Disorder of Vitamin B12NCT00235573
Evaluation of Holotranscobalamin as an Indicator of Vitamin B12 Absorption
A study testing Vitamin B12 in people with Disorder of Vitamin B12, run by University of Florida at 1 site in United States.
Trial summary
Vitamin B12 is an essential nutrient that the body needs for cells to divide and function normally. Individuals may develop a deficiency of vitamin B12 by either limiting the amount in the diet or by decreased vitamin B12 intake into the body (absorption). Keeping adequate B12 blood levels is important for health. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Disorder of Vitamin B12
- What is being tested?
- Vitamin B12
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Nov 2005
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- No vitamin B12-containing supplement use within past year
- No vitamin B12 injections within past year
- No use of tobacco products
- No chronic use of prescription medications except oral contraceptives
- No history of chronic disease (e.g., pernicious anemia, cancer, diabetes, renal disease, hypertension, neurological abnormalities, gastrointestinal disorders)
- BMI between 18.5-29.9
Show all 10Show fewer
- General Chemistry Blood Tests (all values within or near normal range; hemoglobin if female ≥ 11.0 g/dL; if male ≥ 12 g/dL)
- B12 status (Serum B12 ≥ 444 pmol/L)
- Capable of understanding the informed consent form
- Agrees to comply with protocol requirements
Who cannot join
- History of pernicious anemia, cancer, diabetes, renal disease, hypertension, heart disease, neurological abnormalities, gastrointestinal disorders, lung disease, hepatic disease, hematologic, or other metabolic diseases that, in the opinion of the Co-Principal Investigators, would affect safety or compliance
- Vitamin B12 supplement use or injections within past year
- Pregnant or breast feeding
- Has BMI <18.5 or >29.9
- Has donated or lost a significant volume (>450 mL) of blood or plasma within 30 days of the study
- General chemistry lab values outside of ranges
Show all 11Show fewer
- Serum B12 outside of range listed above
- Use of tobacco products
- Chronic use of prescription medications except oral contraceptives
- Does not understand the informed consent form
- Does not agree to comply with protocol requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
General Clinical Research Center, Shands Hospital, University of Florida
Gainesville, Florida, 32610-0322
About this study
Vitamin B12 is an essential nutrient that the body needs for cells to divide and function normally. Individuals may develop a deficiency of vitamin B12 by either limiting the amount in the diet or by decreased vitamin B12 intake into the body (absorption). Keeping adequate B12 blood levels is important for health. Vitamin B12 deficiency may increase one's risk for developing anemia and can even lead to neurological problems and paralysis if the deficiency is severe and lasts a long time. It is very important for doctors to have accurate tests to determine if people are absorbing vitamin B12 normally so that treatment can be started before severe clinical problems occur.
The purpose of this research is to provide new information that may help scientists develop a better method to test for problems with absorbing vitamin B12. In this study, changes in the amounts of vitamin B12 bound to protein (transcobalamin) in the blood will be measured after doses of vitamin B12 are taken. If the amounts of this vitamin B12-protein complex (called holo-transcobalamin) change in response to taking a vitamin B12 supplement in normal individuals, it may be possible to use this information to develop a new sensitive test to identify individuals who have problems absorbing vitamin B12. This new vitamin B12 absorption test may be a better clinical test for vitamin B12 absorption than those now available for doctors to use.
Read the detailed description
Part I Screening: Individuals who meet initial screening criteria will be scheduled to have fasting blood samples drawn in the General Clinical Research Center (GCRC). All participants will sign informed consent forms approved by the UF Institutional Review Board prior to the initiation of this part of the study. Subjects' heights and weights will be measured and subjects will be asked to complete a medical history questionnaire. Blood analyses will include serum B12, blood chemistry, and hematological indices. Females will be given a pregnancy test. Subjects eligible for Part II of the study (Intervention) will have serum B12 concentrations that are ≥444 pmol/L; will be non-anemic; and will have normal general blood chemistry (all values within or near the normal range), and no history of chronic disease (e.g., pernicious anemia, cancer, diabetes, renal disease, hypertension, neurological abnormalities, gastrointestinal disorders). Any subject with deficient (<148 pmol/L) serum B12 concentration [18] will not be eligible for participation and will be instructed to see their personal physician for complete follow-up and treatment.
Part II Intervention: Changes in B12 status assessment indicators in response to B12 supplementation will be evaluated.
