Sickle Cell AnemiaNCT02258997
Hepcidin Levels in Sickle Cell Disease (SCD)
An observational study of Sickle Cell Anemia and Sickle - Beta Thalassemia, run by Kenneth Ataga, MD.
Trial summary
The investigators propose that patients with HbSβ-thalassemia have lower levels of hepcidin and higher levels of GDF-15 than HbSS patients during the non-crisis, "steady states." In addition, the investigators propose that when controlled for RBC transfusion, patients with HbSβ-thalassemia will have higher levels of… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Sickle Cell Anemia, Sickle - Beta Thalassemia
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- Mar 2014to Sep 2015
- Phase
- Observational
- 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
Study population: Subjects will be recruited from the population followed in the Adult Sickle Cell Clinic with either HbSS or HbS-βthalassemia who meet the eligibility criteria for the study.
Who may be able to join
- age 18 - 70 years
- confirmed diagnosis of HbSS or HbS-β thalassemia
- no history of acute vaso-occlusive event (acute pain crisis or acute chest syndrome) requiring emergency room visit or hospitalization over the preceding 4 weeks
- clinically acceptable physical examination and vital signs
- ability of patient or legal representative to understand the requirements of the study and willingness to sign the Informed Consent document.
Who cannot join
- pregnancy or breastfeeding
- current acute illness, including a painful crisis
- iron deficiency anemia
- history of liver disease with alanine aminotransferase (ALT) ≥ 3 X upper limit of normal (ULN)
- history of hereditary hemochromatosis, connective tissues disease, chronic inflammatory, disorder, or malignancy
- chronic transfusion program or any transfusion within the previous 3 months
About this study
The investigators propose that patients with HbSβ-thalassemia have lower levels of hepcidin and higher levels of GDF-15 than HbSS patients during the non-crisis, "steady states." In addition, the investigators propose that when controlled for RBC transfusion, patients with HbSβ-thalassemia will have higher levels of storage iron (based on serum ferritin).
Participants: Total number of subjects is 42 - 21 subjects with HbSS, and 21 subjects with HbSβ-thalassemia ).
Procedures (methods): Eligible subjects with documented SCD (HbSS, HbS-β 0-thalassemia or HbS-β+-thalassemia) followed at the University of North Carolina (UNC) Comprehensive Sickle Cell Program will be evaluated in this single-center, prospective, cross-sectional study. The patients will be screened for eligibility at the time of a routine sickle cell clinic visit. Patients' data will be obtained in person at the time of evaluation and through review of their medical records. Investigators will obtain information on SCD-related clinical complications and obtain an estimate of the number of lifetime RBC transfusions. Blood samples will be obtained for laboratory tests. Plasma samples for hepcidin, growth differentiation factor 15 (GDF -15), and high-sensitivity CRP will be stored at -80 degrees Celsius until analysis. Other routine laboratory studies including complete blood count (CBC) with differential and reticulocyte count, serum iron profile and ferritin, and liver function tests will be performed at the clinical laboratories of UNC Hospitals.The subjects will have 30 ml. of blood drawn for this research study. Females of child bearing potential will have a urine pregnancy test at the time of the study.
Read the detailed description
Sickle cell disease (SCD) refers to a group of inherited disorders characterized by the presence of sickle hemoglobin (HbS) that are associated with episodes of acute illness and progressive organ damage. The most common variant of SCD, sickle cell anemia (HbSS), refers to homozygosity for the β S allele, with most of the remaining patients having sickle hemoglobin C disease (HbSC) and sickle beta thalassemia (HbSβ-thalassemia).
SCD may be associated with iron overload that occurs following repeated red blood cell (RBC) transfusions. However, in patients with beta thalassemia major, iron overload occurs due to both repeated RBC transfusions and hyperabsorption of iron. The hyperabsorption of iron in beta thalassemia occurs due to ineffective erythropoiesis and subsequent downregulation of hepcidin. Thalassemia intermedia and major are the most studied human models of hepcidin modulation by ineffective erythropoiesis alone and the combined and opposite effect of both ineffective erythropoiesis and transfusion dependent iron overload, accordingly. Regular transfusions induce massive iron loading but inhibit erythropoietic drive. Accordingly, hepcidin production is higher in thalassemia major than in thalassemia intermedia although still inappropriate to the massive transfusional iron loading that partially counteracts the erythropoietic-dependent hepcidin down-regulation (Origa R et al, 2007; Kattamis A et al, 2006; Camberlein E et al, 2008). No differences in the steady-state levels of hepcidin was observed when HbSS patients (N = 40) were compared with healthy hemoglobin AA (HbAA)controls (N = 30) (85.3 ± 30 l μg/L vs. 83.5 ± 40 l μg/L) (Ezeh C et al, 2005).
