Safety of Lactobacillus Rhamnosus GG Versus Placebo in Elderly Subjects Receiving Live Attenuated Influenza Vaccine

NCT01545349 | Completed Phase 1 DMC

• 1 other identifier: 2011 P 002849
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, randomized controlled trial to evaluate the safety of Lactobacillus rhamnosus GG (LGG) versus placebo in elderly subjects receiving the live attenuated influenza vaccine. Lactobacilli are part of the normal flora of the intestine. LGG is one of several strains of Lactobacilli that is used as a probiotic or microorganism administered to confer "health benefits". Our research is focused on studying the possible therapeutic effects of LGG. The study hypotheses are:

1. 1.LGG or placebo administered twice daily will be safe and well tolerated in elderly subjects who have just received the live attenuated influenza vaccine,
2. 2.The immune response to the influenza vaccine at day 21, 28, and 56 will be higher in the LGG group than the placebo group,
3. 3.The diversity of the microbiota in nasopharyngeal and stool specimens at day 21, 28, and 56 will be greater in the LGG group than the placebo group.

Conditions

Healthy; Influenza

Keywords

LGG; Immune response; Influenza vaccine; Elderly; Healthy; Microbiome

Outcome Measures

Primary Outcomes (1)

• Occurrence of adverse events that are possibly or probably related to administration of LGG

  Adverse events will be detected during study visits with standardized questionnaires, medical history, vital signs, physical examinations, laboratory tests and review of subject diaries as well as between study visits on telephone calls based on responses to adverse event questionnaires. Additionally, subjects are encouraged to call the PI or study staff at any time if they are experiencing an adverse event.

  Subjects will be followed from the study start through the end of the 2012-2013 influenza season (as defined by CDC) with an anticipated average for most subjects of 13 months

Secondary Outcomes (5)

• Anti-influenza systemic immune response (HAI, MN titers and IgA titers)

  Baseline through day 56 post LAIV vaccination

• Anti influenza mucosal immune response (IgA titers)

  Baseline through day 56 post LAIV vaccination

• Richness and microbial diversity in nasopharyngeal and stool specimens

  Baseline through day 56 post LAIV vaccination

• Anti influenza systemic immune response post TIV vaccination

  Fall 2012 - prior to and 28 days post TIV vaccination

• Occurence of influenza-like illness during 2012-2013 influenza season

  Baseline through the end of the 2012-2013 influenza season (anticipated average of 13 months)

Study Arms (2)

LGG

EXPERIMENTAL

Lactobacillus rhamnosus GG (LGG) containing 1x10\^10 LGG per capsule will be given to subjects with verbal and written instructions at the baseline visit. Capsules are to be taken orally twice a day on an outpatient basis.

Biological: Lactobacillus rhamnosus GG ATCC 53103 (LGG); Biological: Live attenuated influenza vaccine

Placebo

PLACEBO COMPARATOR

Placebo capsules composed of microcrystalline cellulose are to be taken orally twice a day on an outpatient basis.

Biological: Placebo; Biological: Live attenuated influenza vaccine

Interventions

Lactobacillus rhamnosus GG ATCC 53103 (LGG) BIOLOGICAL

Study drug capsules (1x10\^10 LGG/capsule) are to be taken orally twice a day every day on an outpatient basis for 28 days

Also known as: Culturelle

LGG

Placebo BIOLOGICAL

Placebo capsules composed of microcrystalline cellulose are to be taken orally twice a day on an outpatient basis for 28 days.

Placebo

Live attenuated influenza vaccine BIOLOGICAL

0.2 mL pre-filled, single use intranasal spray

Also known as: FluMist

LGG; Placebo

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65-80 years
• Willing to complete the informed consent process
• Able and willing to participate for the planned duration of the study, including availability for follow-up telephone contact
• Is community dwelling for the past two years
• Has received routine physical in the past two years
• Has no new chronic conditions in the past two years
• Identifies a primary care clinician
• Has received recommended preventive services (Task Force for Clinical Preventive Services) for vaccination and cancer prevention/detection, e.g.:
• Pneumococcal vaccination
• Mammography
• Screening colonoscopy for colon cancer
• Willing to comply with protocol and report on compliance and side effects during the study period
• Informed consent obtained and signed prior to screening

You may not qualify if:

• Vaccination with any vaccine within the one month period prior to study enrollment or intent to receive any other vaccine during the study period, other than TIV in fall 2012
• History of hypersensitivity to any influenza vaccine components including eggs, egg proteins, gentamicin, gelatin or arginine
• History of avoidance of egg and/or egg-based products for any reason, unless they have previously received TIV or LAIV without hypersensitivity
• History of Guillain-Barre syndrome
• Acute febrile illness within the week prior to LAIV immunization - immunization deferred until illness resolved
• Consumption of supplements or food products containing LGG or probiotics for 28 days prior to the start of the study or consumption of yogurt that has the "live and active" cultures seal
• Known or suspected allergies to probiotics, Lactobacillus, microcrystalline cellulose, gelatin or antibiotics that may be used to treat LGG bacteremia or infection (i.e., subject able to tolerate at least 2 of the following regimens - Ampicillin or other beta lactam antibiotic, and Clindamycin, and Moxifloxacin)
• Received oral or parenteral antibiotics within 4 weeks of enrollment or prescribed antibiotics on the day or enrollment
• Drug or alcohol abuse, defined as the continued use of alcohol despite the development of social, legal, or health problems, within the previous 12 months
• Hospitalization, major surgery or endoscopy within the last 3 months
• Scheduled hospital admission or surgery within 3 months of enrollment
• Resident of a nursing home or rehabilitation center
• Close and/or household contact with severely immunocompromised persons (e.g., transplant recipients, cancer patients)
• Receipt of any of the following medications within the specified time frame:
• Antiviral agents for influenza A and B in the prior 2 weeks (anti-influenza medications are unlikely to be needed after LAIV immunization since LAIV will be administered at the end of the influenza season, but should be prescribed if clinically indicated)

Sponsors & Collaborators

• Patricia L. Hibberd: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; FluMist

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Patricia L Hibberd, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Global Health; Department of Pediatrics

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 6, 2012
• Study Start: February 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 11, 2017

Record last verified: 2017-01

Locations

US (1)