Cranberry and Quillaja on Symptoms of Uncomplicated UTI

Study Overview
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Brief Summary
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This study will investigate the effects of cranberry and quillaja capsules on symptoms of uncomplicated urinary tract infections.

Detailed Description
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Urinary tract infection (UTI) is one of the most common bacterial infections in humans and it disproportionately affects women. Currently there are only a few alternatives to antibiotics for treatment of UTI. Although symptomatic relief occurs more quickly in women treated with oral antibiotics for uncomplicated UTIs, patients appear to successfully resolve their UTI without antibiotic therapy. While antibiotics are the mainstay of therapy, there are growing concerns about collateral effects impacting healthy microbiomes and anti-bacterial resistance patterns. Recent estimates from the CDC indicate that more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35,000 people die as a result. The proposed research fills a key knowledge gap that will be critical in determining the role of a non-antibiotic substance with the potential to treat UTIs by modulating the urinary and gut microbiome to restore health and minimize the reliance on traditional antibiotic therapy while also preventing antibiotic resistance. In addition, this study will provide early evidence of the short-term symptom and urinary and gut microbiome changes following ingestion of two botanical food substances (cranberry and quillaja) that have the potential for beneficial effects on the microbiome and UTI symptoms.

Official Title
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A Proof-of-concept, Feasibility Study to Investigate the Effect of Cranberry and Quillaia Extract Type II on Symptoms in Women With Uncomplicated Urinary Tract Infection and to Study the Modulation of the Urinary and Gut Microbiome Pre- and Post-antibiotic Use

Conditions
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UTI, Urinary Tract Infections, UTI - Lower Urinary Tract Infection

Intervention / Treatment
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* Other: Pacran and Sapnov P quillaja


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal women 18 years and over Presenting with typical symptoms of an uncomplicated UTI Positive leukocyte or nitrite on in-office urine dipstick confirmed Able to swallow capsules Willing and able to fill out/ answer questionnaires and comply with the study requirement Willing to initiate clinically prescribed antibiotic therapy (typically 5-day antibiotic). Provided written informed consent BMI >17.5kg m2 and <35kg m2 Exclusion Criteria: Regular use of Vaccinium containing products (e.g. all forms of blueberries, cranberries, bilberry, lingonberry etc. i.e. fruit, dried fruit, pills, juices or supplements) within 28 days of Day 1, Allergy to cranberry, tree bark, or quillaja. Use of any antibacterial supplements or products, that in the opinion of the Medical Investigator may interfere with the study outcomes, within 28 days of Day 1 A history of >5 UTIs in the last 6 months (confirmed by self-report or health professional) Use of antibiotics or antibiotics for prophylaxis to treat a UTI within 28 days of Day 1 Women of child bearing potential not willing to use adequate and effective methods of contraception throughout the study, in the opinion of the Investigator Positive urine dipstick pregnancy test at screening on Day 1, currently pregnant and/or breastfeeding History of an adverse reaction or known hypersensitivity or suspected allergy to the investigational product ingredients History of pyelonephritis or reflux Presence of an intermittent or indwelling urinary catheter Anatomical abnormalities of the urinary tract (self-reported) History of or known clinically significant renal or urological disease (self-reported), at the discretion of the investigator History of or known clinically significant cardiac disease, at the discretion of the investigator History of or known clinically significant liver disease, at the discretion of the investigator History of or known clinically significant gastrointestinal disease, at the discretion of the investigator History of or known metabolic disorder or diabetes History of or known incomplete emptying of bladder History or presence of alcohol or illicit drug abuse, any surgical history, clinical condition or organ dysfunction that in the opinion of the Medical Investigator may affect the participant's ability to participate in the study or the study results Currently hospitalized or any planned hospitalizations within the study period. Immunocompromised participants or participants receiving immunosuppressive medication Currently taking warfarin or has received Warfarin within 28 days of Day 1 Received an investigational drug within 28 days of Day 1 (pills, juices or supplements)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, single site, single group prospective cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cranberry and Quillaja<br>one 450mg cranberry capsule and one 50mg quillaja capsule in the morning and evening for 14 days. | Other: Pacran and Sapnov P quillaja<br>* Cranberry (450 mg) and quillaja (50 mg) capsules taken orally twice daily (morning and evening) for a total daily dose of 900 mg cranberry and 100 mg quillaja for 14 days. Nitrofurantoin 100 mg taken orally twice daily for five days as a rescue medication if symptoms do not subside.<br>* Other names: Quillaia extract type II;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Tract Infection Symptoms Assessment Questionnaire (UTISA) | This questionnaire assesses the degree of symptoms and bother on a scale of 0 to 3, and has 3 domains of urinary regularity, problems with urination and pain associated with urination. The fourth domain includes the presence of hematuria. Subjects will complete the UTISA questionnaire every day for 14 days. | 14 days | 
| Time to UTI antibiotic initiation | This will be assessed using study form, UTI Comfort Measure Assessment. Subjects will have access to a clinically prescribed UTI antibiotic, nitrofurantoin 100mg. Subjects will be asked to record each day their intake of any antibiotic during the study period. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome changes prior to and post antibiotic initiation | This outcome measure can only be assessed for those participants that require antibiotic initiation. Changes in the entire bacterial community prior to and post antibiotic use will be assessed in the lab from faecal and urine samples collected by the participant. The microbes may vary by participant and the study will be looking at which ones present themselves in each case. Units of measure via culture are colony forming units per g (cfu/g). | 14 days |