Clinical trial NCT05228262: Vascular Function, Sarcopenia and Pain in Postmenopausal Osteoporosis
Official title: Study on Vascular Function, Sarcopenia and Pain in Treated Postmenopausal Osteoporosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteoporosis, Postmenopausal
Keywords: Osteoporosis
Sarcopenia
Cardiovascular
FMD
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2022-02-08
Enrollment: 150
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Population of postmenopausal women ≥50 years of age with osteoporosis requiring the initiation of antiosteoporotic therapy.
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Endothelial dysfunction measured by FMD (Flow-Mediated Dilation) in patients with anti-osteoporotic treatment
timeFrame: Visit 1: Day 0
measure: Endothelial dysfunction measured by FMD (Flow-Mediated Dilation) in patients with anti-osteoporotic treatment
timeFrame: Visit 2: Day 0+1 year
measure: Endothelial dysfunction measured by FMD (Flow-Mediated Dilation) in patients with anti-osteoporotic treatment
timeFrame: Visit 3: Day 0+2 years
measure: Endothelial dysfunction measured by FMD (Flow-Mediated Dilation) in patients with anti-osteoporotic treatment
timeFrame: Visit 4: Day 0+3 years
measure: Endothelial dysfunction measured by FMD (Flow-Mediated Dilation) in patients with anti-osteoporotic treatment
timeFrame: Visit 5: Day 0+4 years
Secondary outcomes:
measure: Measurement of digital volume increase by RHI (Reactive hyperhemia index), (Endo-PAT2000; Itamar Medical Ltd, Israel).
timeFrame: Visit 1: Day 0
measure: Measurement of digital volume increase by RHI (Reactive hyperhemia index), (Endo-PAT2000; Itamar Medical Ltd, Israel).
timeFrame: Visit 2: Day 0+1 year
measure: Measurement of digital volume increase by RHI (Reactive hyperhemia index), (Endo-PAT2000; Itamar Medical Ltd, Israel).
timeFrame: Visit 3: Day 0+2 years
measure: Measurement of digital volume increase by RHI (Reactive hyperhemia index), (Endo-PAT2000; Itamar Medical Ltd, Israel).
timeFrame: Visit 4: Day 0+3 years
measure: Measurement of digital volume increase by RHI (Reactive hyperhemia index), (Endo-PAT2000; Itamar Medical Ltd, Israel).
timeFrame: Visit 5: Day 0+4 years
measure: Microcirculation measurement by FLD (Flow Laser Doppler), PeriFlux® (Perimed)
timeFrame: Visit 1: Day 0
measure: Microcirculation measurement by FLD (Flow Laser Doppler), PeriFlux® (Perimed)
timeFrame: Visit 2: Day 0+1 year
measure: Microcirculation measurement by FLD (Flow Laser Doppler), PeriFlux® (Perimed)
timeFrame: Visit 3: Day 0+2 years
measure: Microcirculation measurement by FLD (Flow Laser Doppler), PeriFlux® (Perimed)
timeFrame: Visit 4: Day 0+3 years
measure: Microcirculation measurement by FLD (Flow Laser Doppler), PeriFlux® (Perimed)
timeFrame: Visit 5: Day 0+4 years
measure: Sphygmocor CPV® (Atcor Medical) large artery stiffness measurement (PWV)
timeFrame: Visit 1: Day 0
measure: Sphygmocor CPV® (Atcor Medical) large artery stiffness measurement (PWV)
timeFrame: Visit 2: Day 0+1 year
measure: Sphygmocor CPV® (Atcor Medical) large artery stiffness measurement (PWV)
timeFrame: Visit 3: Day 0+2 years
measure: Sphygmocor CPV® (Atcor Medical) large artery stiffness measurement (PWV)
timeFrame: Visit 4: Day 0+3 years
measure: Sphygmocor CPV® (Atcor Medical) large artery stiffness measurement (PWV)
timeFrame: Visit 5: Day 0+4 years
measure: Evaluation of the Abdominal Aorta Calcification (AAC) (Kauppila score)
timeFrame: Preselection visit V0: Day 0-1 month (D0-1)
measure: Evaluation of the Abdominal Aorta Calcification (AAC) (Kauppila score)
timeFrame: Visit 5: Day 0+4 years
measure: Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) questionnaire
