AnemiaPhase 1NCT01572506
Mechanisms Accounting for Unexplained Anemia in the Elderly
A Phase 1 study testing Biotin RBC survival in people with Anemia, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
Background: Anemia occurs commonly and is associated with poor outcomes in the elderly. In about a third of anemia cases in older people (over age 65), the cause of anemia is unexplained. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anemia
- What is being tested?
- Biotin RBC survival
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2012to 30 Jul 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ambulatory, community dweller
- Age greater than or equal to 70 years or older or between the ages of 18 and 50 years.
- Able to understand English
- Able to complete study questionnaires as determined by the investigator
- Evidence for recent (within 1 year) clinical evaluation for blood loss directed by primary care physician or consultant in subjects referred with microcytic anemia or with referring laboratories indicative of iron deficiency. Furthermore, subjects found to have microcytic anemia will be eligible but will be referred to their primary doctor for evaluation of blood loss.
- Provide informed consent
Who cannot join
- Hemoglobin (Hb) less than 9 g/dL during screening
- History of red blood cell transfusion withinthe 3 month period prior to accrual to this study, or evidence for active bleeding as ascertained by medical history (e.g., persistent melena, hematuria or dysfunctional uterine bleeding).
- Patients for whom oral iron supplementation has been prescribed within the past two months. (Patients on a stable dose of oral iron for more than two months may be eligible).
- ALT or AST more than 3 times upper normal limitation of the time of screening
- B12 or folate deficiencies during screening period
- Estimated GFR less than 30 ml/min/1.73m(2)during screening period (by the 4-variable Modification of Diet in Renal Disease [MDRD] equation).
Show all 20Show fewer
- Receiving hemodialysis or peritoneal dialysis for renal failure, or history of kidney transplant
- Use of exogenous erythropoietin during the past 3 months
- Any major surgery requiring general anesthesia within the past 3 months
- Treatment with chemotherapy or radiotherapy in the past 12 months
- Current diagnosis of active cancer, other than non-melanoma skin cancer and, stable prostate cancer
- History of blood disorders including thalassemia, sickle cell disease or myelodysplasia
- Current severe (NYHA Class III - IV) congestive heart failure or advanced chronic obstructive pulmonary disease
- Positive serum monoclonal protein and immunofixation
- Women who are pregnant or women planning to get pregnant during the duration of the study or those with a positive pregnancy test during screening
- Active infection requiring antibiotic treatment or HIV, Hepatitis B or C
- History of overt chronic inflammation, active Crohn s disease, rheumatoid arthritis, or diabetes(HbA1C greater than 7),
- Known hemolytic anemia
- History of prosthetic heart valve
- History of participation in biotinylation studies or handling biotinylated reagent products.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, 21224
About this study
Official title: Assessing Mechanisms Accounting for Unexplained Anemia in the Elderly
Background:
- Anemia occurs commonly and is associated with poor outcomes in the elderly. In about a third of anemia cases in older people (over age 65), the cause of anemia is unexplained. Anemia in older adults may be caused by the bone marrow's inability to produce red blood cells fast enough to replace older red blood cells that have died. Researchers want to look at unexplained anemia by studying the life span of red blood cells in younger adults and older adults. To do so, a vitamin called Biotin will be used as a marker on the red blood cells.
Read more
Objectives:
- To investigate possible causes of unexplained anemia in older people.
Eligibility:
- Individuals in the following groups:
- Men and women between 18 and 50 years of age who do not have anemia
- Men and women at least 70 years of age who do not have anemia.
- Men and women at least 70 years of age who have iron-deficiency anemia.
- Men and women at least 70 years of age who have anemia with no known cause.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- Participants will have an overnight stay for the first study visit. They will provide a blood sample to which Biotin will be added. The blood sample with Biotin will then be returned to the participant. Twenty-four hours later, another blood sample will be collected.
- Participants will have up to 14 additional study visits. At each visit, blood samples will be collected to measure the amount of Biotin remaining in the blood.
- Participants may also provide a separate blood sample for genetic testing. These tests may provide more information about genetic causes of unexplained anemia.
