Haemophilia and Bone Loss - PHILEOS Study

Hemophilia Clinical Trial

— PHILEOS  

Official title:

Haemophilia and Bone Loss PHILEOS Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04384341
• Other study ID #: 19PH224
• Secondary ID: 2019-A03358-49
• Status: Recruiting
• Phase: N/A
• Start date: June 2, 2020
• Est. completion date: March 2025

Study information

• Verified date: December 2023
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: Brigitte TARDY, MD
• Phone: (0)477421877
• Email: brigitte.tardy[@]chu-st-etienne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 480
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Radiation:
• 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.

Biological:
• 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.

Locations

Country	Name	City	State
Belgium	BELGIUM - Brussels	Brussel
France	Chu de Bordeaux	Bordeaux
France	Chu Brest Hopital Morvan	Brest
France	HCL - Groupement Hospitalier Est (Hôpital Louis Pradel)	Bron
France	CHU Caen	Caen
France	Centre Hospitalier Metropole Savoie	Chambéry
France	Chu Cth Estaing Clermont Ferrand	Clermont-Ferrand
France	Chu de Dijon	Dijon
France	Chu Grenoble Alpes	Grenoble
France	CHU Lille	Lille
France	Chu La Timone Marseille	Marseille
France	CHU - Saint Eloi	Montpellier
France	CHU Nancy	Nancy
France	CHU de Nantes	Nantes
France	APHP - Bicêtre	Paris
France	Chu Necker Paris	Paris
France	Chu Rennes Hopital Pontchaillou	Rennes
France	CHU de ROUEN	Rouen
France	CHU de Saint-Etienne	Saint-Étienne
France	Chu Strasbourg - Hôpital de Hautepierre	Strasbourg
Romania	ROMANIA - Bucharest	Bucharest

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Ministry of Health, France

Countries where clinical trial is conducted

Belgium,  France,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Osteoporosis defined by a T-score < -2.5 in the different groups of haemophilic patients and in in healthy subjects.	Bone mineral densitometry	During the procedure
Secondary	Osteopenia defined by a T-score < -1 in the different groups of haemophilic patients and in in healthy subjects.	Bone mineral densitometry	During the procedure
Secondary	Bone mineral density (expressed as a T-score) in the different groups of haemophilic patients and in healthy subjects.	Bone mineral densitometry	During the procedure
Secondary	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)	Blood test Relation between the basal level of fVIII or fIX (expressed as an Ag level or as a %) or the 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
Secondary	Markers influencing bone metabolism in all haemophilic patients included	Blood test	At the inclusion