Back to resultsHaemophilia and Bone Loss - PHILEOS Study (PHILEOS)
Primary Purpose
Hemophilia
Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Bone densitometry (BMD)
Blood sampling for patients only
Sponsored by
About this trial
This is an interventional screening trial for Hemophilia focused on measuring Osteoporosis, fVIII, fIX, thrombin, Haemophilia, Hemophilia
Eligibility Criteria
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
Sites / Locations
- BELGIUM - BrusselsRecruiting
- Chu de BordeauxRecruiting
- Chu Brest Hopital MorvanRecruiting
- HCL - Groupement Hospitalier Est (Hôpital Louis Pradel)Recruiting
- CHU CaenRecruiting
- Centre Hospitalier Metropole SavoieRecruiting
- Chu Cth Estaing Clermont FerrandRecruiting
- Chu de DijonRecruiting
- Chu Grenoble AlpesRecruiting
- CHU LilleRecruiting
- Chu La Timone MarseilleRecruiting
- CHU - Saint EloiRecruiting
- CHU NancyRecruiting
- CHU de NantesRecruiting
- Chu Necker ParisRecruiting
- APHP - BicêtreRecruiting
- Chu Rennes Hopital PontchaillouRecruiting
- CHU de ROUENRecruiting
- CHU de Saint-EtienneRecruiting
- Chu Strasbourg - Hôpital de HautepierreRecruiting
- ROMANIA - BucharestRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Haemophilic patients
Healthy volunteers
Arm Description
Blood sampling Bone Densitometry (BMD)
Bone Densitometry (BMD)
Outcomes
Primary Outcome Measures
Osteoporosis defined by a T-score < -2.5 in severe haemophilic patients without prophylaxis and in healthy subjects.
Bone mineral densitometry
Secondary Outcome Measures
Osteoporosis defined by a T-score < -2.5 in the different groups of haemophilic patients and in in healthy subjects.
Bone mineral densitometry
Osteopenia defined by a T-score < -1 in the different groups of haemophilic patients and in in healthy subjects.
Bone mineral densitometry
Bone mineral density (expressed as a T-score) in the different groups of haemophilic patients and in healthy subjects.
Bone mineral densitometry
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)
Markers influencing bone metabolism in all haemophilic patients included
Blood test
Full Information
NCT ID
NCT04384341
First Posted
May 5, 2020
Last Updated
June 6, 2023
Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Ministry of Health, France
1. Study Identification
Unique Protocol Identification Number
NCT04384341
Brief Title
Haemophilia and Bone Loss - PHILEOS Study
Acronym
PHILEOS
Official Title
Haemophilia and Bone Loss PHILEOS Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 2, 2020 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Ministry of Health, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia
Keywords
Osteoporosis, fVIII, fIX, thrombin, Haemophilia, Hemophilia
7. Study Design
Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
480 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Haemophilic patients
Arm Type
Experimental
Arm Description
Blood sampling Bone Densitometry (BMD)
Arm Title
Healthy volunteers
Arm Type
Other
Arm Description
Bone Densitometry (BMD)
Intervention Type
Radiation
Intervention Name(s)
Bone densitometry (BMD)
Intervention Description
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
Biological
Intervention Name(s)
Blood sampling for patients only
Intervention Description
For patients, fVIII/fIX activity and antigen, thrombin generation potential and plasmatic markers of bone remodelling will be measured centrally.
Primary Outcome Measure Information:
Title
Osteoporosis defined by a T-score < -2.5 in severe haemophilic patients without prophylaxis and in healthy subjects.
Description
Bone mineral densitometry
Time Frame
During the procedure
Secondary Outcome Measure Information:
Title
Osteoporosis defined by a T-score < -2.5 in the different groups of haemophilic patients and in in healthy subjects.
Description
Bone mineral densitometry
Time Frame
During the procedure
Title
Osteopenia defined by a T-score < -1 in the different groups of haemophilic patients and in in healthy subjects.
Description
Bone mineral densitometry
Time Frame
During the procedure
Title
Bone mineral density (expressed as a T-score) in the different groups of haemophilic patients and in healthy subjects.
