Sickle Cells DiseaseNCT02972138
Vitamin D and Bisphosphonates in the Treatment of Sickle Cell Disease
An observational study of Sickle Cells Disease, run by Società Italiana Talassemie ed Emoglobinopatie at 3 sites in Italy.
Trial summary
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75,000 individuals in the United States and almost 20,000- 25,000 subjects in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharian Africa to European countries. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Sickle Cells Disease
- How many people
- 80 participants
- Where
- 3 sitesItaly
- Study dates
- Jan 2010to Sep 2017
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Study population: Patients with sickle cell disease older than 18 years of age and younger than 50 years of age
Who may be able to join
- Young adult patients with sickle cell disease (older than 18 years of age) and younger than 50 years of age
Who cannot join
- Women with positive pregnant test, patients with history of heart, renal and liver failure, patients taking drugs influencing bone metabolisms within the two years before the beginning of the study (i.e.: glucocorticoids, hormonal replacement)
- Patients in meonopause, patients with traumatic vertebral fracture
- Patients with hypo/hyperthyroidism
- Patients with hyperparathyroidism
- Patients with osteomalacia, patients with history of Paget disease
- Patients with Cushing syndrome
- Patients with malabsorption diseases (i.e.: caeliac disease)
- Patients with history of cancer
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Ospedali Galliera - S.S.D. Microcitemia, anemie congenite e dismetabolismo del ferro
Genova, 16128
Ospedali Galliera - S.S.D. Ortogeriatria per intensità di cure
Genova, 16128
Università degli Studi di Verona
Verona, 37129
About this study
Official title: Vitamin D Supplementation and Anti-resorptive Therapy (Bisphosphonates) Treatment of Young Adult Patients With Sickle Cell Disease
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75,000 individuals in the United States and almost 20,000- 25,000 subjects in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharian Africa to European countries. Studies of global burden disease have pointed out the invalidating impact of SCD on patient quality of life. This requires the development of new therapeutic options to treat sickle cell related acute and chronic complications. SCD is caused by a point mutation in the β-globin gene resulting in the synthesis of pathological hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density and further acceleration of HbS polymerization. Pathophysiological studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of SCD, in which intravascular sickling in capillaries and small vessels leads to vaso-occlusion and impaired blood flow with ischemic/reperfusion injury. In microcirculation, vaso-occlusive events (VOC) result from a complex and still partially known scenario, involving the interactions between different cell types, including dense red cells, reticulocytes, abnormally activated endothelial cells, leukocytes, platelets and plasma factors. Target organs, such as bone or lung, are involved in both acute and chronic clinical manifestations of SCD, related to their peculiar anatomic organization mainly characterized by sluggish circulation and relative local hypoxia. VOCs combined with marrow hyperplasia and inflammation has been suggested to contribute to the development of sickle bone disease (SBD). Recently, it has been proposed a possible role of vitamin D deficiency in SBD, which appears to be subordinated to the primary defect in bone homeostasis. In a humanized mouse model for SCD, we recently reported that SBD is due to imbalance between osteoblast/osteoclast activity induced by recurrent VOCs. In addition, we show that zoledronic acid prevents bone impairment related to SCD, reducing osteoclast activity and improving osteoblast performance.
Read the detailed description
This is a retrospective study aimed to evaluate sickle bone disease (SBD) in a population of young adult patients with sickle cell disease treated with vitamin D supplementation and anti-resorptive therapy (bisphosphonates). We plan to analyze data from 1 January 2010 to 31 December 2015.
In addition to the standard hematological analysis, the following parameters and radiologic exams will be evaluated:
- Serum levels of Ca2+, P, Vitamin D, parathormone , creatinine, blood urea nitrogen , Na, K, Cl
- Bone turnover markers: C-terminal telopeptide (CTX), N-terminal propeptide of type I procollagen (PINP)
- Bone densitometry (DXA) at lumbar spine and proximal femur
- Standard X-Ray at dorsal-lumbar spine in LL projection for morphometric analysis
- Conditions
- Sickle Cells Disease
- Keywords
- Sickle-cells Disease, bisphosphonates, Vitamine D
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of vertebral fracture
Measured: 5 years follow up
Secondary outcomes (2)
severity of vertebral fracture
Measured: 5 years follow up
Incidence of non-vertebral fracture
Measured: 5 years follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2016 (estimated)
- Study startJan 2010
- Primary completionDec 2015
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Sickle Cells DiseaseStudies 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
- Retrospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Società Italiana Talassemie ed Emoglobinopatie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luca G Dalle Carbonare, MD, Principal investigator, Università degli studi di Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02972138
- Sponsor's protocol ID
- Vit.D-Bisph-SCD
- Status last verified
- Dec 2015
- First submitted
- 28 Oct 2016
- Last updated
- 6 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7. doi: 10.2471/blt.06.036673.
PubMed 18568278Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79(8):704-12. Epub 2001 Oct 24.
PubMed 11545326De Franceschi L, Cappellini MD, Olivieri O. Thrombosis and sickle cell disease. Semin Thromb Hemost. 2011 Apr;37(3):226-36. doi: 10.1055/s-0031-1273087. Epub 2011 Mar 31.
