Target: 620
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  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)

  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

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

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

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

• Serious Adverse Events (SAEs)

  from first day of study to 4 weeks after last dose

Study Arms (4)

Zinc and probiotic

EXPERIMENTAL

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

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.

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.

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.

Dietary Supplement: Probiotic placebo; Dietary Supplement: Zinc placebo; Biological: Rotavirus vaccine; Biological: Oral polio vaccine

Interventions

Probiotic DIETARY_SUPPLEMENT

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.

Also known as: Culturelle

Probiotic alone; Zinc and probiotic

Zinc DIETARY_SUPPLEMENT

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

Zinc alone; Zinc and probiotic

Probiotic placebo DIETARY_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.

Placebo; Zinc alone

Zinc placebo DIETARY_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.

Placebo; Probiotic alone

Rotavirus vaccine BIOLOGICAL

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

Also known as: Rotarix®

Placebo; Probiotic alone; Zinc alone; Zinc and probiotic

Oral polio vaccine BIOLOGICAL

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

Also known as: Biopolio®

Placebo; Probiotic alone; Zinc alone; Zinc and probiotic

Eligibility Criteria

• Age: 5 Weeks - 16 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• PATH: lead
• Christian Medical College, Vellore, India: collaborator
• Ministry of Science and Technology, India: collaborator

Study Sites (1)

Christian Medical Center, Vellore

Vellore, Tamil Nadu, 632 004, India

Location

MeSH Terms

Conditions

Poliomyelitis

Interventions

Probiotics; Zinc; Rotavirus Vaccines; RIX4414 vaccine; Poliovirus Vaccine, Oral

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Poliovirus Vaccines

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

(202) 822-0033

Study Officials

• Gagandeep Kang, MD, PhD

  Christian Medical Center, Vellore, India

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 12, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 26, 2018
• Results First Posted: November 30, 2018

Record last verified: 2018-12

Locations

IN (1)