timeFrame: Visit 1: Day 0
measure: Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) questionnaire
timeFrame: Visit 2: Day 0+1 year
measure: Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) questionnaire
timeFrame: Visit 3: Day 0+2 years
measure: Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) questionnaire
timeFrame: Visit 4: Day 0+3 years
measure: Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) questionnaire
timeFrame: Visit 5: Day 0+4 years
measure: Short Physical Performance Battery (SPPB) Questionnaire
timeFrame: Visit 1: Day 0
measure: SPPB Questionnaire
timeFrame: Visit 2: Day 0+1 year
measure: SPPB Questionnaire
timeFrame: Visit 3: Day 0+2 years
measure: SPPB Questionnaire
timeFrame: Visit 4: Day 0+3 years
measure: SPPB Questionnaire
timeFrame: Visit 5: Day 0+4 years
measure: Evaluation of the muscular strength
timeFrame: Visit 1: Day 0
measure: Evaluation of the muscular strength
timeFrame: Visit 2: Day 0+1 year
measure: Evaluation of the muscular strength
timeFrame: Visit 3: Day 0+2 years
measure: Evaluation of the muscular strength
timeFrame: Visit 4: Day 0+3 years
measure: Evaluation of the muscular strength
timeFrame: Visit 5: Day 0+4 years
measure: Body composition measurement on Dual energy X-ray Absorptiometry (DXA)
timeFrame: Preselection visit V0: Day 0-1 month (D0-1)
measure: Body composition measurement on Dual energy X-ray Absorptiometry (DXA)
timeFrame: Visit 3: Day 0+2 years
measure: Body composition measurement on Dual energy X-ray Absorptiometry (DXA)
timeFrame: Visit 5: Day 0+4 years
measure: The Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Visit 1: Day 0
measure: The Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Visit 2: Day 0+1 year
measure: The Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Visit 3: Day 0+2 years
measure: The Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Visit 4: Day 0+3 years
measure: The Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Visit 5: Day 0+4 years
measure: The Brief Pain Inventory Questionnaire (BPI)
timeFrame: Visit 1: Day 0
measure: The Brief Pain Inventory Questionnaire (BPI)
timeFrame: Visit 2: Day 0+1 year
measure: The Brief Pain Inventory Questionnaire (BPI)
timeFrame: Visit 3: Day 0+2 years
measure: The Brief Pain Inventory Questionnaire (BPI)
timeFrame: Visit 4: Day 0+3 years
measure: The Brief Pain Inventory Questionnaire (BPI)
timeFrame: Visit 5: Day 0+4 years
measure: The numerical pain scale
timeFrame: Visit 1: Day 0
measure: The numerical pain scale
timeFrame: Visit 2: Day 0+1 year
measure: The numerical pain scale
timeFrame: Visit 3: Day 0+2 years
measure: The numerical pain scale
timeFrame: Visit 4: Day 0+3 years
measure: The numerical pain scale
timeFrame: Visit 5: Day 0+4 years
measure: The Hospital Anxiety and Depression Scale (HAD)
timeFrame: Visit 1: Day 0
measure: The Hospital Anxiety and Depression Scale (HAD)
timeFrame: Visit 2: Day 0+1 year
measure: The Hospital Anxiety and Depression Scale (HAD)
timeFrame: Visit 3: Day 0+2 years
measure: The Hospital Anxiety and Depression Scale (HAD)
timeFrame: Visit 4: Day 0+3 years
measure: The Hospital Anxiety and Depression Scale (HAD)
timeFrame: Visit 5: Day 0+4 years
measure: The 36-Item Short Form Survey (SF-36)
timeFrame: Visit 1: Day 0
measure: The 36-Item Short Form Survey (SF-36)
timeFrame: Visit 2: Day 0+1 year
measure: The 36-Item Short Form Survey (SF-36)
timeFrame: Visit 3: Day 0+2 years
measure: The 36-Item Short Form Survey (SF-36)
timeFrame: Visit 4: Day 0+3 years
measure: The 36-Item Short Form Survey (SF-36)
timeFrame: Visit 5: Day 0+4 years
measure: Sclerostin dosage
timeFrame: Visit 1: Day 0
measure: Sclerostin dosage