Read the detailed description
Anemia occurs commonly and is associated with adverse outcomes in the elderly. In approximately one third of anemia cases in patients over the age of 65 years, the cause of anemia is not readily apparent (unexplained anemia or UA). Of the various causes of anemia in young adults, overt hemolysis (either acute or chronic) is very uncommon. However, we speculate that older persons tend to develop a low grade hemolytic process which significantly reduces RBC survival, and when this is not adequately countered by increased bone marrow RBC production, anemia (UA) is the consequence. This hypothesis is supported by a few clinical observations. For example, red cells in patients with UA are generally not small and when the peripheral blood smear is examined microscopically, anisocytosis (varying cell size) is observed, as is typical in patients with hemolytic anemia. Similarly, UA is frequently associated with an elevated red cell distribution width (RDW) on electronic measurement. Furthermore, serum erythropoietin levels gradually rise with advancing age (1), and this would be consistent either with a smoldering hemolytic process or a decreased responsiveness to erythropoietin. To address the hypothesis that UA is due, at least in part, to shortened RBC survival, we propose to directly measure red blood cell survival and to correlate this with aspects of red blood cell physiology that may increase susceptibility to the hemolytic process.
- Conditions
- Anemia
- Being tested
- Biotin RBC survival
- Keywords
- Anemia, Elderly, Mechanisms, Red Cell Survival
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biotin RBC survivalDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Age 70 and older with unexplained anemia Receives: Drug: Biotin RBC survival |
| Group 2 | Active comparator | Age 70 and older with iron deficient anemia Receives: Drug: Biotin RBC survival |
| Group 3 | Active comparator | Age 70 and older without anemia Receives: Drug: Biotin RBC survival |
| Group 4 | Active comparator | Age 18 - 50 without anemia Receives: Drug: Biotin RBC survival |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of red blood cell survival
Directly measure red blood cell survival and to correlate this with aspects of red blood cell physiology that may increase susceptibilty to the hemolytic process
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2012 (estimated)
- Study start29 Mar 2012
- Primary completion30 Jul 2015
- Study completion30 Jul 2015
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 AnemiaStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Josephine M Egan, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01572506
- Sponsor's protocol ID
- 999912109
- Other IDs
- 12-AG-N109
- Status last verified
- Jul 2026
- First submitted
- 5 Apr 2012
- Last updated
- 29 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The NIA IRP is discussing the plan to make IPD available. A final decision has not been made.
Publications
Ershler WB, Sheng S, McKelvey J, Artz AS, Denduluri N, Tecson J, Taub DD, Brant LJ, Ferrucci L, Longo DL. Serum erythropoietin and aging: a longitudinal analysis. J Am Geriatr Soc. 2005 Aug;53(8):1360-5. doi: 10.1111/j.1532-5415.2005.53416.x.
PubMed 16078962Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004 Oct 15;104(8):2263-8. doi: 10.1182/blood-2004-05-1812. Epub 2004 Jul 6.
PubMed 15238427Artz AS, Fergusson D, Drinka PJ, Gerald M, Gravenstein S, Lechich A, Silverstone F, Finnigan S, Janowski MC, McCamish MA, Ershler WB. Prevalence of anemia in skilled-nursing home residents. Arch Gerontol Geriatr. 2004 Nov-Dec;39(3):201-6. doi: 10.1016/j.archger.2004.03.006.
PubMed 15381339
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Mechanisms Accounting for Unexplained Anemia in the Elderly
- ClinicalTrials.gov ID
- NCT01572506
- Acronym / sponsor ID
- 999912109
- Conditions
- Anemia
- Keywords
- Anemia, Elderly, Mechanisms, Red Cell Survival
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 29 Mar 2012 (actual)
- Primary completion
- 30 Jul 2015 (actual)
- Study completion
- 30 Jul 2015 (actual)
- First posted
- 6 Apr 2012 (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:
- Anemia occurs commonly and is associated with poor outcomes in the elderly. In about a third of anemia cases in older people (over age 65), the cause of anemia is unexplained. Anemia in older adults may be caused by the bone marrow's inability to produce red blood cells fast enough to replace older red blood cells that have died. Researchers want to look at unexplained anemia by studying the life span of red blood cells in younger adults and older adults. To do so, a vitamin called Biotin will be used as a marker on the red blood cells.
Objectives:
- To investigate possible causes of unexplained anemia in older people.
Eligibility:
- Individuals in the following groups:
- Men and women between 18 and 50 years of age who do not have anemia
- Men and women at least 70 years of age who do not have anemia.
- Men and women at least 70 years of age who have iron-deficiency anemia.
- Men and women at least 70 years of age who have anemia with no known cause.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- Participants will have an overnight stay for the first study visit. They will provide a blood sample to which Biotin will be added. The blood sample with Biotin will then be returned to the participant. Twenty-four hours later, another blood sample will be collected.
