Prospective Biomarkers of Bone Metabolism in Hemophilia A

NCT ID: NCT02306694

Last Updated: 2020-04-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2018-04-16

Brief Summary

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One of the major shortcomings in studying bone disease in hemophilia is the lack of fracture outcome data demonstrating the clinical significance of decreased BMD and altered bone biomarkers in the hemophilia population. This study demonstrates that PwH have an increased risk of fracture compared to the general population and that the issue of bone health will increase in importance as the PwH population ages.

Detailed Description

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This is a pilot study to determine the impact of factor replacement on bone biomarkers in up to 20 hemophilia A subjects. Subjects will be recruited over 1 year for the 5-day protocol.

Following a 72-hour washout period, factor levels and bone biomarkers will be followed before and after 50 units/kg replacement on Day 1 and 20 units/kg replacement on Day 3. Each subject can serve as their Figure 4. Fracture rates in PwH compared to historic controls.

Conditions

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Hemophilia Bone Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Open label

Everyone receives Advate (antihemophilic factor) on Day 1 and 3.

Group Type EXPERIMENTAL

Advate

Intervention Type DRUG

Patients who are currently taking Advate as their factor replacement will be eligible for the 5-day study.

Interventions

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Advate

Patients who are currently taking Advate as their factor replacement will be eligible for the 5-day study.

Intervention Type DRUG

Other Intervention Names

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Antihemophilic Factor (Recombinant)

Eligibility Criteria

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Inclusion Criteria

1. Males with a diagnosis of hemophilia A with a historic baseline FVIII level ≤ 2%.
2. Age \> 16 years old
3. Currently using ADVATE as FVIII replacement therapy

Exclusion Criteria

1. Subject or guardian is unwilling or unable to give written informed consent and/or assent
2. Joint or muscle bleeding within 2 weeks of Study Day 1
3. Presence of a current factor inhibitor (\>0.6 BU/mL via Nijmegan-modified Bethesda assay)
4. Known collagen vascular bone disease.
Minimum Eligible Age

16 Years

Maximum Eligible Age

85 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Baxter Healthcare Corporation

INDUSTRY

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jason Taylor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science

Locations

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Oregon Health and Science University

Portland, Oregon, United States

Site Status

Countries

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United States

References

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Plug I, Van Der Bom JG, Peters M, Mauser-Bunschoten EP, De Goede-Bolder A, Heijnen L, Smit C, Willemse J, Rosendaal FR. Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study. J Thromb Haemost. 2006 Mar;4(3):510-6. doi: 10.1111/j.1538-7836.2006.01808.x.

Reference Type BACKGROUND
PMID: 16460432 (View on PubMed)

Siboni SM, Mannucci PM, Gringeri A, Franchini M, Tagliaferri A, Ferretti M, Tradati FC, Santagostino E, von Mackensen S; Italian Association of Haemophilia Centres (AICE). Health status and quality of life of elderly persons with severe hemophilia born before the advent of modern replacement therapy. J Thromb Haemost. 2009 May;7(5):780-6. doi: 10.1111/j.1538-7836.2009.03318.x. Epub 2009 Feb 12.

Reference Type BACKGROUND
PMID: 19220727 (View on PubMed)

Gerstner G, Damiano ML, Tom A, Worman C, Schultz W, Recht M, Stopeck AT. Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia. Haemophilia. 2009 Mar;15(2):559-65. doi: 10.1111/j.1365-2516.2008.01963.x. Epub 2009 Feb 1.

Reference Type BACKGROUND
PMID: 19187193 (View on PubMed)

Wallny TA, Scholz DT, Oldenburg J, Nicolay C, Ezziddin S, Pennekamp PH, Stoffel-Wagner B, Kraft CN. Osteoporosis in haemophilia - an underestimated comorbidity? Haemophilia. 2007 Jan;13(1):79-84. doi: 10.1111/j.1365-2516.2006.01405.x.

Reference Type BACKGROUND
PMID: 17212729 (View on PubMed)

Barnes C, Wong P, Egan B, Speller T, Cameron F, Jones G, Ekert H, Monagle P. Reduced bone density among children with severe hemophilia. Pediatrics. 2004 Aug;114(2):e177-81. doi: 10.1542/peds.114.2.e177.

Reference Type BACKGROUND
PMID: 15286254 (View on PubMed)

Gallacher SJ, Deighan C, Wallace AM, Cowan RA, Fraser WD, Fenner JA, Lowe GD, Boyle IT. Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study. Q J Med. 1994 Mar;87(3):181-6.

Reference Type BACKGROUND
PMID: 8208906 (View on PubMed)

Tlacuilo-Parra A, Morales-Zambrano R, Tostado-Rabago N, Esparza-Flores MA, Lopez-Guido B, Orozco-Alcala J. Inactivity is a risk factor for low bone mineral density among haemophilic children. Br J Haematol. 2008 Mar;140(5):562-7. doi: 10.1111/j.1365-2141.2007.06972.x.

Reference Type BACKGROUND
PMID: 18275434 (View on PubMed)

Amorosa V, Tebas P. Bone disease and HIV infection. Clin Infect Dis. 2006 Jan 1;42(1):108-14. doi: 10.1086/498511. Epub 2005 Nov 30.

Reference Type BACKGROUND
PMID: 16323100 (View on PubMed)

Anagnostis P, Vakalopoulou S, Vyzantiadis TA, Charizopoulou M, Karras S, Goulis DG, Karagiannis A, Gerou S, Garipidou V. The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B. Haemophilia. 2014 Mar;20(2):268-75. doi: 10.1111/hae.12271. Epub 2013 Oct 7.

Reference Type BACKGROUND
PMID: 24118364 (View on PubMed)

Liel MS, Greenberg DL, Recht M, Vanek C, Klein RF, Taylor JA. Decreased bone density and bone strength in a mouse model of severe factor VIII deficiency. Br J Haematol. 2012 Jul;158(1):140-3. doi: 10.1111/j.1365-2141.2012.09101.x. Epub 2012 Apr 2. No abstract available.

Reference Type BACKGROUND
PMID: 22469061 (View on PubMed)

Kempton CL, Antun A, Antoniucci DM, Carpenter W, Ribeiro M, Stein S, Slovensky L, Elon L. Bone density in haemophilia: a single institutional cross-sectional study. Haemophilia. 2014 Jan;20(1):121-8. doi: 10.1111/hae.12240. Epub 2013 Aug 1.

Reference Type BACKGROUND
PMID: 23902277 (View on PubMed)

Lee SK, Lorenzo J. Cytokines regulating osteoclast formation and function. Curr Opin Rheumatol. 2006 Jul;18(4):411-8. doi: 10.1097/01.bor.0000231911.42666.78.

Reference Type BACKGROUND
PMID: 16763463 (View on PubMed)

Brinker MR, O'Connor DP. The incidence of fractures and dislocations referred for orthopaedic services in a capitated population. J Bone Joint Surg Am. 2004 Feb;86(2):290-7.

Reference Type BACKGROUND
PMID: 14960673 (View on PubMed)

Roche AF, Roberts J, Hamill PV. Skeletal maturity of youths 12--17 years racial, geographic area, and socioeconomic differentials. United States, 1966-1970. Vital Health Stat 11. 1978 Oct;(167):1-98. No abstract available.

Reference Type BACKGROUND
PMID: 214960 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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e11104

Identifier Type: -

Identifier Source: org_study_id

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