timeFrame: Visit 2: Day 0+1 year
measure: Sclerostin dosage
timeFrame: Visit 3: Day 0+2 years
measure: Sclerostin dosage
timeFrame: Visit 4: Day 0+3 years
measure: Sclerostin dosage
timeFrame: Visit 5: Day 0+4 years
measure: Osteocalcin dosage
timeFrame: Visit 1: Day 0
measure: Osteocalcin dosage
timeFrame: Visit 2: Day 0+1 year
measure: Osteocalcin dosage
timeFrame: Visit 3: Day 0+2 years
measure: Osteocalcin dosage
timeFrame: Visit 4: Day 0+3 years
measure: Osteocalcin dosage
timeFrame: Visit 5: Day 0+4 years
measure: Periostin dosage
timeFrame: Visit 1: Day 0
measure: Periostin dosage
timeFrame: Visit 2: Day 0+1 year
measure: Periostin dosage
timeFrame: Visit 3: Day 0+2 years
measure: Periostin dosage
timeFrame: Visit 4: Day 0+3 years
measure: Periostin dosage
timeFrame: Visit 5: Day 0+4 years
measure: Irisin dosage
timeFrame: Visit 1: Day 0
measure: Irisin dosage
timeFrame: Visit 2: Day 0+1 year
measure: Irisin dosage
timeFrame: Visit 3: Day 0+2 years
measure: Irisin dosage
timeFrame: Visit 4: Day 0+3 years
measure: Irisin dosage
timeFrame: Visit 5: Day 0+4 years
measure: N-terminal propeptide of procollagen type 1 (P1NP) dosage
timeFrame: Visit 1: Day 0
measure: N-terminal propeptide of procollagen type 1 (P1NP) dosage
timeFrame: Visit 2: Day 0+1 year
measure: N-terminal propeptide of procollagen type 1 (P1NP) dosage
timeFrame: Visit 3: Day 0+2 years
measure: N-terminal propeptide of procollagen type 1 (P1NP) dosage
timeFrame: Visit 4: Day 0+3 years
measure: N-terminal propeptide of procollagen type 1 (P1NP) dosage
timeFrame: Visit 5: Day 0+4 years
measure: Dickkopf-related protein 1 (DKK1) dosage
timeFrame: Visit 1: Day 0
measure: Dickkopf-related protein 1 (DKK1) dosage
timeFrame: Visit 2: Day 0+1 year
measure: Dickkopf-related protein 1 (DKK1) dosage
timeFrame: Visit 3: Day 0+2 years
measure: Dickkopf-related protein 1 (DKK1) dosage
timeFrame: Visit 4: Day 0+3 years
measure: Dickkopf-related protein 1 (DKK1) dosage
timeFrame: Visit 5: Day 0+4 years
measure: C-terminal telopeptides of collagen type 1 (CTX) dosage
timeFrame: Visit 1: Day 0
measure: C-terminal telopeptides of collagen type 1 (CTX) dosage
timeFrame: Visit 2: Day 0+1 year
measure: C-terminal telopeptides of collagen type 1 (CTX) dosage
timeFrame: Visit 3: Day 0+2 years
measure: C-terminal telopeptides of collagen type 1 (CTX) dosage
timeFrame: Visit 4: Day 0+3 years
measure: C-terminal telopeptides of collagen type 1 (CTX) dosage
timeFrame: Visit 5: Day 0+4 years
measure: Distribution of gene polymorphisms using OpenArray technology
timeFrame: Visit 1: Day 0
measure: MicroRNA analysis using OpenArray technology
timeFrame: Visit 1: Day 0
measure: MicroRNA analysis using OpenArray technology
timeFrame: Visit 2: Day 0+1 year
measure: MicroRNA analysis using OpenArray technology
timeFrame: Visit 3: Day 0+2 years
measure: MicroRNA analysis using OpenArray technology
timeFrame: Visit 4: Day 0+3 years
measure: MicroRNA analysis using OpenArray technology
timeFrame: Visit 5: Day 0+4 years
measure: Study of the microbiota
timeFrame: Visit 1: Day 0
measure: Study of the microbiota
timeFrame: Visit 2: Day 0+1 year
measure: Study of the microbiota
timeFrame: Visit 3: Day 0+2 years
measure: Study of the microbiota
timeFrame: Visit 4: Day 0+3 years
measure: Study of the microbiota
timeFrame: Visit 5: Day 0+4 years
measure: Identification of predictive factors of treatment effectiveness according to variations in vascular and endothelial function parameters and pain, which will be studied first as quantitative parameters and then as categorical data.
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Marie-Eva Pickering
role: PRINCIPAL_INVESTIGATOR
References: