Haemophilia and Bone Loss - PHILEOS Study

NCT ID: NCT04384341

Last Updated: 2025-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

480 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-02

Study Completion Date

2025-03-31

Brief Summary

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Haemophilia is a rare bleeding disorder, characterized by factor VIII (HA) or factor IX (HB) deficiency. The absence or the reduction of fVIII or fIX result in impaired thrombin generation and clot formation, causing excessive bleeding (mainly haemarthrosis). Osteoporosis is a systemic bone disease characterized by a low bone mineral density (BMD). A decrease of mean BMD has been described in haemophilic patients compared to healthy controls in several studies. So, osteoporosis could be an underestimated haemophilia-related comorbidity. None of the following risk factors (reduced physical activity, joint damage, vitamin D deficiency and /or hepatitis C virus (HCV) infection) has been retained as a cause of osteoporosis in haemophilic patients. Another hypothesis is that bone loss could be directly linked to fVIII or fIX and/or thrombin deficiency. The aim of this study is to evaluate the prevalence of the bone loss in HA and B patients, according to the type, the severity and the presence (or not) of a prophylactic treatment (depending on the age at which it was began) and to compare it to a control population. The investigators will also evaluate the relation between BMD and FVIII, fIX and thrombin potential.

Detailed Description

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Recruitment of healthy volunteers through registers (Clinical Investigation Centers) and advertisements.

Recruitment of haemophilic patients during a routine visit at the haemophilia centre.

Information of the subjects that the study requires a BMD measure for all and a blood sampling for patients only.

After inclusion and exclusion criteria have been checked, the subject can sign the consent.

For all subjects, an appointment will be made for BMD measure. For patients and controls: BMD will be measured by Dual Energy X-ray Absorptiometry (DXA) technology, on femoral and lumbar spine (L2-L4) sites.

For patients, fVIII/fIX activity and antigen, thrombin generation potential and plasmatic markers of bone remodelling will be measured centrally.

Conditions

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Hemophilia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Haemophilic patients

Blood sampling Bone Densitometry (BMD)

Group Type EXPERIMENTAL

Bone densitometry (BMD)

Intervention Type RADIATION

Recruitment of haemophilic patients during a routine visit at the haemophilia centre.

Information of the subjects that the study requires a BMD measure for all and a blood sampling for patients only.

After inclusion and exclusion criteria have been checked, the subject can sign the consent.

For all subjects, an appointment will be made for BMD measure.

For patients and controls: BMD will be measured by Dual Energy X-ray Absorptiometry (DXA) technology, on femoral and lumbar spine (L2-L4) sites.

Recruitment of healthy volunteers through registers (Clinical Investigation Centers) and advertisements.

Blood sampling for patients only

Intervention Type BIOLOGICAL

For patients, fVIII/fIX activity and antigen, thrombin generation potential and plasmatic markers of bone remodelling will be measured centrally.

Healthy volunteers

Bone Densitometry (BMD)

Group Type OTHER

Bone densitometry (BMD)

Intervention Type RADIATION

Recruitment of haemophilic patients during a routine visit at the haemophilia centre.

Information of the subjects that the study requires a BMD measure for all and a blood sampling for patients only.

After inclusion and exclusion criteria have been checked, the subject can sign the consent.

For all subjects, an appointment will be made for BMD measure.

For patients and controls: BMD will be measured by Dual Energy X-ray Absorptiometry (DXA) technology, on femoral and lumbar spine (L2-L4) sites.

Recruitment of healthy volunteers through registers (Clinical Investigation Centers) and advertisements.

Interventions

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Bone densitometry (BMD)

Recruitment of haemophilic patients during a routine visit at the haemophilia centre.

Information of the subjects that the study requires a BMD measure for all and a blood sampling for patients only.

After inclusion and exclusion criteria have been checked, the subject can sign the consent.

For all subjects, an appointment will be made for BMD measure.

For patients and controls: BMD will be measured by Dual Energy X-ray Absorptiometry (DXA) technology, on femoral and lumbar spine (L2-L4) sites.

Recruitment of healthy volunteers through registers (Clinical Investigation Centers) and advertisements.

Intervention Type RADIATION

Blood sampling for patients only

For patients, fVIII/fIX activity and antigen, thrombin generation potential and plasmatic markers of bone remodelling will be measured centrally.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Healthy Volunteers :

* Healthy men aged between 20 to 60 years old
* Haemophilic Patients:

* Haemophilia A and B patients, irrespective of the disease form (mild, moderate, severe with or without prophylaxis)
* Haemophilic patients aged between 20 to 60 years old
* Severe Haemophilia A patients with prophylaxis : last factor VIII injection more than 48 to 120 hours (depending on on the prophylactic treatment) prior blood sampling dedicated to the this research
* Severe Haemophilia B patients : last factor IX injection more than 5 to 21 days (depending on the prophylactic treatment) prior blood sampling dedicated to the this research

Exclusion Criteria

* Healthy Volunteers:

* History of disease known to influence bone metabolism (hyperthyroidism, hyperparathyroidism, hypercorticism, hypogonadism, diseases that require long-term use of corticoids, …)
* Past or present treatment with any osteoporotic medication other than Vit D or Ca++
* Presence of two total hip prostheses
* HIV documented infection
* HCV documented infection (in progress or cured) at cirrhotic stage
* Haemophilic Patients:

* Haemophilic patients with current or history of inhibitor anti-fVIII or anti-fIX (\>5 Bethesda Units)
* Treatment with HEMLIBRA (Emicizumab). Unless it is possible to use a result of thrombin generation prior to this treatment and achieved with a residual rate not greater than or equal to 5%.
* History of disease known to influence bone metabolism and not related to haemophilia (hyperthyroidism, hyperparathyroidism, hypercorticism, hypogonadism, diseases that require long-term use of corticoids, …)
* Past or present treatment with any anti-osteoporotic medication other than Vit D or Ca++
* Presence of two total hip prostheses
* HIV documented infection
* HCV documented infection (in progress or cured) at cirrhotic stage
Minimum Eligible Age

20 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brigitte TARDY, MD

Role: PRINCIPAL_INVESTIGATOR

CHU de Saint Etienne

Locations

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BELGIUM - Brussels

Brussels, , Belgium

Site Status RECRUITING

University Hospital Centre Zagreb

Zagreb, , Croatia

Site Status COMPLETED

Chu de Bordeaux

Bordeaux, , France

Site Status RECRUITING

Chu Brest Hopital Morvan

Brest, , France

Site Status RECRUITING

HCL - Groupement Hospitalier Est (Hôpital Louis Pradel)

Bron, , France

Site Status RECRUITING

CHU Caen

Caen, , France

Site Status RECRUITING

Centre Hospitalier Metropole Savoie

Chambéry, , France

Site Status RECRUITING

Chu Cth Estaing Clermont Ferrand

Clermont-Ferrand, , France

Site Status RECRUITING

Chu de Dijon

Dijon, , France

Site Status RECRUITING

Chu Grenoble Alpes

Grenoble, , France

Site Status RECRUITING

CHU Lille

Lille, , France

Site Status RECRUITING

Chu La Timone Marseille

Marseille, , France

Site Status RECRUITING

CHU - Saint Eloi

Montpellier, , France

Site Status RECRUITING

CHU Nancy

Nancy, , France

Site Status RECRUITING

CHU de Nantes

Nantes, , France

Site Status RECRUITING

Chu Necker Paris

Paris, , France

Site Status RECRUITING

APHP - Bicêtre

Paris, , France

Site Status RECRUITING

Chu Rennes Hopital Pontchaillou

Rennes, , France

Site Status RECRUITING

CHU de ROUEN

Rouen, , France

Site Status RECRUITING

CHU de Saint-Etienne

Saint-Etienne, , France

Site Status RECRUITING

Chu Strasbourg - Hôpital de Hautepierre

Strasbourg, , France

Site Status RECRUITING

MHEK

Budapest, , Hungary

Site Status COMPLETED

ROMANIA - Bucharest

Bucharest, , Romania

Site Status RECRUITING

Countries

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Belgium Croatia France Hungary Romania

Central Contacts

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Brigitte TARDY, MD

Role: CONTACT

(0)477421877

Carine LABRUYERE, CRA

Role: CONTACT

(0)477120469

Facility Contacts

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Christine BIRON ANDREANI, MD

Role: primary

BRIGITTE TARDY

Role: primary

References

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Tardy-Poncet B, Play B, Montmartin A, Damien P, Ollier E, Presles E, Garcin A, Tardy B. PHILEOS (haemoPHILia and ostEoporOSis) Study: protocol of a multicentre prospective case-control study. BMJ Open. 2021 Jan 13;11(1):e042283. doi: 10.1136/bmjopen-2020-042283.

Reference Type DERIVED
PMID: 33441362 (View on PubMed)

Other Identifiers

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2019-A03358-49

Identifier Type: OTHER

Identifier Source: secondary_id

19PH224

Identifier Type: -

Identifier Source: org_study_id

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