Description
Bone mineral densitometry
Time Frame
During the procedure
Title
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)
Description
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)
Time Frame
At the inclusion
Title
Markers influencing bone metabolism in all haemophilic patients included
Description
Blood test
Time Frame
At the inclusion
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brigitte TARDY, MD
Phone
(0)477421877
Email
brigitte.tardy@chu-st-etienne.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Carine LABRUYERE, CRA
Phone
(0)477120469
Email
carine.labruyere@chu-st-etienne.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte TARDY, MD
Organizational Affiliation
CHU de Saint Etienne
Official's Role
Principal Investigator
Facility Information:
Facility Name
BELGIUM - Brussels
City
Brussel
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cedric HERMANS, MD
Facility Name
Chu de Bordeaux
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SABINE CASTET, MD
First Name & Middle Initial & Last Name & Degree
Nadia MESHEN-CETRE, MD
Facility Name
Chu Brest Hopital Morvan
City
Brest
ZIP/Postal Code
29200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BRIGITTE PAN-PETESCH, MD
Facility Name
HCL - Groupement Hospitalier Est (Hôpital Louis Pradel)
City
Bron
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne LIENHART, MD
Facility Name
CHU Caen
City
Caen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yohann REPESSE, MD
First Name & Middle Initial & Last Name & Degree
Philippe GAUTIER, MD
First Name & Middle Initial & Last Name & Degree
Benjamin GILLET, MD
Facility Name
Centre Hospitalier Metropole Savoie
City
Chambéry
ZIP/Postal Code
73000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ROMAIN JAILLER, MD
First Name & Middle Initial & Last Name & Degree
VALERIE GAY, MD
First Name & Middle Initial & Last Name & Degree
Pascal MEYER, MD
Facility Name
Chu Cth Estaing Clermont Ferrand
City
Clermont-Ferrand
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
AURELIEN LEBRETON, MD
First Name & Middle Initial & Last Name & Degree
Victoria CACHEUX, MD
First Name & Middle Initial & Last Name & Degree
Alain MARQUES-VERDIER, MD
Facility Name
Chu de Dijon
City
Dijon
ZIP/Postal Code
21000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
FABIENNE GENRE-VOLLOT, MD
First Name & Middle Initial & Last Name & Degree
Marc BARDOU, MD-PhD
First Name & Middle Initial & Last Name & Degree
Maxime LUU, MD
First Name & Middle Initial & Last Name & Degree
Inès BEN GHEZALA, MD
Facility Name
Chu Grenoble Alpes
City
Grenoble
ZIP/Postal Code
38700
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
RAPHAEL MARLU, MD
First Name & Middle Initial & Last Name & Degree
BENOIT POLACK, MD
First Name & Middle Initial & Last Name & Degree
Enkelejda HODAJ, MD
Facility Name
CHU Lille
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine RAUCH, MD
First Name & Middle Initial & Last Name & Degree
Sophie SUSEN, MD PhD
First Name & Middle Initial & Last Name & Degree
Bénédicte WIBAUT-PEGNEAUX, MD
First Name & Middle Initial & Last Name & Degree
Isabelle MENDEL, MD
Facility Name
Chu La Timone Marseille
City
Marseille
ZIP/Postal Code
13010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CELINE FALAISE, MD
First Name & Middle Initial & Last Name & Degree
HERVE CHAMBOST, MD PhD
First Name & Middle Initial & Last Name & Degree
Catherine POUYMAYOU, MD
First Name & Middle Initial & Last Name & Degree
Pierre Emmanuel MORANGE, MD PhD
Facility Name
CHU - Saint Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine BIRON ANDREANI, MD
First Name & Middle Initial & Last Name & Degree
Christine BIRON ANDREANI, MD
First Name & Middle Initial & Last Name & Degree
Delphine CHIFFRE-RAKOTOARIVONY, MD
First Name & Middle Initial & Last Name & Degree
Robert NAVARRO, MD
Facility Name
CHU Nancy
City
Nancy
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birgit FROTSCHER
Facility Name
CHU de Nantes
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc FOUASSIER, MD
Facility Name
Chu Necker Paris
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
LAURENT FRENZEL, MD
Facility Name
APHP - Bicêtre
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roseline D'OIRON, MD
First Name & Middle Initial & Last Name & Degree
Hortense MAYNADIE, MD
First Name & Middle Initial & Last Name & Degree
Guillaume MORELLE, MD
Facility Name
Chu Rennes Hopital Pontchaillou
City
Rennes
ZIP/Postal Code
35000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BENOIT GUILLET, MD
First Name & Middle Initial & Last Name & Degree
Fabrice LAINE, MD
First Name & Middle Initial & Last Name & Degree
Elodie MAINGUY, MD
First Name & Middle Initial & Last Name & Degree
Marie PROVOST-DEWITTE, MD
Facility Name
CHU de ROUEN
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PIERRE CHAMOUNI, MD
First Name & Middle Initial & Last Name & Degree
Virginie BARBAY, MD
First Name & Middle Initial & Last Name & Degree
Marie KOZYREFF-MEURICE, MD
Facility Name
CHU de Saint-Etienne
City
Saint-Étienne
ZIP/Postal Code
42055
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BRIGITTE TARDY
First Name & Middle Initial & Last Name & Degree
THIERRY THOMAS, MD-PhD
First Name & Middle Initial & Last Name & Degree
BRIGITTE TARDY, MD
First Name & Middle Initial & Last Name & Degree
Anne DEVILLARD, MD
First Name & Middle Initial & Last Name & Degree
Bernard TARDY, MD-PhD
Facility Name
Chu Strasbourg - Hôpital de Hautepierre
City
Strasbourg
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DOMINIQUE DESPREZ, MD
First Name & Middle Initial & Last Name & Degree
Rose-Marie JAVIER, MD
Facility Name
ROMANIA - Bucharest
City
Bucharest
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel CORIU, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33441362
Citation
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.
Results Reference
derived
Learn more about this trial
Haemophilia and Bone Loss - PHILEOS Study
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