HealthyPhase 1LAIVNCT01545349
Safety of Lactobacillus Rhamnosus GG Versus Placebo in Elderly Subjects Receiving Live Attenuated Influenza Vaccine
A Phase 1 study testing Lactobacillus rhamnosus GG ATCC 53103 (LGG) and Live attenuated influenza vaccine in people with Healthy and Influenza, run by Patricia L. Hibberd at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 to 80 yearsHealthy volunteers can take part
- What is being tested?
- Lactobacillus rhamnosus GG ATCC 53103 (LGG) and Live attenuated influenza vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 to 80 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
- Immune Globulin within the prior 6 months
- Immune modulating drugs such as Belimumab, azathioprine, mercaptopurine, methotrexate, hydroxychloroquine or leflunomide at any time or any oral or parenteral corticosteroid in the prior 12 months
- Fingolimod at any time
- Salicylates at doses higher than 163 mg/day for primary prevention of myocardial infarction. (Reye's Syndrome in adults is extremely rare - to our knowledge the oldest reported patient was aged 61 and as of 1989 when Reye Syndrome was more common, it had only been reported in 25 adults. In addition, increasing numbers of adults are being placed on low dose aspirin for primary and secondary prevention of cardiovascular disease, some of whom may also have influenza, but there has been no increase in reports or Reye's Syndrome in adults.)
- Presence of any of the following:
- Grade 2 or higher abnormal vital signs or abnormalities on physical exam during screening or presence of any wheezing on physical exam at baseline
- Indwelling catheter or implanted hardware/prosthetic device or feeding tube
- Current or within the last 2 years, any episode of bowel leak, acute abdomen, diverticulitis, colitis, bloody bowel movements or peptic ulcer disease, including any surgical procedure or current prescription medications for any of these conditions
- Current or within the last four weeks, active bowel disease such as an episode of infectious or non-infectious diarrhea, constipation or vomiting lasting more than 12 hours or current prescription medications for any of these conditions
- Any history of gastric or intestinal dysmotility, slowed transit time, variable small intestinal permeability, pancreatitis, history of gastrointestinal tract cancer or metastasis or inflammatory bowel disease or current prescription medication for any of these conditions
- Any history of Hepatitis B or Hepatitis C infections, cirrhosis, or chronic liver disease
- Underlying structural heart disease such as abnormal native heart valve or congenital abnormality, previous history of endocarditis or valve replacement, Stage IV congestive heart failure or chronic cardiovascular conditions (except hypertension)
- History of peripheral vascular disease or stroke
- Immunosuppression including HIV positive, solid organ or stem cell transplant recipient, receiving any oral or parenteral immunosuppressive therapy, neutrophil count < 500/mm3, or an anticipated drop in the neutrophil count to < 500/mm3 during the 56 days post LAIV vaccination or active or planned chemotherapy or radiotherapy
- History of collagen vascular or autoimmune disease
- History of renal disease
- History of chronic obstructive pulmonary disease or asthma
- History of neurologic or neuromuscular diseases
- History of hematologic diseases
- Diabetes or thyroid disease or metabolic disorder
- Active tuberculosis (TB), defined as undergoing a work up for suspected active TB infection or currently on treatment for active TB or scheduled for tuberculin test in the next 4 weeks
- Fever or acute illness or nasal congestion during the baseline visit (LAIV administration)
- Positive drug or alcohol testing at screening or positive breathalyzer at baseline or an unwillingness to undergo drug and alcohol testing
- Abnormal laboratory tests defined as any of the following:
- White blood cell (WBC)< 3.3 or > 12.0 K/microliters
- Neutrophil < 500/mm3
- Platelets < 125 K/microliter
- Hemoglobin males: < 12.0 g/dL; females: < 11.0 g/dL
- Creatinine > 1.8 mg/dL
- Blood urea nitrogen (BUN) > 27 mg/dL
- Aspartate aminotransferase (AST) > 1.25 ULN
- Alanine aminotransferase (ALT) > 1.25 ULN
- Alkaline phosphatase > 1.25 ULN
- Bilirubin (total) > 1.5 ULN
- Glucose (non-fasting) > 126 mg/dL
- Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody
- Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the subject participating in the study or would make it unlikely the subject could complete the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Double Blind Randomized Controlled Trial to Evaluate the Safety of Lactobacillus Rhamnosus GG ATCC 53103 (LGG) Versus Placebo in Elderly Subjects Receiving Live Attenuated Influenza Vaccine
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:
- LGG or placebo administered twice daily will be safe and well tolerated in elderly subjects who have just received the live attenuated influenza vaccine,
- The immune response to the influenza vaccine at day 21, 28, and 56 will be higher in the LGG group than the placebo group,
- 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.
- Being tested
- Lactobacillus rhamnosus GG ATCC 53103 (LGG), Placebo, Live attenuated influenza vaccine
- Keywords
- LGG, Immune response, Influenza vaccine, Elderly, Healthy, Microbiome
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus rhamnosus GG ATCC 53103 (LGG)Biological
Also called Culturelle
Study drug capsules (1x10^10 LGG/capsule) are to be taken orally twice a day every day on an outpatient basis for 28 days
PlaceboBiological
Placebo capsules composed of microcrystalline cellulose are to be taken orally twice a day on an outpatient basis for 28 days.