Hepcidin is a 25-amino acid peptide produced mainly in the liver and is the major physiological regulator of body iron stores and serum iron. It negatively regulates egress of iron from cells, such as intestinal epithelial cells and macrophages. Growth differentiation factor-15 (GDF-15) and twisted gastrulation protein homolog 1(TWSG1), two transforming growth factor-β (TGF-β) superfamily members released from erythroid precursors, have been proposed to contribute to hepcidin suppression in thalassemia, although it remains unresolved whether GDF-15 and TWSG1 are markers of ineffective erythropoiesis or mediators of hepcidin suppression in vivo.
With the presence of a thalassemia gene, patients with HbSβ-thalassemia (HbSβ0-thalassemia and HbSβ+-thalassemia) may have an increased tendency to absorb excess iron compared to patients with HbSS.
- Conditions
- Sickle Cell Anemia, Sickle - Beta Thalassemia
- Keywords
- sickle cell disease
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HbSS | Subjects are homozygous for the sickle hemoglobin mutation (HbS). | |
| HbS-beta thalassemia | Subjects are heterozygous for the HbS mutation and beta thalassemia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepcidin levels in HbSS and HbSβ-thalassemia SCD patients
Measured: Assessed at time of enrollment
Secondary outcomes (2)
Levels of GDF-15 in HbSS and HbSβ-thalassemia SCD patients
Measured: Assessed at time of enrollment
Ferritin and C-reactive protein (CRP) levels in SCD patients in the non-crisis state
Measured: Assessed at time of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2014 (estimated)
- Study startMar 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kenneth Ataga, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Augusta University
- Responsible party
- Sponsor-investigator, Kenneth Ataga, MD, University of North Carolina, Chapel Hill
- Investigators
- Kenneth I Ataga, MBBS, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02258997
- Sponsor's protocol ID
- 13-2811
- Status last verified
- Oct 2014
- First submitted
- 27 Sep 2014
- Last updated
- 8 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007 May;92(5):583-8. doi: 10.3324/haematol.10842.
PubMed 17488680Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A, Ladis V, Sakellaropoulos N, Papanikolaou G. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica. 2006 Jun;91(6):809-12.
PubMed 16769583Camberlein E, Zanninelli G, Detivaud L, Lizzi AR, Sorrentino F, Vacquer S, Troadec MB, Angelucci E, Abgueguen E, Loreal O, Cianciulli P, Lai ME, Brissot P. Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression. Haematologica. 2008 Jan;93(1):111-5. doi: 10.3324/haematol.11656.
PubMed 18166793Ezeh C, Ugochukwu CC, Weinstein J, Okpala I. Hepcidin, haemoglobin and ferritin levels in sickle cell anaemia. Eur J Haematol. 2005 Jan;74(1):86-8. doi: 10.1111/j.1600-0609.2004.00337.x. No abstract available.
PubMed 15613115
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepcidin Levels in Sickle Cell Disease (SCD)
- ClinicalTrials.gov ID
- NCT02258997
- Acronym / sponsor ID
- 13-2811
- Conditions
- Sickle Cell Anemia, Sickle - Beta Thalassemia
- Keywords
- sickle cell disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Kenneth Ataga, MDUniversity, hospital or other
- Collaborators
- Augusta University
- Study start
- Mar 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 8 Oct 2014 (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.
The investigators propose that patients with HbSβ-thalassemia have lower levels of hepcidin and higher levels of GDF-15 than HbSS patients during the non-crisis, "steady states." In addition, the investigators propose that when controlled for RBC transfusion, patients with HbSβ-thalassemia will have higher levels of storage iron (based on serum ferritin).
Participants: Total number of subjects is 42 - 21 subjects with HbSS, and 21 subjects with HbSβ-thalassemia ).
Procedures (methods): Eligible subjects with documented SCD (HbSS, HbS-β 0-thalassemia or HbS-β+-thalassemia) followed at the University of North Carolina (UNC) Comprehensive Sickle Cell Program will be evaluated in this single-center, prospective, cross-sectional study. The patients will be screened for eligibility at the time of a routine sickle cell clinic visit. Patients' data will be obtained in person at the time of evaluation and through review of their medical records. Investigators will obtain information on SCD-related clinical complications and obtain an estimate of the number of lifetime RBC transfusions. Blood samples will be obtained for laboratory tests. Plasma samples for hepcidin, growth differentiation factor 15 (GDF -15), and high-sensitivity CRP will be stored at -80 degrees Celsius until analysis. Other routine laboratory studies including complete blood count (CBC) with differential and reticulocyte count, serum iron profile and ferritin, and liver function tests will be performed at the clinical laboratories of UNC Hospitals.The subjects will have 30 ml. of blood drawn for this research study. Females of child bearing potential will have a urine pregnancy test at the time of the study.
Detailed description
Sickle cell disease (SCD) refers to a group of inherited disorders characterized by the presence of sickle hemoglobin (HbS) that are associated with episodes of acute illness and progressive organ damage. The most common variant of SCD, sickle cell anemia (HbSS), refers to homozygosity for the β S allele, with most of the remaining patients having sickle hemoglobin C disease (HbSC) and sickle beta thalassemia (HbSβ-thalassemia).
SCD may be associated with iron overload that occurs following repeated red blood cell (RBC) transfusions. However, in patients with beta thalassemia major, iron overload occurs due to both repeated RBC transfusions and hyperabsorption of iron. The hyperabsorption of iron in beta thalassemia occurs due to ineffective erythropoiesis and subsequent downregulation of hepcidin. Thalassemia intermedia and major are the most studied human models of hepcidin modulation by ineffective erythropoiesis alone and the combined and opposite effect of both ineffective erythropoiesis and transfusion dependent iron overload, accordingly. Regular transfusions induce massive iron loading but inhibit erythropoietic drive. Accordingly, hepcidin production is higher in thalassemia major than in thalassemia intermedia although still inappropriate to the massive transfusional iron loading that partially counteracts the erythropoietic-dependent hepcidin down-regulation (Origa R et al, 2007; Kattamis A et al, 2006; Camberlein E et al, 2008). No differences in the steady-state levels of hepcidin was observed when HbSS patients (N = 40) were compared with healthy hemoglobin AA (HbAA)controls (N = 30) (85.3 ± 30 l μg/L vs. 83.5 ± 40 l μg/L) (Ezeh C et al, 2005).
Hepcidin is a 25-amino acid peptide produced mainly in the liver and is the major physiological regulator of body iron stores and serum iron. It negatively regulates egress of iron from cells, such as intestinal epithelial cells and macrophages. Growth differentiation factor-15 (GDF-15) and twisted gastrulation protein homolog 1(TWSG1), two transforming growth factor-β (TGF-β) superfamily members released from erythroid precursors, have been proposed to contribute to hepcidin suppression in thalassemia, although it remains unresolved whether GDF-15 and TWSG1 are markers of ineffective erythropoiesis or mediators of hepcidin suppression in vivo.
With the presence of a thalassemia gene, patients with HbSβ-thalassemia (HbSβ0-thalassemia and HbSβ+-thalassemia) may have an increased tendency to absorb excess iron compared to patients with HbSS.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HbSS | – | –Subjects are homozygous for the sickle hemoglobin mutation (HbS). |
| HbS-beta thalassemia | – | –Subjects are heterozygous for the HbS mutation and beta thalassemia |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will be recruited from the population followed in the Adult Sickle Cell Clinic with either HbSS or HbS-βthalassemia who meet the eligibility criteria for the study.
Key inclusion criteria (5 listed)
- age 18 - 70 years
- confirmed diagnosis of HbSS or HbS-β thalassemia
- no history of acute vaso-occlusive event (acute pain crisis or acute chest syndrome) requiring emergency room visit or hospitalization over the preceding 4 weeks
- clinically acceptable physical examination and vital signs
- ability of patient or legal representative to understand the requirements of the study and willingness to sign the Informed Consent document.
Key exclusion criteria (6 listed)
- pregnancy or breastfeeding
- current acute illness, including a painful crisis
- iron deficiency anemia
- history of liver disease with alanine aminotransferase (ALT) ≥ 3 X upper limit of normal (ULN)
- history of hereditary hemochromatosis, connective tissues disease, chronic inflammatory, disorder, or malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hepcidin levels in HbSS and HbSβ-thalassemia SCD patients
Time frame: Assessed at time of enrollment
2 secondary outcomes
Levels of GDF-15 in HbSS and HbSβ-thalassemia SCD patients
Time frame: Assessed at time of enrollment
Ferritin and C-reactive protein (CRP) levels in SCD patients in the non-crisis state
Time frame: Assessed at time of enrollment
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 8 Oct 2015.
- Background: PubMed 17488680Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007 May;92(5):583-8. doi: 10.3324/haematol.10842.
- Background: PubMed 16769583Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A, Ladis V, Sakellaropoulos N, Papanikolaou G. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica. 2006 Jun;91(6):809-12.
- Background: PubMed 18166793Camberlein E, Zanninelli G, Detivaud L, Lizzi AR, Sorrentino F, Vacquer S, Troadec MB, Angelucci E, Abgueguen E, Loreal O, Cianciulli P, Lai ME, Brissot P. Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression. Haematologica. 2008 Jan;93(1):111-5. doi: 10.3324/haematol.11656.
- Background: PubMed 15613115Ezeh C, Ugochukwu CC, Weinstein J, Okpala I. Hepcidin, haemoglobin and ferritin levels in sickle cell anaemia. Eur J Haematol. 2005 Jan;74(1):86-8. doi: 10.1111/j.1600-0609.2004.00337.x. No abstract available.
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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.
Kenneth I Ataga, MBBS principal investigator
University of North Carolina, Chapel Hill
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Anemia and Sickle - Beta Thalassemia, run by Kenneth Ataga, MD.
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 5 inclusion and 6 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 8 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
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?
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?
Hepcidin levels in HbSS and HbSβ-thalassemia SCD patients (time frame: Assessed at time of enrollment). 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 NCT02258997, which also lists 4 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 8 Oct 2015.