Vascular Function, Sarcopenia and Pain in Postmenopausal Osteoporosis

NCT ID: NCT05228262

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-15
• Study Completion Date: 2027-02-01

Brief Summary

This study aims to follow a cohort of osteoporotic patients treated with anti-osteoporotic drugs and to evaluate the impact of these treatments on the osteoporosis-cardiovascular-sarcopenia triad and on pain.

Detailed Description

Exploratory study involving functional explorations in longitudinal follow-up, initiated in parallel with a treatment indicated in the patient's usual care and management.

The main objective is the evaluation of the evolution of the vascular and endothelial function.

The secondary objectives are:

1. To study the evolution of cardiovascular parameters,

2. To study the evolution of sarcopenia,

3. To study the evolution of quality of life and pain,

4. To study the evolution of bone remodeling (by creating a collection of biological samples),

5. To study the genetic predisposition of osteoporosis including the confirmation of known genetic markers and the potential identification of new genetic variants involved (by creating a biobank),

6. To study epigenetic biomarkers in the osteoporosis patient population (by creating a biobank),

7. To study the role of the microbiota in osteoporosis patients (by creating a biobank),

8. To study the determinants of the evolution of the studied parameters and to identify trajectories (therapeutic response profiles).

As part of their usual care and management, patients will be diagnosed with osteoporosis and prescribed anti-osteoporotic drugs.

The patients will have six visits: a pre-selection visit that will take place in the Rheumatology Department of the Clermont-Ferrand University Hospital and five visits that will take place in the Clinical Investigation Platform/Clinical Investigation Center (PIC/CIC) Inserm 1405 of the Clermont-Ferrand University Hospital.

Visit 0 - Screening visit and diagnosis of osteoporosis T0-1: Rheumatology Department

During this visit, the investigator physician will perform various examinations and tests usually performed as part of the patient's usual care and management in order to establish a diagnosis of osteoporosis.

These examinations are as follows:

• Bone densitometry less than one year old using Dual energy X-ray Absorptiometry (DXA),
• Bone biological assessment, including the following tests: Complete Blood Count (CBC), platelets, C-Reactive Protein (CRP), urea, creatinine with CKD-EPI clearance calculation, liver enzymes (AST, ALT), serum calcium, serum calcium corrected by albumin, serum phosphorus, serum protein electrophoresis, Thyroid Stimulating Hormone (TSH), 25 OH vitamin D, serum CTX (C-terminal telopeptides of type 1 collagen).

Some patients who require profile radiographs of the spine will have this examination added for the consultation, especially for the evaluation of vertebral fractures if the context justifies it. Other patients will also have these x-rays for the calculation of the abdominal aortic calcification score (Kauppila score) by the rheumatologist.

Body composition will be requested during the bone densitometry evaluation on the DXA machine.

Once the diagnosis of osteoporosis is confirmed, the physician will propose to the eligible patients to participate in this research protocol by explaining the objectives and the course of the study, and give them an information note in order to give them a necessary time of reflection of a maximum of one month, depending on the scheduling of the inclusion visit.

If patients are interested,the investigator physician will prescribe osteoporotic treatment to be started after the V1 (T0) inclusion visit.

Visit 1 - Inclusion visit - T0: PIC/CIC (2 hours)

During this visit, the physician will explain again the objectives and progress of the study with the different tests and questionnaires planned so that the patients can give their informed consent to participate.

During this visit, the following will be performed:

• A medical examination,
• A blood sample in order to obtain a collection of biological samples for the purpose of:

1. Assess bone biomarkers (osteocalcin, sclerostin, periostin, irisin, N-terminal propeptide of procollagen type 1 (P1NP), Dickkopf-related protein 1 (DKK1) and C-terminal telopeptides of collagen type 1 (CTX)),

2. Characterize genetic predispositions to osteoporosis,

3. Characterize epigenetic biomarkers in the osteoporosis patient population by microRNA analysis,

• Stool sampling to obtain a biobank for subsequent microbiota analysis,
• Cardiovascular exploration based on the measurement of the increase in the diameter of the brachial artery (FMD, "Flow-Mediated Dilation"); measurement of the increase in digital volume (RHI, "Reactive Hyperhemia Index") and measurement of the microcirculatory perfusion of the skin at the level of the hand (FLD, "Flow Laser Doppler"), and measurement of the stiffness of the main arteries (aorta) by the technique of Pulse Wave Velocity (PWV) measurement,
• Exploration of sarcopenia: the following questionnaires and tests will be performed: SARC-F (Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls) and SPPB (Short Physical Performance Battery),
• Quality of life component questionnaires: Pittsburgh Sleep Quality Index (PSQI), 36-Item Short Form Survey (SF-36), Numerical Pain Scale (NPS), Bref Pain Inventory (BPI), and Hospital Anxiety and Depression scale (HADs).