PubMed 21455857Eaton WA, Hofrichter J. Sickle cell hemoglobin polymerization. Adv Protein Chem. 1990;40:63-279. doi: 10.1016/s0065-3233(08)60287-9. No abstract available.
PubMed 2195851De Franceschi L, Corrocher R. Established and experimental treatments for sickle cell disease. Haematologica. 2004 Mar;89(3):348-56.
PubMed 15020275Ballas SK, Smith ED. Red blood cell changes during the evolution of the sickle cell painful crisis. Blood. 1992 Apr 15;79(8):2154-63.
PubMed 1562742Vinchi F, De Franceschi L, Ghigo A, Townes T, Cimino J, Silengo L, Hirsch E, Altruda F, Tolosano E. Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases. Circulation. 2013 Mar 26;127(12):1317-29. doi: 10.1161/CIRCULATIONAHA.112.130179. Epub 2013 Feb 27.
PubMed 23446829Hebbel RP, Vercellotti G, Nath KA. A systems biology consideration of the vasculopathy of sickle cell anemia: the need for multi-modality chemo-prophylaxsis. Cardiovasc Hematol Disord Drug Targets. 2009 Dec;9(4):271-92. doi: 10.2174/1871529x10909040271.
PubMed 19751187Hebbel RP. Adhesion of sickle red cells to endothelium: myths and future directions. Transfus Clin Biol. 2008 Feb-Mar;15(1-2):14-8. doi: 10.1016/j.tracli.2008.03.011. Epub 2008 May 23.
PubMed 18501652Platt OS. The acute chest syndrome of sickle cell disease. N Engl J Med. 2000 Jun 22;342(25):1904-7. doi: 10.1056/NEJM200006223422510. No abstract available.
PubMed 10861328Lal A, Fung EB, Pakbaz Z, Hackney-Stephens E, Vichinsky EP. Bone mineral density in children with sickle cell anemia. Pediatr Blood Cancer. 2006 Dec;47(7):901-6. doi: 10.1002/pbc.20681.
PubMed 16317761Dalle Carbonare L, Innamorati G, Valenti MT. Transcription factor Runx2 and its application to bone tissue engineering. Stem Cell Rev Rep. 2012 Sep;8(3):891-7. doi: 10.1007/s12015-011-9337-4.
PubMed 22139789Bruzzaniti A, Baron R. Molecular regulation of osteoclast activity. Rev Endocr Metab Disord. 2006 Jun;7(1-2):123-39. doi: 10.1007/s11154-006-9009-x.
PubMed 16951988Dalle Carbonare L, Zanatta M, Gasparetto A, Valenti MT. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management. Drug Healthc Patient Saf. 2010;2:121-37. doi: 10.2147/DHPS.S6285. Epub 2010 Aug 19.
PubMed 21701624Dalle Carbonare L, Arlot ME, Chavassieux PM, Roux JP, Portero NR, Meunier PJ. Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res. 2001 Jan;16(1):97-103. doi: 10.1359/jbmr.2001.16.1.97.
PubMed 11149495
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
- Vitamin D Supplementation and Anti-resorptive Therapy (Bisphosphonates) Treatment of Young Adult Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT02972138
- Acronym / sponsor ID
- Vit.D-Bisph-SCD
- Conditions
- Sickle Cells Disease
- Keywords
- Sickle-cells Disease, bisphosphonates, Vitamine D
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Società Italiana Talassemie ed EmoglobinopatieUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 23 Nov 2016 (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.
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, which affects approximately 75,000 individuals in the United States and almost 20,000- 25,000 subjects in Europe, this latter mainly related to the immigration fluxes from endemic areas such as Sub-Saharian Africa to European countries. Studies of global burden disease have pointed out the invalidating impact of SCD on patient quality of life. This requires the development of new therapeutic options to treat sickle cell related acute and chronic complications. SCD is caused by a point mutation in the β-globin gene resulting in the synthesis of pathological hemoglobin S (HbS). HbS displays peculiar biochemical characteristics, polymerizing when deoxygenated with associated reduction in cell ion and water content (cell dehydration), increased red cell density and further acceleration of HbS polymerization. Pathophysiological studies have shown that dense, dehydrated red cells play a central role in acute and chronic clinical manifestations of SCD, in which intravascular sickling in capillaries and small vessels leads to vaso-occlusion and impaired blood flow with ischemic/reperfusion injury. In microcirculation, vaso-occlusive events (VOC) result from a complex and still partially known scenario, involving the interactions between different cell types, including dense red cells, reticulocytes, abnormally activated endothelial cells, leukocytes, platelets and plasma factors. Target organs, such as bone or lung, are involved in both acute and chronic clinical manifestations of SCD, related to their peculiar anatomic organization mainly characterized by sluggish circulation and relative local hypoxia. VOCs combined with marrow hyperplasia and inflammation has been suggested to contribute to the development of sickle bone disease (SBD). Recently, it has been proposed a possible role of vitamin D deficiency in SBD, which appears to be subordinated to the primary defect in bone homeostasis. In a humanized mouse model for SCD, we recently reported that SBD is due to imbalance between osteoblast/osteoclast activity induced by recurrent VOCs. In addition, we show that zoledronic acid prevents bone impairment related to SCD, reducing osteoclast activity and improving osteoblast performance.
