Safety of Synbiotics as Adjuvant to Influenza Vaccine in Elderly

Study Overview
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Brief Summary
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Probiotics are viable commensal microorganisms that promote the establishment of beneficial microflora. Animal and human studies demonstrate that probiotics can enhance body's immune response to stimuli. Mayo Clinic in conjunction with Agri-King Corporation has developed a novel synbiotic called AKSB (Agri-King Synbiotic) that contains a probiotic bacterium (Enterococcus faecium, microencapsulated SF68 or Ventrux ME 30), a probiotic yeast (Saccharomyces cerevisiae, Lynside® Pro-Lay 1), and a prebiotic (fructo-oligosaccharide [FOS], NutraFlora®). This phase I placebo-controlled trial of AKSB in normal human volunteers, over 65 years of age, is designed to study the safety of this probiotic when patients are also receiving an influenza vaccine. If this study shows that AKSB is safe then our aim is to do a larger study to see if we can improve influenza vaccine immune response while taking the probiotic compared to placebo.

Official Title
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A Phase I Trial of the Safety and Efficacy of Adjuvant AKSB (Agri-King Synbiotic) Synbiotic in Patients 65 Years of Age and Older Receiving the Influenza Vaccine

Conditions
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Influenza

Intervention / Treatment
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* Biological: Synbiotic AKSB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persons, male and female, 65 years of age and older. Eligible and willing to receive the influenza vaccine and take the study drug. Not currently on immunosuppressive drugs such as chemotherapy, oral or parenteral prednisone or Tumor Necrosis Factor-alpha (TNF-α) inhibitor therapy. Not allergic to chicken/egg protein. Willing to have blood drawn (4 times) during the study. Willing to complete a simple diary documenting toxicity, pill count and any side effects of the medication and any reported illnesses during this period. Willingness to take 4 capsules per day, keep a symptom and capsule diary, and return these materials to the clinic at the conclusion of the study. Willingness to avoid all over the counter nutritional supplements, probiotics, and yogurts containing probiotics during the duration of the study. Patients who have provided their written informed consent prior to participation in the study and have signed and dated an appropriate Health Insurance Portability and Accountability Act (HIPAA) authorization form. Blood laboratory results within the 7 days of starting study drug Normal liver function as shown by: serum AST within upper limits of normal Adequate renal function as shown by : serum creatinine ≤ 2.0 mg/dL Hemoglobin > 11gm/dL; WBC: > 3.5X109 /L and platelets > 100 X 109 /L Exclusion Criteria: Antibiotic use - current or within 2 weeks prior to start of the study. Chicken/Egg hypersensitivity or hypersensitivity to influenza vaccine components such as bactopeptone, beta-propiolactone, neomycin, gentamicin, monosodium glutamate, formaldehyde or formalin, gelatin, polyethylene glycol p-iso-octylphenyl ether (Triton X-100), polymyxin B, polyoxyethylene 9-10 nonyl phenol (Triton N-101, octoxynol 9), or thimerosal. Talc allergy Influenza vaccine within the prior 12 months. Immunosuppressed status either from illness such as acquired immunodeficiency syndrome (AIDS), or with concomitant chemotherapy, or iatrogenic immunosuppression such as prednisone or other drugs such as TNF-α inhibitor therapy. History of known serious illness such as active cancer (except localized skin or non-metastatic prostate cancer), poorly controlled congestive heart failure, poorly controlled diabetes, acute or progressive renal or hepatic failure, chronic obstructive lung disease requiring oxygen. Ongoing anti-influenza therapy with amantadine, rimantadine, oseltamivir or zanamivir Active or recent (within last 6 months) history consistent with acute influenza illness. Febrile illness with headache, sore throat and temperature more than 37.5C on the day of enrollment. Known chronic inflammatory bowel disease such as Crohn's disease, active bowel cancer (defined as being on chemotherapy or having an untreated bowel cancer) Hypersensitivity to any components of the AKSB, placebo or the vaccine. Oral typhoid vaccine use in the last 2 weeks. Patients who have participated in a clinical study and/or received any investigational medication during the last month (30 days) preceding study Day 1; or currently enrolled in an investigational study. Patients who, in the opinion of the investigator, possess insufficient mental or reading ability that prevents their understanding and providing informed consent and appropriate HIPAA authorization; Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol; Patients who are unwilling or unable to comply with the study protocol for any other reason. History of Guillain-Barré Syndrome within 6 weeks following a previous dose of the inactivated vaccine. Allergy or contraindication to two or more of the following: vancomycin, penicillins, daptomycin, linezolid Allergy or contraindication to two or more of the following: fluconazole, deoxycholate amphotericin B, liposomal amphotericin B, itraconazole or voriconazole Blood laboratory results within the 7 days of starting study drug Abnormal normal liver function as shown by: serum AST above the upper limits of normal Impaired renal function as shown by : i. serum creatinine > 2.1 mg/dL Hemoglobin < 11gm/dL; WBC: < 3.5X109 /L and platelets < 100 X 109 /L

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Synbiotic AKSB<br>Participants (healthy > 65 year old persons) will be randomized to take the synbiotic AKSB. All participants will also receive inactivated trivalent Influenza vaccine while being on the AKSB. We will assess safety of the AKSB in this setting. We will also assess the stool microbiology in relation to vancomycin-resistant enterococcus and probiotic strain enterococcus. We will also assess influenza vaccine response in patients on AKSB | Biological: Synbiotic AKSB<br>* AKSB is a novel synbiotic that contains a probiotic bacterium (Enterococcus faecium, microencapsulated SF68 or Ventrux ME 30), a probiotic yeast (Saccharomyces cerevisiae, Lynside® Pro-Lay 1), and a prebiotic (fructo-oligosaccharide [FOS], NutraFlora®).<br>|
| Placebo Comparator: Talc Placebo<br>Participants (healthy > 65 year old persons) will be randomized to take the placebo. All participants will also receive inactivated trivalent Influenza vaccine while being on the placebo. We will also assess the stool microbiology in relation to vancomycin-resistant enterococcus. We will also assess influenza vaccine response in patients on placebo. | Biological: Synbiotic AKSB<br>* AKSB is a novel synbiotic that contains a probiotic bacterium (Enterococcus faecium, microencapsulated SF68 or Ventrux ME 30), a probiotic yeast (Saccharomyces cerevisiae, Lynside® Pro-Lay 1), and a prebiotic (fructo-oligosaccharide [FOS], NutraFlora®).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with adverse events | To evaluate the safety and tolerability of AKSB when administered with the influenza vaccine as compared to the influenza vaccine alone with placebo in patients ≥65 years of age. | 127 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare stool presence of probiotic enterococcal strain | To evaluate for stool VRE presence pre-post intervention and to compare molecular fingerprinting of VRE isolated with the SF68 strain of enterococci used in the study drug to demonstrate safety of the study drug. | baseline to 21 days | 
| Immune response to Influenza A vaccine in the AKSB arm compare to Placebo | To determine whether AKSB can increase the protection rate [PR, (number of participants that achieve the protective antibody titer)] by 20% in the AKSB arm at days 14, 28 days and 120 days after vaccination among the elderly patients (≥ 65 years of age). Effect of age (65-75 years and >75 years), gender, underlying medical history and previous vaccination status (within the last 2 years) will evaluated. | days 14, 28 days and 120 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, AKSB, probiotic, synbiotic, enterococcus, Saccharomyces, elderly, influenza, vaccine, immune, response