Probiotic Ingestion and Isoagglutinin Titers
Condition: Isoagglutinin-Mediated Hemolysis; Probiotic Toxicity
MeSH terms: Hemolysis
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Probiotics are oral food supplements containing live bacteria that may be beneficial to
           a person s digestion or general health. Probiotics are available as tablets, powder, or
           liquid supplements and are frequently used to supplement yogurt. They are available for
           purchase without prescription in most supermarkets.

        -  The bacteria in probiotic supplements commonly express sugar substances on their
           surface. These sugar substances are similar to group A and B blood group sugars, called
           antigens. These antigens determine a person s blood group. Researchers are studying the
           effect of probiotic supplements on the amount of blood group antibodies that are present
           in a person s blood.

      Objectives:

        -  To determine whether taking oral probiotic supplements increases anti-A and anti-B
           isoagglutinins (antibodies that cause red blood cells to clump together) in healthy
           subjects.

        -  To study the frequency of these effects and determine whether there is a dose-response
           relationship with probiotics and isoagglutinin titers.

      Eligibility:

        -  Healthy adults, 18 years or older, with type A, B, or O blood.

        -  Female participants need to have undergone menopause or have had a hysterectomy.

        -  Individuals are ineligible if they currently donate platelets; have a history of
           ulcerative colitis or Crohn s disease; have had major bowel surgery; are pregnant or
           capable of becoming pregnant; have a bleeding or clotting disorder; have a history of a
           blood disorder or immune deficiency; have a history of high-risk behaviors for exposure
           to HIV or hepatitis B or C; have diabetes; have received vaccinations in the past 2
           months, with the exception of the flu vaccine; are currently taking immunosuppressive
           medications; are currently taking antibiotics; or have taken probiotic supplements
           within the last 12 months.

      Design:

        -  Researchers will conduct the following tests throughout the 28-week study:

             -  Blood samples will be drawn every 2 weeks to measure the quantity of isoagglutinin
                titers.

             -  Depending on individual results, continued blood testing may be done every 3 months
                for 1 year, then every 6 to 12 months for up to 5 years.

        -  Study subjects will take a probiotic supplement at a dose of 1 to 3 caplets per day for
           18 consecutive weeks according to the following schedule:

             -  During the first 6-week period, the subject will take one probiotic tablet daily.

             -  During the second 6-week period, the subject will take one probiotic tablet twice
                daily.

             -  During the third 6-week period, the subject will take one probiotic tablet three
                times daily.

        -  Control group subjects will be followed in a similar manner but will not take probiotic
           supplements.

        -  The outcome measure is the percent of probiotic ingestors (the study subjects) versus
           control group subjects who experience a fourfold or greater rise in isoagglutinin titer.

        -  Study subjects will receive the following financial compensation: $10 per blood sample,
           for a maximum of $240 if all 24 samples are collected; $100 after completing the first
           6-week period; $150 after completing the second 6-week period; and $200 after completing
           the third 6-week period.

        -  Control subjects will receive $10 per blood sample, for a maximum of $150 if all 15
           samples are collected.
    

Detailed description: 
      Probiotics are over-the-counter dietary supplements which contain live bacteria. These
      bacteria are normally present in the gastrointestinal tract and may provide health benefits
      when added to a regular diet. Common reasons for taking probiotic supplements include
      repopulating the gut with lactobacilli after taking antibiotics and aiding in the treatment
      of inflammatory bowel disease, lactose intolerance, and gastrointestinal infections.

      The gut of neonates is sterile and becomes colonized with bacteria during the first few
      months of life. Many of these bacteria possess terminal sugar structures on their membrane
      components that are chemically similar to A and B blood group substances present on red
      cells. Antibodies to A and B blood group substances are not present at birth. Early in life,
      infants lacking A or B antigens on their red cells recognize the corresponding antigens on
      bacteria and form antibodies against bacterial sugars that cross react with the corresponding
      red cell antigen. These antibodies are known as anti-A and anti-B isoagglutinins. They do not
      cause disease, but are important in the transfusion of compatible blood units.

      Prior studies have suggested that probiotics consumed in large doses may provoke the
      formation of high titer isoagglutinins. This has relevance for transfusion of platelet
      components, in that, since ABO-matching of platelets is not necessary, minor
      ABO-incompatibility between donor and recipient is present in 10-20% of plateletpheresis
      components transfused nationwide. Plateletpheresis components derived from donors taking
      probiotics might contain high titer isoagglutinins, which could cause hemolytic reactions in
      group A and B recipients.

      The objectives of this study are (1) to determine whether taking oral probiotic supplements
      increases anti-A and anti-B isoagglutinins in healthy subjects, (2) to study the frequency of
      these effects and determine whether there is a dose-response relationship with probiotics and
      isoagglutinin titers.

      Study subjects will be asked to take a probiotic supplement at a dose of 1-3 caplets per day
      for 18 weeks. Blood samples will be drawn every 2 weeks during that time. Depending on
      individual results, continued blood testing may be done every 3 months for a year, then every
      6-12 months for up to 5 years. A group of control subjects will be followed in a similar
      manner, but will not take probiotic supplements. The outcome measure is the percent of
      probiotic ingestors versus controls who experience a four-fold or greater rise in
      isoagglutinin titer in association with a final titer of at least 128.
    

Intervention name(s): Probiotic Supplement
Intervention type(s): Dietary Supplement
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Probiotics; Isoagglutinins; Anti-A; Anti-B; Hemolysis; Healthy Volunteer; HV