Live attenuated influenza vaccineBiological
Also called FluMist
0.2 mL pre-filled, single use intranasal spray
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Placebo; Biological: Live attenuated influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
HAI, MN titers and IgA titers will be measured at baseline and on days 21, 28, 56 post LAIV vaccination
Measured: Baseline through day 56 post LAIV vaccination
Anti influenza mucosal immune response (IgA titers)
IgA levels will be measured at baseline, and days 21, 28 and 56 post LAIV immunization
Measured: Baseline through day 56 post LAIV vaccination
Richness and microbial diversity in nasopharyngeal and stool specimens
Measure of the richness and microbial diversity in nasopharyngeal and stool specimens using pyrosequencing
Measured: Baseline through day 56 post LAIV vaccination
Anti influenza systemic immune response post TIV vaccination
Anti influenza systemic immune response (HAI and MN titers) will be measured before and 28 days after TIV immunization in the fall 2012.
Measured: Fall 2012 - prior to and 28 days post TIV vaccination
Occurence of influenza-like illness during 2012-2013 influenza season
Subjects will telephoned every month after receiving the TIV vaccination in the fall of 2012, through the end of the 2012-2013 influenza season, to determine if they have an influenza-like illness. They will also be asked to keep a study diary if they experience any influenza-like symptoms
Measured: Baseline through the end of the 2012-2013 influenza season (anticipated average of 13 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2012 (estimated)
- Study startFeb 2012
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patricia L. Hibberd
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Patricia L. Hibberd, Massachusetts General Hospital
- Investigators
- Patricia L Hibberd, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545349
- Sponsor's protocol ID
- 2011 P 002849
- Acronym
- LAIV
- Status last verified
- Jan 2017
- First submitted
- 29 Feb 2012
- Last updated
- 11 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Randomized Controlled Trial to Evaluate the Safety of Lactobacillus Rhamnosus GG ATCC 53103 (LGG) Versus Placebo in Elderly Subjects Receiving Live Attenuated Influenza Vaccine
- ClinicalTrials.gov ID
- NCT01545349
- Acronym / sponsor ID
- LAIV / 2011 P 002849
- Keywords
- LGG, Immune response, Influenza vaccine, Elderly, Healthy, Microbiome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Patricia L. HibberdUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 6 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- LGG or placebo administered twice daily will be safe and well tolerated in elderly subjects who have just received the live attenuated influenza vaccine,
- The immune response to the influenza vaccine at day 21, 28, and 56 will be higher in the LGG group than the placebo group,
- 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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LGG | Experimental | Biological: Lactobacillus rhamnosus GG ATCC 53103 (LGG), Biological: Live attenuated influenza vaccineLactobacillus 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. |
| Placebo | Placebo comparator | Biological: Placebo, Biological: Live attenuated influenza vaccinePlacebo capsules composed of microcrystalline cellulose are to be taken orally twice a day on an outpatient basis. |
Who may qualify
- Ages
- 65 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (52 listed)
- 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
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 |
|---|---|---|
| Lactobacillus rhamnosus GG ATCC 53103 (LGG)Also: CulturelleStudy drug capsules (1x10^10 LGG/capsule) are to be taken orally twice a day every day on an outpatient basis for 28 days | Biological | LGG |
| PlaceboPlacebo capsules composed of microcrystalline cellulose are to be taken orally twice a day on an outpatient basis for 28 days. | Biological | Placebo |
| Live attenuated influenza vaccineAlso: FluMist0.2 mL pre-filled, single use intranasal spray | Biological | LGG, Placebo |
Primary outcome
Occurrence of adverse events that are possibly or probably related to administration of LGG
Time frame: 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
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.
5 secondary outcomes
Anti-influenza systemic immune response (HAI, MN titers and IgA titers)
Time frame: Baseline through day 56 post LAIV vaccination
Anti influenza mucosal immune response (IgA titers)
Time frame: Baseline through day 56 post LAIV vaccination
Richness and microbial diversity in nasopharyngeal and stool specimens
Time frame: Baseline through day 56 post LAIV vaccination
Anti influenza systemic immune response post TIV vaccination
Time frame: Fall 2012 - prior to and 28 days post TIV vaccination
Occurence of influenza-like illness during 2012-2013 influenza season
Time frame: Baseline through the end of the 2012-2013 influenza season (anticipated average of 13 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
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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.
Patricia L Hibberd, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lactobacillus rhamnosus GG ATCC 53103 (LGG) and Live attenuated influenza vaccine in people with Healthy and Influenza, run by Patricia L. Hibberd at 1 site in United States.
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 13 inclusion and 52 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 11 Jan 2017. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Occurrence of adverse events that are possibly or probably related to administration of LGG (time frame: 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). 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 11 Jan 2017.