Prospective Biomarkers of Bone Metabolism in Hemophilia A

March 23, 2020 updated by: Oregon Health and Science University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 85 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Open label
Everyone receives Advate (antihemophilic factor) on Day 1 and 3.
Drug: Advate
Patients who are currently taking Advate as their factor replacement will be eligible for the 5-day study.
Other Names:
  • Antihemophilic Factor (Recombinant)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Biomarker Density (BMD)
Time Frame: 5 days
BMD was measured as Z-scores/T-scores using Dual-Energy X-ray Absorptiometry (DEXA) scanning; specifically looking at Spine, Hip/Neck, and Hip total scores. BMD Z-scores compare what would be expected in someone your age and body size. A Z-score, is a unit of standard deviation, where above 0 would indicate the bones are more dense than expected, while a Z-score below 0 would indicate the bones were less dense.
5 days
Joint Health
Time Frame: 5 days
Hemophilia Joint Health Score (HJHS); with a higher score representing worst outcomes, scores could range from 0 (no problems) to a max score of 120 (severe problems).
5 days
Quality of Life Using the VAS and EQ-5D-3L
Time Frame: 5 days
Visual Analog Scale (VAS) via the EQ-5D-3L was used to report participants self-rated health. EQ-5D-3L total score ranges from 5 (no problems) to 15 (significant problems). VAS scores could range from 0 (worst health ever) to 100 (best health ever).
5 days
Plasma Cytokine Concentration Differences From 0-hour to 24-hour
Time Frame: 24 hours
cytokines were measured using ELISA/magnetic bead multiplex kits. We calculated concentration change from hour 0 to hour 24. Cytokines: FGF, C-Terminal telopeptide (CTX-1), Dickkopf WNT signaling pathway inhibitor 1(DKK1), Eotaxin, fibroblast growth factor 23(FGF23), interferon gamma, interleukin 13, interleukin 1 beta, interleukin receptor 1 antagonist, interleukin 2, interleukin 4, interleukin 6, interleukin 17, interleukin 8, interleukin 9 Insulin, interferon gamma induced protein 10 (IP10), Leptin, monocyte chemoattractant protein1, monocyte chemoattractant protein1, macrophage inflammatory protein 1a (MIP1a), osteoclasts, Osteoprotegerin, osteopontin, platelet derived growth factors, parathyroid horomone, Recepter activator of nuclear factor kappa-B ligand (RANKL), chemokine ligand 5, sclerostin, transforming growth factor-beta 1, transforming growth factor beta 2, transforming growth factor beta 3, tumor necrosis factor alpha, vascular endothelial growth factor, MIP1b.
24 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Medication Adherence
Time Frame: 5 days
VERITAS instrument self-reported compliance with factor replacement regimen. The VERITAS is composed of 6 subsections, where scores range from 1 (best adherence) to 5 (worst adherence). A total score was calculated with the minimum score of 24 (most adherent) and a maximum score of 120 (least adherent)
5 days
Hemophilia Activities List (HAL) and the International Society of Thrombosis and Hemostasis- Bleeding Assessment Tool (ISTH-BAT)
Time Frame: 5 days
The HAL is used to assess physical activity; scores range from 42 (severe problems) to 252 (no problems). The ISTH-BAT was used to evaluate bleeding phenotype. Each section was scored using a 0 to 4 scale for each of the 12 subsections. A total score was calculated by taking the sum of each section, resulting in a range of scores from 0 (no bleeding history) to 48 (most extensive clinical intervention for bleeding)
5 days
Participant Quality of Life
Time Frame: 5 days
Haem-A-QoL was used to assess various components indicating participants quality of life. Haem-A-QoL is composed of 10 subsections with 3-8 questions in each. Questions are rated from 1 to 5, with 5 being the most negative influence on quality of life. Some questions are worded in the inverse, such that the 1 corresponds to the greatest negative impact on quality of life. In this case, the score is inverted to match the remainder of questions for statistical analysis. A Transformed scores is calculated for each subsection and for the total of all the subjections. The scores range from 0 (best quality of life) to 225 (worst quality of life).
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oregon Health and Science University

Collaborators

Baxter Healthcare Corporation

Investigators

  • Principal Investigator: Jason Taylor, MD, PhD, Oregon Health and Science

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2014

Primary Completion (ACTUAL)

April 16, 2018

Study Completion (ACTUAL)

April 16, 2018

Study Registration Dates

First Submitted

November 25, 2014

First Submitted That Met QC Criteria

December 1, 2014

First Posted (ESTIMATE)

December 3, 2014

Study Record Updates

Last Update Posted (ACTUAL)

April 1, 2020

Last Update Submitted That Met QC Criteria

March 23, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • e11104

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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