Effectiveness of Cranberry Ingestion on Bacterial Adhesion: An Adjunct Study
Condition: Asymptomatic Bacteriuria
MeSH terms: Bacteriuria
Study type: Interventional

Summary: 
      This study is to help determine if drinking cranberry juice can decrease risk for
      asymptomatic bacteriuria (ASB). ASB occurs when there are bacteria in the urine without any
      symptoms. It will also see if there is a difference in this effect between pregnant and
      non-pregnant women.This research project is also designed to see what happens to bacterial
      binding to the lining of the bladder after drinking cranberry juice when special problems
      occur with pregnancy such as diabetes (a sugar metabolism problem) or ASB is already
      occurring.
    

Detailed description: 
      This study is an adjunct to a proposal the premise of which is daily cranberry ingestion
      during pregnancy may be an effective preventative approach to development of asymptomatic
      bacteriuria (ASB), a condition which predisposes to both preterm birth and upper urinary
      tract infection. We proposed to NCCAM a pilot randomized, controlled trial (RCT) in which
      pregnant women beyond 12 weeks' gestational age will be assigned to one of three schedules
      for cranberry ingestion: Group A will consume cranberry juice twice a day with breakfast and
      dinner; Group B will consume cranberry juice at breakfast followed by placebo at dinner; and
      Group C will consume placebo with meals. Both the cranberry juice and placebo will be of
      scientific grade, provided by an NIH-contractor. Both are well-characterized, presenting a
      low-carbohydrate load and low-calorie content per dose (40 cal per 8 oz. dose). Our intent is
      to 1) generate data comparing the frequency of asymptomatic bacteriuria in pregnant women
      consuming cranberry juice daily versus placebo, and to 2) create the infrastructure to
      complete this pilot study and to gather sufficient data to support an R01 for a larger,
      multi-center RCT focused on the prevention of ASB in pregnancy with daily cranberry juice
      ingestion.

      The reviewers of our proposal enumerated specific weaknesses including 1) a need to evaluate
      urine from cranberry treated patients, and 2) consideration of bacterial virulence/adherence.
      The additional variable of gestational diabetes also received comment from the reviewers, and
      we acknowledge that predisposition in the Hispanic population to this obstetrical
      complication could impact results. A constituent of cranberries is fructose, which has been
      implicated in the inhibition of E. coli with type 1 fimbriae (mannose-sensitive) (2). We
      hypothesize that the glucosuria associated with diabetes in pregnancy may influence the
      effectiveness of cranberry to prevent asymptomatic bacteriuria.

      We must address these weaknesses to strengthen chances for continued funding and competitive
      renewal.

      We have made inquiries with other researchers, and have discovered no direct urine or serum
      assays by which to measure cranberry metabolites. We understand that there is an R21 proposal
      under consideration to develop a urinary assay for this purpose under the same RFA. Amy
      Howell, PhD, of the Marucci Center for Blueberry/Cranberry Research of Rutgers University,
      one of the field's foremost researchers in this field, and others have indirectly assayed
      compliance to cranberry by evaluating adherence of piliated E. coli strains before and after
      cranberry exposure (1). In response to the recent call for proposals for faculty research
      from the UCI Committee on Research, I proposed this pilot study in collaboration with Dr.
      Howell.

      In this proposal, we will collect the urine from various participants in the R21 trial so as
      to characterize the effect of cranberry juice ingestion on bacterial adherence. We will ask
      women to collect their urine for a four-hour time period including first-morning void. The
      urine samples will be sent to Dr. Howell's laboratory at Rutgers University for analysis. We
      will collect urine from pregnant women who are assigned to cranberry and to placebo, and from
      those women who develop bacteriuria following cranberry and following placebo ingestion. We
      also plan to identify a group of reproductive age, healthy, and non-pregnant women to ingest
      the active cranberry product or placebo for three days, and on the third day, collect a
      four-hour timed sample in the same manner as the pregnant women in our control group.
    

Intervention name(s): Cranberry Juice; De-Activated Cranberry juice
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Low-calorie, Low-carbohydrate content 8 oz dose of Cranberry juice; De-Activated Cranberry juice in the am, then placebo (P) in the pm
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Pregnancy; Cranberry; Asymptomatic Bacteruria