Subjects will come to the GCRC the night before (Day 1) the intervention protocol. The next morning (Day 1) following an overnight fast, an indwelling catheter will be inserted from which repeated blood samples will be drawn throughout Day 1. A baseline fasting blood sample (#1) will be drawn. Subjects will then consume a light breakfast (including 1 piece of bread and 8 oz of orange juice) and will take a 9 ug dose of B12 (Dose 1). Thirty minutes after completion of the meal and consumption of the B12 supplement, a second blood sample (#2) will be drawn. Five subsequent hourly blood samples (# 3-7) will be drawn. After the 7th blood sample the subjects will consume one piece of bread and 8 ounces of orange juice and will take a second 9 ug dose of B12 (Dose 2) and have a blood sample (#8) drawn 30 minutes after consumption of the meal and the B12 dose. Five subsequent hourly blood samples (#9-13) will be drawn. The subjects will then consume one piece of bread and 8 ounces of orange juice and take a 9 ug dose of B12 (Dose 3). Another blood sample (#14) will be drawn 30 minutes after the meal and the B12 dose. One hour later, a final (Day 1) blood sample (#15) will be drawn followed by removal of the catheter. In addition to the bread and juice consumed with each B12 supplement, subjects will receive a mid-morning snack 2 hours after Dose 1 of the B12 supplement, lunch 3.5 hrs after Dose 1 of the B12 supplement, dinner at 4 hours after Dose 2 of the B12 supplement, and an evening snack at 3 hours after Dose 3. Low B12-containing foods will be provided in the GCRC. Water and non-caffeinated, non-caloric beverages will be allowed ad libitum.
The subjects will remain in the GCRC overnight and a fasting blood sample (#16) will be drawn in the morning on Day 2. On Day 2 participants will be provided breakfast following the blood draw, after which they will be free to leave the GCRC. Subjects will be provided with take-away meals and snacks (lunch, dinner, snacks) consisting of low-B12 containing foods.
Subjects will be instructed to return on the morning of Day 3 at which time they will have one am fasting blood sample (#17) drawn and will be provided with breakfast before they leave the GCRC. All overnight fasts will be from 10 pm the previous night. The following B12 indicators will be measured at each blood draw (a) holo-TC; (b) total-TC; (c) holo-HC and total HC; (d) serum B12; and (e) plasma albumin. Additional B12 status indicators (e.g. homocysteine, methylmalonic acid, RBC B12) will be measured at select blood draw intervals. A baseline folate analysis will be done.
- Conditions
- Disorder of Vitamin B12
- Being tested
- Vitamin B12
- Keywords
- Vitamin B12 absorption, Holo-transcobalamin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin B12Dietary supplement
After taking a fasting blood sample, all subjects were given a light breakfast plus 9 micrograms of vitamin B12. Two more doses of vitamin B12, 9 micrograms each, were administered 6 hours apart.
| Study group | Role | What they receive |
|---|---|---|
| Vitamin B12 supplement | Experimental | After taking a fasting blood sample, all subjects were given a light breakfast plus 9 micrograms of vitamin B12. Two more doses of vitamin B12 were administered 6 hours apart. Receives: Dietary Supplement: Vitamin B12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Holo-transcobalamin
Holo-TC is a vitamin B12 carrier protein. Only vitamin B12 bound to holo-TC can be taken up by cells. Changes in holo-TC after an oral dose of vitamin B12 may provide a clinical test to assess vitamin B12 absorption. The change in holo-transcobalamin (holo-TC) from baseline was measured at timed intervals in response to supplemental vitamin B12 and compared to baseline. The purpose was to ascertain the time point at which holo-TC reaches the maximum concentration in the blood following a dose of vitamin B12 in subjects without defects in vitamin B12 absorption.
Measured: Holo-transcobalamin measured at 24 hours after baseline
Secondary outcomes (1)
Total Transcobalamin Measured at Intervals From Baseline to 48 Hours.
Measured: Baseline through 48 hours at intervals of 0, 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, 6, 7, 8, 9, 10, 11, 11.5, 12.5, 24, 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2005 (estimated)
- Study startOct 2005
- Primary completionNov 2005
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Disorder of Vitamin B12Studies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Research Resources (NCRR)
- Responsible party
- Sponsor
- Investigators
- Lynn B Bailey, PhD, Principal investigator, University of FloridaGail PA Kauwell, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00235573
- Sponsor's protocol ID
- 433-2005
- Other IDs
- 7591, M01RR000082
- Status last verified
- Dec 2011
- First submitted
- 6 Oct 2005
- Last updated
- 22 Dec 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
von Castel-Dunwoody KM, Kauwell GP, Shelnutt KP, Vaughn JD, Griffin ER, Maneval DR, Theriaque DW, Bailey LB. Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism. Am J Clin Nutr. 2005 Jun;81(6):1436-41. doi: 10.1093/ajcn/81.6.1436.
