Haemophilia and Bone Loss - PHILEOS Study

NCT04384341 | Recruiting

• 2 other identifiers: 19PH2242019-A03358-49
• Study Type: interventional
• Target: 480
• Locations: 5 countries
• Sites: 23

Brief Summary

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.

Conditions

Hemophilia

Keywords

Osteoporosis; fVIII; fIX; thrombin; Haemophilia; Hemophilia

Outcome Measures

Primary Outcomes (1)

• Osteoporosis defined by a T-score < -2.5 in severe haemophilic patients without prophylaxis and in healthy subjects.

  Bone mineral densitometry

  During the procedure

Secondary Outcomes (5)

• Osteoporosis defined by a T-score < -2.5 in the different groups of haemophilic patients and in in healthy subjects.

  During the procedure

• Osteopenia defined by a T-score < -1 in the different groups of haemophilic patients and in in healthy subjects.

  During the procedure

• Bone mineral density (expressed as a T-score) in the different groups of haemophilic patients and in healthy subjects.

  During the procedure

• Basal level of fVIII/fIX (expressed as an Ag level or as a %) or thrombin generation potential (expressed as an endogenous thrombin potential (ETP), nmol/min) and Bone mineral density (expressed as a T-score and Z-score)

  At the inclusion

• Markers influencing bone metabolism in all haemophilic patients included

  At the inclusion

Study Arms (2)

Haemophilic patients

EXPERIMENTAL

Blood sampling Bone Densitometry (BMD)

Radiation: Bone densitometry (BMD); Biological: Blood sampling for patients only

Healthy volunteers

OTHER

Bone Densitometry (BMD)

Radiation: Bone densitometry (BMD)

Interventions

Bone densitometry (BMD) 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.

Haemophilic patients; Healthy volunteers

Blood sampling for patients only BIOLOGICAL

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

Haemophilic patients

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Ministry of Health, France: collaborator

Study Sites (23)

BELGIUM - Brussels

Brussels, Belgium

RECRUITING

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

COMPLETED

Chu de Bordeaux

Bordeaux, 33076, France

RECRUITING

Chu Brest Hopital Morvan

Brest, 29200, France

RECRUITING

HCL - Groupement Hospitalier Est (Hôpital Louis Pradel)

Bron, France

RECRUITING

CHU Caen

Caen, France

RECRUITING

Centre Hospitalier Metropole Savoie

Chambéry, 73000, France

RECRUITING

Chu Cth Estaing Clermont Ferrand

Clermont-Ferrand, France

RECRUITING

Chu de Dijon

Dijon, 21000, France

RECRUITING

Chu Grenoble Alpes

Grenoble, 38700, France

RECRUITING

CHU Lille

Lille, France

RECRUITING

Chu La Timone Marseille

Marseille, 13010, France

RECRUITING

CHU - Saint Eloi

Montpellier, 34295, France

RECRUITING

CHU Nancy

Nancy, France

RECRUITING

CHU de Nantes

Nantes, France

RECRUITING

Chu Necker Paris

Paris, 75015, France

RECRUITING

APHP - Bicêtre

Paris, France

RECRUITING

Chu Rennes Hopital Pontchaillou

Rennes, 35000, France

RECRUITING

CHU de ROUEN

Rouen, France

RECRUITING

CHU de Saint-Etienne

Saint-Etienne, 42055, France

RECRUITING

Chu Strasbourg - Hôpital de Hautepierre

Strasbourg, France

RECRUITING

MHEK

Budapest, 1134, Hungary

COMPLETED

ROMANIA - Bucharest

Bucharest, Romania

RECRUITING

Related Publications (1)

• 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.

  PMID: 33441362 DERIVED

MeSH Terms

Conditions

Hemophilia A; Osteoporosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Brigitte TARDY, MD

  CHU de Saint Etienne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brigitte TARDY, MD

CONTACT

(0)477421877; brigitte.tardy@chu-st-etienne.fr

Carine LABRUYERE, CRA

CONTACT

(0)477120469; carine.labruyere@chu-st-etienne.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2020
• First Posted: May 12, 2020
• Study Start: June 2, 2020
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); FR (19); CR (1); HU (1); RO (1)