- Participants will have up to 14 additional study visits. At each visit, blood samples will be collected to measure the amount of Biotin remaining in the blood.
- Participants may also provide a separate blood sample for genetic testing. These tests may provide more information about genetic causes of unexplained anemia.
Detailed description
Anemia occurs commonly and is associated with adverse outcomes in the elderly. In approximately one third of anemia cases in patients over the age of 65 years, the cause of anemia is not readily apparent (unexplained anemia or UA). Of the various causes of anemia in young adults, overt hemolysis (either acute or chronic) is very uncommon. However, we speculate that older persons tend to develop a low grade hemolytic process which significantly reduces RBC survival, and when this is not adequately countered by increased bone marrow RBC production, anemia (UA) is the consequence. This hypothesis is supported by a few clinical observations. For example, red cells in patients with UA are generally not small and when the peripheral blood smear is examined microscopically, anisocytosis (varying cell size) is observed, as is typical in patients with hemolytic anemia. Similarly, UA is frequently associated with an elevated red cell distribution width (RDW) on electronic measurement. Furthermore, serum erythropoietin levels gradually rise with advancing age (1), and this would be consistent either with a smoldering hemolytic process or a decreased responsiveness to erythropoietin. To address the hypothesis that UA is due, at least in part, to shortened RBC survival, we propose to directly measure red blood cell survival and to correlate this with aspects of red blood cell physiology that may increase susceptibility to the hemolytic process.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: Biotin RBC survivalAge 70 and older with unexplained anemia |
| Group 2 | Active comparator | Drug: Biotin RBC survivalAge 70 and older with iron deficient anemia |
| Group 3 | Active comparator | Drug: Biotin RBC survivalAge 70 and older without anemia |
| Group 4 | Active comparator | Drug: Biotin RBC survivalAge 18 - 50 without anemia |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Ambulatory, community dweller
- Age greater than or equal to 70 years or older or between the ages of 18 and 50 years.
- Able to understand English
- Able to complete study questionnaires as determined by the investigator
- Evidence for recent (within 1 year) clinical evaluation for blood loss directed by primary care physician or consultant in subjects referred with microcytic anemia or with referring laboratories indicative of iron deficiency. Furthermore, subjects found to have microcytic anemia will be eligible but will be referred to their primary doctor for evaluation of blood loss.
Key exclusion criteria (20 listed)
- Hemoglobin (Hb) less than 9 g/dL during screening
- History of red blood cell transfusion withinthe 3 month period prior to accrual to this study, or evidence for active bleeding as ascertained by medical history (e.g., persistent melena, hematuria or dysfunctional uterine bleeding).
- Patients for whom oral iron supplementation has been prescribed within the past two months. (Patients on a stable dose of oral iron for more than two months may be eligible).
- ALT or AST more than 3 times upper normal limitation of the time of screening
- B12 or folate deficiencies during screening period
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 |
|---|---|---|
| Biotin RBC survival | Drug | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
Measurement of red blood cell survival
Directly measure red blood cell survival and to correlate this with aspects of red blood cell physiology that may increase susceptibilty to the hemolytic process
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 29 Jul 2026.
- Background: PubMed 16078962Ershler WB, Sheng S, McKelvey J, Artz AS, Denduluri N, Tecson J, Taub DD, Brant LJ, Ferrucci L, Longo DL. Serum erythropoietin and aging: a longitudinal analysis. J Am Geriatr Soc. 2005 Aug;53(8):1360-5. doi: 10.1111/j.1532-5415.2005.53416.x.
- Background: PubMed 15238427Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004 Oct 15;104(8):2263-8. doi: 10.1182/blood-2004-05-1812. Epub 2004 Jul 6.
- Background: PubMed 15381339Artz AS, Fergusson D, Drinka PJ, Gerald M, Gravenstein S, Lechich A, Silverstone F, Finnigan S, Janowski MC, McCamish MA, Ershler WB. Prevalence of anemia in skilled-nursing home residents. Arch Gerontol Geriatr. 2004 Nov-Dec;39(3):201-6. doi: 10.1016/j.archger.2004.03.006.
- Individual participant dataSharing planned: Undecided. The NIA IRP is discussing the plan to make IPD available. A final decision has not been made.
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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.
Josephine M Egan, M.D. principal investigator
National Institute on Aging (NIA)
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 Biotin RBC survival in people with Anemia, run by National Institute on Aging (NIA) 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 20 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 29 Jul 2026. 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?
Measurement of red blood cell survival. 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 NCT01572506, 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 29 Jul 2026.