PubMed 15941899Bor MV, Nexo E, Hvas AM. Holo-transcobalamin concentration and transcobalamin saturation reflect recent vitamin B12 absorption better than does serum vitamin B12. Clin Chem. 2004 Jun;50(6):1043-9. doi: 10.1373/clinchem.2003.027458. Epub 2004 Mar 25.
PubMed 15044317Bor MV, Cetin M, Aytac S, Altay C, Nexo E. Nonradioactive vitamin B12 absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B12. Clin Chem. 2005 Nov;51(11):2151-5. doi: 10.1373/clinchem.2005.055509. Epub 2005 Sep 15.
PubMed 16166166
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Holotranscobalamin as an Indicator of Vitamin B12 Absorption
- ClinicalTrials.gov ID
- NCT00235573
- Acronym / sponsor ID
- 433-2005
- Conditions
- Disorder of Vitamin B12
- Keywords
- Vitamin B12 absorption, Holo-transcobalamin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Oct 2005
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 10 Oct 2005 (estimated)
- Results
- Posted 14 Dec 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vitamin B12 is an essential nutrient that the body needs for cells to divide and function normally. Individuals may develop a deficiency of vitamin B12 by either limiting the amount in the diet or by decreased vitamin B12 intake into the body (absorption). Keeping adequate B12 blood levels is important for health. Vitamin B12 deficiency may increase one's risk for developing anemia and can even lead to neurological problems and paralysis if the deficiency is severe and lasts a long time. It is very important for doctors to have accurate tests to determine if people are absorbing vitamin B12 normally so that treatment can be started before severe clinical problems occur.
The purpose of this research is to provide new information that may help scientists develop a better method to test for problems with absorbing vitamin B12. In this study, changes in the amounts of vitamin B12 bound to protein (transcobalamin) in the blood will be measured after doses of vitamin B12 are taken. If the amounts of this vitamin B12-protein complex (called holo-transcobalamin) change in response to taking a vitamin B12 supplement in normal individuals, it may be possible to use this information to develop a new sensitive test to identify individuals who have problems absorbing vitamin B12. This new vitamin B12 absorption test may be a better clinical test for vitamin B12 absorption than those now available for doctors to use.
Detailed description
Part I Screening: Individuals who meet initial screening criteria will be scheduled to have fasting blood samples drawn in the General Clinical Research Center (GCRC). All participants will sign informed consent forms approved by the UF Institutional Review Board prior to the initiation of this part of the study. Subjects' heights and weights will be measured and subjects will be asked to complete a medical history questionnaire. Blood analyses will include serum B12, blood chemistry, and hematological indices. Females will be given a pregnancy test. Subjects eligible for Part II of the study (Intervention) will have serum B12 concentrations that are ≥444 pmol/L; will be non-anemic; and will have normal general blood chemistry (all values within or near the normal range), and no history of chronic disease (e.g., pernicious anemia, cancer, diabetes, renal disease, hypertension, neurological abnormalities, gastrointestinal disorders). Any subject with deficient (<148 pmol/L) serum B12 concentration [18] will not be eligible for participation and will be instructed to see their personal physician for complete follow-up and treatment.
Part II Intervention: Changes in B12 status assessment indicators in response to B12 supplementation will be evaluated.
Subjects will come to the GCRC the night before (Day 1) the intervention protocol. The next morning (Day 1) following an overnight fast, an indwelling catheter will be inserted from which repeated blood samples will be drawn throughout Day 1. A baseline fasting blood sample (#1) will be drawn. Subjects will then consume a light breakfast (including 1 piece of bread and 8 oz of orange juice) and will take a 9 ug dose of B12 (Dose 1). Thirty minutes after completion of the meal and consumption of the B12 supplement, a second blood sample (#2) will be drawn. Five subsequent hourly blood samples (# 3-7) will be drawn. After the 7th blood sample the subjects will consume one piece of bread and 8 ounces of orange juice and will take a second 9 ug dose of B12 (Dose 2) and have a blood sample (#8) drawn 30 minutes after consumption of the meal and the B12 dose. Five subsequent hourly blood samples (#9-13) will be drawn. The subjects will then consume one piece of bread and 8 ounces of orange juice and take a 9 ug dose of B12 (Dose 3). Another blood sample (#14) will be drawn 30 minutes after the meal and the B12 dose. One hour later, a final (Day 1) blood sample (#15) will be drawn followed by removal of the catheter. In addition to the bread and juice consumed with each B12 supplement, subjects will receive a mid-morning snack 2 hours after Dose 1 of the B12 supplement, lunch 3.5 hrs after Dose 1 of the B12 supplement, dinner at 4 hours after Dose 2 of the B12 supplement, and an evening snack at 3 hours after Dose 3. Low B12-containing foods will be provided in the GCRC. Water and non-caffeinated, non-caloric beverages will be allowed ad libitum.