Visit 2 (T0+1 year) and Visit 4 (T0+3 years): PIC/CIC (1h15)

During this visit, the following examinations, tests and questionnaires will be performed:

• A physical examination,
• A blood and stool sample to obtain a collection of biological samples (bone biomarkers, microRNA and microbiota analyses),
• A cardiovascular exploration with FMD, RHI, FLD and PWV measurements,
• Exploration of sarcopenia: questionnaires and tests SARC-F, SPPB and measurement of muscle function will be performed,
• Quality of life component questionnaires: Pittsburgh Sleep Quality Index (PSQI), SF-36 quality of life questionnaire, Numerical Pain Scale (NPS), Bref Pain Inventory (BPI), and Hospital Anxiety and Depression scale (HADs).

Visit 3 (T0+2 years) and visit 5 (T0+4 years): PIC/CIC (1h30)

During this visit, the following examinations, tests and questionnaires will be performed:

• A physical examination,
• A blood and stool sample to obtain a collection of biological samples (bone biomarkers, microRNA and microbiota analyses),
• A cardiovascular exploration with FMD, RHI, FLD and PWV measurements,
• Exploration of sarcopenia: questionnaires and tests SARC-F, SPPB, measurement of muscle function and DXA with body composition measurement will be performed,
• Quality of life component questionnaires: Pittsburgh Sleep Quality Index (PSQI), SF-36 quality of life questionnaire, Numerical Pain Scale (NPS), Bref Pain Inventory (BPI), and Hospital Anxiety and Depression scale (HADs).

Visit 5 will be the last visit of the study.

Conditions

Osteoporosis, Postmenopausal

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cohort follow-up

Exploratory study involving functional explorations in longitudinal follow-up, initiated in parallel with a treatment indicated in the patient's usual care and management.

Group Type: OTHER

Cohort follow-up

Intervention Type: OTHER

• Inclusion medical consultation,
• Inclusion clinical examination,
• Collection of biological samples (bone biomarkers, epigenetic biomarkers (microRNA)) and analysis of microbiota and genotyping,
• Calculation of the Kauppila score on profile spine radiographs by the rheumatologist,
• Cardiovascular investigations (FMD, "Flow-Mediated Dilation"); measurement of digital volume increase (RHI, "Reactive hyperhemia index"); measurement of microcirculatory perfusion of the skin at the hand (FLD, "Flow Laser Doppler") ; measurement of the stiffness of the main arteries (aorta) by the Pulse Wave Velocity (PWV),
• Exploration of sarcopenia: questionnaires and tests: SARC-F, SPPB, muscle strength,
• Quality of life component questionnaires Pittsburgh Sleep (PSQI), Numerical Scale (NS), Brief Pain Inventory (BPI), Hospital Anxiety and Depression scale (HADs), and 36-Item Short Form Survey (SF-36) Quality of Life Questionnaire.

Interventions

Cohort follow-up

• Inclusion medical consultation,
• Inclusion clinical examination,
• Collection of biological samples (bone biomarkers, epigenetic biomarkers (microRNA)) and analysis of microbiota and genotyping,
• Calculation of the Kauppila score on profile spine radiographs by the rheumatologist,
• Cardiovascular investigations (FMD, "Flow-Mediated Dilation"); measurement of digital volume increase (RHI, "Reactive hyperhemia index"); measurement of microcirculatory perfusion of the skin at the hand (FLD, "Flow Laser Doppler") ; measurement of the stiffness of the main arteries (aorta) by the Pulse Wave Velocity (PWV),
• Exploration of sarcopenia: questionnaires and tests: SARC-F, SPPB, muscle strength,
• Quality of life component questionnaires Pittsburgh Sleep (PSQI), Numerical Scale (NS), Brief Pain Inventory (BPI), Hospital Anxiety and Depression scale (HADs), and 36-Item Short Form Survey (SF-36) Quality of Life Questionnaire.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Women aged 50 years or older with postmenopausal osteoporosis, whether fractured or not, requiring initiation of treatment with antiosteoporotic drugs (bisphosphonates, raloxifene, teriparatide, denosumab and others to come for this indication, including romosozumab), either orally or by injection, as part of their care and management.
• Able to give informed consent to participate in research.
• Affiliation to a Social Security system.

Exclusion Criteria

• Patient with chronic renal failure, defined as glomerular filtration rate < 30 mL.min-1 estimated by CKD-EPI.
• Patient with a medical and/or surgical history deemed by the investigator or his/her representative to be incompatible with the trial.
• Patient under legal protection or deprived of liberty.
• Refusal to participate.

• Minimum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie-Eva Pickering

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Locations

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Lise LACLAUTRE

Role: CONTACT

promo_interne_drci@chu-clermontferrand.fr

+33473754963

Facility Contacts

Lise Laclautre

Role: primary

promo_interne_drci@chu-clermontferrand.fr

+33473754963

Other Identifiers

2021-A02276-35

Identifier Type: OTHER

Identifier Source: secondary_id

RBHP 2021 ME_PICKERING

Identifier Type: -

Identifier Source: org_study_id