Isoagglutinin-Mediated HemolysisPhase 1NCT00891787
Probiotic Ingestion and Isoagglutinin Titers
A Phase 1 study testing Probiotic Supplement in people with Isoagglutinin-Mediated Hemolysis and Probiotic Toxicity, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Isoagglutinin-Mediated Hemolysis, Probiotic Toxicity
- What is being tested?
- Probiotic Supplement
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Apr 2009to 6 Apr 2011
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be healthy
- Subjects must be greater than or equal to 18 and less than or equal to 70 years of age
- Subjects must have an ABC blood group of A, B or O
- Laboratory values within established guidelines for participation in clinical studies:
- AST/ALT less than or equal to 2 times ULN; creatinine less than or equal to ULN; hemoglobin greater than or equal to 12.5 g/dL (males and females)
- Subjects must be willing to sign consent to participate in the protocol
Who cannot join
- ABO blood group of AB
- Current apheresis platelet donor in the NIH DTM
- Current or past history of gastrointestinal disease or surgery including: Crohn s disease, ulcerative colitis, celiac disease, irritable bowel syndrome, gastric bypass or banding, esophagectomy, gastrectomy, small bowel resection, colectomy, and any history of gastrointestinal malignancy including pancreatic carcinoma
- Vaccination within the last 2 months, with the exception of the influenza vaccine
- A history of high risk behaviors for exposure to HIV, HBV, HCV, HTLV (no intravenous drug use in past 5 years, no male sex with males in last 5 years)
- Confirmed positive test result for anti-HIV-1/2, anti-HCV, anti-HTLV I/Il, anti-T.pallidum, or H BsAg.
Show all 13Show fewer
- History of bleeding or clotting disorders
- History of hematologic malignancy
- History of inherited or acquired immune deficiency
- Diabetes mellitus (type I or II)
- Women of child-bearing potential
- Subjects currently taking immunosuppressive medications
- Subjects who have taken probiotic supplements within the last 12 months
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Being tested
- Probiotic Supplement
- Keywords
- Probiotics, Isoagglutinins, Anti-A, Anti-B, Hemolysis, Healthy Volunteer, HV
- Medical subject headings
- Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic SupplementDietary supplement
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in isoagglutinin titer
Secondary outcomes (1)
Dose-response relationship between probiotic dose and peak change in isoagglutinin titer.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2009 (estimated)
- Study start28 Apr 2009
- Primary completion6 Apr 2011
- Study completion6 Apr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Isoagglutinin-Mediated HemolysisStudies 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
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Investigators
- Susan F Leitman, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00891787
- Sponsor's protocol ID
- 090135
- Other IDs
- 09-CC-0135
- Status last verified
- 10 Apr 2014
- First submitted
- 30 Apr 2009
- Last updated
- 6 Oct 2017
- Results posted
- No
Publications
Snelling AM. Effects of probiotics on the gastrointestinal tract. Curr Opin Infect Dis. 2005 Oct;18(5):420-6. doi: 10.1097/01.qco.0000182103.32504.e3.
PubMed 16148529Springer GF, Horton RE, Forbes M. Origin of anti-human blood group B agglutinins in white Leghorn chicks. J Exp Med. 1959 Aug 1;110(2):221-44. doi: 10.1084/jem.110.2.221.
PubMed 13673136SPRINGER GF, ANSELL N, BRANDES W, NORRIS RF. Relation of blood group specific substances from bacilli and a higher plant to hemagglutinin formation. Bibl Haematol. 1958;7:190-5. doi: 10.1159/000427094. No abstract available.
PubMed 13499259
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Probiotic Ingestion and Isoagglutinin Titers
- ClinicalTrials.gov ID
- NCT00891787
- Acronym / sponsor ID
- 090135
- Keywords
- Probiotics, Isoagglutinins, Anti-A, Anti-B, Hemolysis, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 28 Apr 2009
- Primary completion
- 6 Apr 2011 (actual)
- Study completion
- 6 Apr 2011 (actual)
- First posted
- 1 May 2009 (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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- AST/ALT less than or equal to 2 times ULN; creatinine less than or equal to ULN; hemoglobin greater than or equal to 12.5 g/dL (males and females)
Key exclusion criteria (13 listed)
- ABO blood group of AB
- Current apheresis platelet donor in the NIH DTM
- Current or past history of gastrointestinal disease or surgery including: Crohn s disease, ulcerative colitis, celiac disease, irritable bowel syndrome, gastric bypass or banding, esophagectomy, gastrectomy, small bowel resection, colectomy, and any history of gastrointestinal malignancy including pancreatic carcinoma
- Vaccination within the last 2 months, with the exception of the influenza vaccine
- A history of high risk behaviors for exposure to HIV, HBV, HCV, HTLV (no intravenous drug use in past 5 years, no male sex with males in last 5 years)
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 |
|---|---|---|
| Probiotic Supplement | Dietary supplement | – |
Primary outcome
Changes in isoagglutinin titer
1 secondary outcome
Dose-response relationship between probiotic dose and peak change in isoagglutinin titer.
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 6 Oct 2017.
- Background: PubMed 16148529Snelling AM. Effects of probiotics on the gastrointestinal tract. Curr Opin Infect Dis. 2005 Oct;18(5):420-6. doi: 10.1097/01.qco.0000182103.32504.e3.
- Background: PubMed 13673136Springer GF, Horton RE, Forbes M. Origin of anti-human blood group B agglutinins in white Leghorn chicks. J Exp Med. 1959 Aug 1;110(2):221-44. doi: 10.1084/jem.110.2.221.
- Background: PubMed 13499259SPRINGER GF, ANSELL N, BRANDES W, NORRIS RF. Relation of blood group specific substances from bacilli and a higher plant to hemagglutinin formation. Bibl Haematol. 1958;7:190-5. doi: 10.1159/000427094. No abstract available.
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.
Susan F Leitman, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
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 Probiotic Supplement in people with Isoagglutinin-Mediated Hemolysis and Probiotic Toxicity, run by National Institutes of Health Clinical Center (CC) 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 6 inclusion and 13 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 6 Oct 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. 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?
Changes in isoagglutinin titer. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00891787, which also lists 3 linked publications.
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 6 Oct 2017.