The subjects will remain in the GCRC overnight and a fasting blood sample (#16) will be drawn in the morning on Day 2. On Day 2 participants will be provided breakfast following the blood draw, after which they will be free to leave the GCRC. Subjects will be provided with take-away meals and snacks (lunch, dinner, snacks) consisting of low-B12 containing foods.
Subjects will be instructed to return on the morning of Day 3 at which time they will have one am fasting blood sample (#17) drawn and will be provided with breakfast before they leave the GCRC. All overnight fasts will be from 10 pm the previous night. The following B12 indicators will be measured at each blood draw (a) holo-TC; (b) total-TC; (c) holo-HC and total HC; (d) serum B12; and (e) plasma albumin. Additional B12 status indicators (e.g. homocysteine, methylmalonic acid, RBC B12) will be measured at select blood draw intervals. A baseline folate analysis will be done.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vitamin B12 supplement | Experimental | Dietary Supplement: Vitamin B12After taking a fasting blood sample, all subjects were given a light breakfast plus 9 micrograms of vitamin B12. Two more doses of vitamin B12 were administered 6 hours apart. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- No vitamin B12-containing supplement use within past year
- No vitamin B12 injections within past year
- No use of tobacco products
- No chronic use of prescription medications except oral contraceptives
- No history of chronic disease (e.g., pernicious anemia, cancer, diabetes, renal disease, hypertension, neurological abnormalities, gastrointestinal disorders)
Key exclusion criteria (11 listed)
- History of pernicious anemia, cancer, diabetes, renal disease, hypertension, heart disease, neurological abnormalities, gastrointestinal disorders, lung disease, hepatic disease, hematologic, or other metabolic diseases that, in the opinion of the Co-Principal Investigators, would affect safety or compliance
- Vitamin B12 supplement use or injections within past year
- Pregnant or breast feeding
- Has BMI <18.5 or >29.9
- Has donated or lost a significant volume (>450 mL) of blood or plasma within 30 days of the study
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 |
|---|---|---|
| Vitamin B12After taking a fasting blood sample, all subjects were given a light breakfast plus 9 micrograms of vitamin B12. Two more doses of vitamin B12, 9 micrograms each, were administered 6 hours apart. | Dietary supplement | Vitamin B12 supplement |
Primary outcome
Change in Holo-transcobalamin
Time frame: Holo-transcobalamin measured at 24 hours after baseline
Holo-TC is a vitamin B12 carrier protein. Only vitamin B12 bound to holo-TC can be taken up by cells. Changes in holo-TC after an oral dose of vitamin B12 may provide a clinical test to assess vitamin B12 absorption. The change in holo-transcobalamin (holo-TC) from baseline was measured at timed intervals in response to supplemental vitamin B12 and compared to baseline. The purpose was to ascertain the time point at which holo-TC reaches the maximum concentration in the blood following a dose of vitamin B12 in subjects without defects in vitamin B12 absorption.
1 secondary outcome
Total Transcobalamin Measured at Intervals From Baseline to 48 Hours.
Time frame: Baseline through 48 hours at intervals of 0, 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, 6, 7, 8, 9, 10, 11, 11.5, 12.5, 24, 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15941899von Castel-Dunwoody KM, Kauwell GP, Shelnutt KP, Vaughn JD, Griffin ER, Maneval DR, Theriaque DW, Bailey LB. Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism. Am J Clin Nutr. 2005 Jun;81(6):1436-41. doi: 10.1093/ajcn/81.6.1436.
- Background: PubMed 15044317Bor MV, Nexo E, Hvas AM. Holo-transcobalamin concentration and transcobalamin saturation reflect recent vitamin B12 absorption better than does serum vitamin B12. Clin Chem. 2004 Jun;50(6):1043-9. doi: 10.1373/clinchem.2003.027458. Epub 2004 Mar 25.
- Background: PubMed 16166166Bor MV, Cetin M, Aytac S, Altay C, Nexo E. Nonradioactive vitamin B12 absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B12. Clin Chem. 2005 Nov;51(11):2151-5. doi: 10.1373/clinchem.2005.055509. Epub 2005 Sep 15.
- The website for the UF General Clinical Research Center Clinical and Translational Science InstituteLink provided by the sponsor.
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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.
Lynn B Bailey, PhD principal investigator
University of Florida
Gail PA Kauwell, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin B12 in people with Disorder of Vitamin B12, run by University of Florida 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 10 inclusion and 11 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 22 Dec 2011. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Holo-transcobalamin (time frame: Holo-transcobalamin measured at 24 hours after baseline). 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 NCT00235573, 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 22 Dec 2011.