Detailed description
This is a retrospective study aimed to evaluate sickle bone disease (SBD) in a population of young adult patients with sickle cell disease treated with vitamin D supplementation and anti-resorptive therapy (bisphosphonates). We plan to analyze data from 1 January 2010 to 31 December 2015.
In addition to the standard hematological analysis, the following parameters and radiologic exams will be evaluated:
- Serum levels of Ca2+, P, Vitamin D, parathormone , creatinine, blood urea nitrogen , Na, K, Cl
- Bone turnover markers: C-terminal telopeptide (CTX), N-terminal propeptide of type I procollagen (PINP)
- Bone densitometry (DXA) at lumbar spine and proximal femur
- Standard X-Ray at dorsal-lumbar spine in LL projection for morphometric analysis
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Patients with sickle cell disease older than 18 years of age and younger than 50 years of age
Key inclusion criteria (1 listed)
- Young adult patients with sickle cell disease (older than 18 years of age) and younger than 50 years of age
Key exclusion criteria (8 listed)
- Women with positive pregnant test, patients with history of heart, renal and liver failure, patients taking drugs influencing bone metabolisms within the two years before the beginning of the study (i.e.: glucocorticoids, hormonal replacement)
- Patients in meonopause, patients with traumatic vertebral fracture
- Patients with hypo/hyperthyroidism
- Patients with hyperparathyroidism
- Patients with osteomalacia, patients with history of Paget disease
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
Incidence of vertebral fracture
Time frame: 5 years follow up
2 secondary outcomes
severity of vertebral fracture
Time frame: 5 years follow up
Incidence of non-vertebral fracture
Time frame: 5 years follow up
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 18568278Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7. doi: 10.2471/blt.06.036673.
- Background: PubMed 11545326Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79(8):704-12. Epub 2001 Oct 24.
- Background: PubMed 21455857De Franceschi L, Cappellini MD, Olivieri O. Thrombosis and sickle cell disease. Semin Thromb Hemost. 2011 Apr;37(3):226-36. doi: 10.1055/s-0031-1273087. Epub 2011 Mar 31.
- Background: PubMed 2195851Eaton WA, Hofrichter J. Sickle cell hemoglobin polymerization. Adv Protein Chem. 1990;40:63-279. doi: 10.1016/s0065-3233(08)60287-9. No abstract available.
- Background: PubMed 15020275De Franceschi L, Corrocher R. Established and experimental treatments for sickle cell disease. Haematologica. 2004 Mar;89(3):348-56.
- Background: PubMed 1562742Ballas SK, Smith ED. Red blood cell changes during the evolution of the sickle cell painful crisis. Blood. 1992 Apr 15;79(8):2154-63.
- Background: PubMed 23446829Vinchi F, De Franceschi L, Ghigo A, Townes T, Cimino J, Silengo L, Hirsch E, Altruda F, Tolosano E. Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases. Circulation. 2013 Mar 26;127(12):1317-29. doi: 10.1161/CIRCULATIONAHA.112.130179. Epub 2013 Feb 27.
- Background: PubMed 19751187Hebbel RP, Vercellotti G, Nath KA. A systems biology consideration of the vasculopathy of sickle cell anemia: the need for multi-modality chemo-prophylaxsis. Cardiovasc Hematol Disord Drug Targets. 2009 Dec;9(4):271-92. doi: 10.2174/1871529x10909040271.
- Background: PubMed 18501652Hebbel RP. Adhesion of sickle red cells to endothelium: myths and future directions. Transfus Clin Biol. 2008 Feb-Mar;15(1-2):14-8. doi: 10.1016/j.tracli.2008.03.011. Epub 2008 May 23.
- Background: PubMed 10861328Platt OS. The acute chest syndrome of sickle cell disease. N Engl J Med. 2000 Jun 22;342(25):1904-7. doi: 10.1056/NEJM200006223422510. No abstract available.
- Background: PubMed 16317761Lal A, Fung EB, Pakbaz Z, Hackney-Stephens E, Vichinsky EP. Bone mineral density in children with sickle cell anemia. Pediatr Blood Cancer. 2006 Dec;47(7):901-6. doi: 10.1002/pbc.20681.
- Background: PubMed 22139789Dalle Carbonare L, Innamorati G, Valenti MT. Transcription factor Runx2 and its application to bone tissue engineering. Stem Cell Rev Rep. 2012 Sep;8(3):891-7. doi: 10.1007/s12015-011-9337-4.
- Individual participant dataSharing planned: Undecided
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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.
Luca G Dalle Carbonare, MD principal investigator
Università degli studi di Verona
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cells Disease, run by Società Italiana Talassemie ed Emoglobinopatie at 3 sites in Italy.
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 1 inclusion and 8 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 3 sites in Italy. 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?
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?
Incidence of vertebral fracture (time frame: 5 years follow up). 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 NCT02972138, which also lists 19 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.