MAGnesium Effect With ANtiosteoporotic Drugs

NCT ID: NCT05328154

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-28
• Study Completion Date: 2024-12-19

Brief Summary

Randomized pilot clinical trial to demonstrate superiority of bisphosphonate-magnesium combination over bisphosphonates alone in postmenopausal osteoporosis in slowing bone remodeling as assessed by C-terminal telopeptide of bone collagen type 1 (CTX) dosage.

Detailed Description

A pilot, randomized, controlled, open-label, single-center, two-parallel-arm clinical trial testing the addition of oral magnesium supplementation to prescribed drug therapy in the care setting. Category 1.

The primary objective of this randomized trial is to demonstrate the superiority of the combination of bisphosphonates and magnesium over bisphosphonates alone in postmenopausal osteoporosis, in terms of slowing bone remodeling, as assessed by the measurement of C-terminal telopeptides of type 1 bone collagen (CTX).

The secondary objectives are to study the impact of magnesium supplementation at 1 year on:

1. the evolution of other biological markers of bone remodeling (by creating a collection of biological samples) and bone densitometry on the following sites: spine, femoral neck, total femur,

2. the evolution of cardiovascular parameters,

3. the follow-up of the incidence of fractures,

4. the evolution of sarcopenia,

5. the evolution of quality of life and pain,

6. 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),

7. the epigenetic biomarkers in the osteoporosis patient population (by creating a biobank),

8. the role of the microbiota in osteoporosis patients (by creating a biobank),

9. the occurrence of adverse events.

As part of their usual care and management, patients will be diagnosed with osteoporosis and prescribed bisphosphonates.

Patients will have 3 or 4 visits depending on which group they are randomized to: a first screening visit as part of routine care, which will take place in the Rheumatology Department of the Clermont-Ferrand University Hospital, then 2 visits for patients in the "bisphosphonates alone" group and 3 visits for patients in the "bisphosphonates associated with magnesium" group, which will take place in the Inserm 1405 Clinical Investigation Platform/Clinical Investigation Center (PIC/CIC) of the Clermont-Ferrand University Hospital.

Visit 0 - Screening visit and diagnosis of osteoporosis (1 month before day 0): 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 follow:

• Bone densitometry less than one year using Dual X-ray Absorptiometry (DXA), either previously performed by the patient or prescribed at this consultation.
• 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.

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 to calculate the abdominal aortic calcification score (Kauppila score).

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 eligible patients to participate in this research protocol by explaining the objectives and the course of the study, and give them an information note.

If the patients are interested, the investigator physician will prescribe osteoporotic treatment to be started after the Visit 1: Day 0 inclusion visit.

Visit 1 - Inclusion visit (Day 0): 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 to measure magnesium levels and to obtain a collection of biological samples in order to:

1. Evaluate bone biomarkers (osteocalcin, sclerostin, periostin, irisin, N-terminal propeptide of procollagen type 1 (P1NP), Dickkopf-related protein 1 (DKK1)),

2. Characterize genetic predispositions of osteoporosis,

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

• A stool sample to obtain a biobank for subsequent microbiota analysis.
• A 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 Hyperemia 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 stars, and Falls), SPPB (Short Physical Performance Battery), the measurement of the muscular function and DXA with the measurement of the body composition.
• Pain exploration: Numerical Pain Scale (NPS), Brief Pain Inventory (BPI), and pain thresholds.
• Quality of life component questionnaires: Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADs) and the 36-Item Short Form Survey (SF-36).
• Randomization into two groups: a "bisphosphonates associated with magnesium" group, and a "bisphosphonates alone" group.
• Delivery of a daily follow-up diary to evaluate the average pain per day, the consumption of analgesics, and the occurrence of any adverse effects.

For the "bisphosphonates alone" group, this diary will be completed for the first month of taking bisphosphonates (Month 1) as well as for the last month before the end of study visit at one year (Month 12).

For the "bisphosphonates combined with magnesium" group, a diary will also be given to them for the first month of taking bisphosphonates and a second will be given to them at visit 2 which will cover the period of taking magnesium over the last 3 months preceding the end-of-study visit (Months 10 to 12).

Visit 2 only for patients in the bisphosphonate-magnesium arm (Day 0+9 months): PIC/CIC (15 minutes)

At this visit, 9 months after the start of the trial, a blood test will be performed to measure magnesium levels, and then patients will be given magnesium treatment to take daily for 3 months before their 1-year visit (during months 10, 11 and 12). Finally, they will be given a follow-up diary to evaluate the average pain per Numerical Pain Scale, the daily consumption of analgesics, and the occurrence of possible adverse effects.

→ In addition, for the patients in this group, a phone call will be made by the project team 6 weeks after the start of the magnesium treatment to ensure good tolerance and compliance with the magnesium intake.

Visit 3 - End of study visit at 1 year (Day 0+1 year): PIC/CIC (1h15)

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

• A medical examination,
• A blood sample to measure magnesium levels, serum CTX and other biological bone markers (osteocalcin, sclerostin, periostin, irisin, P1NP, DKK1) and to perform microRNA analysis by collecting biological samples,
• A stool sample to study the microbiota (constitution of a collection of biological samples),
• A bone densitometry measurement (DXA),
• A cardiovascular exploration with FMD, RHI, FLD and PWV measurements and an estimation of the Kauppila score.
• Exploration of sarcopenia: questionnaires and tests SARC-F, SPPB, measurement of muscle function and body composition.
• Exploration of pain: NPS, BPI, and pain thresholds.
• Quality of life component questionnaires: PSQI, HADs and the SF-36. As part of routine care, patients will then be seen in a follow-up rheumatology consultation to confirm the indication for continuing treatment with biphosphonates, with a blood test identical to that performed during the pre-selection visit.

Visit 3 will be the last visit of the study.

Conditions

Osteoporosis, Postmenopausal

Keywords

Osteoporosis; Magnesium; CTX; Bone remodeling

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bisphosphonates (zoledronic acid, Aclasta® 5 mg) alone

Bisphosphonates are considered as the gold standard of treatment for osteoporosis. Zoledronic acid, Aclasta® 5 mg will be administered intravenously according to standard management criteria in order to obtain an homogeneous population.

Group Type: OTHER

Follow-up of patients with postmenopausal osteoporosis, with or without fractures, requiring initiation of injectable bisphosphonate therapy as part of their usual care

Intervention Type: OTHER

• Inclusion medical consultation
• Inclusion clinical examination
• Calculation of Kauppila score at one year
• Imaging procedures (DXA) at 1 year
• Magnesium dosage: Visit 1: Day 0 and Visit 3: Day 0+1 year
• Samples for biological collection and microbiota analysis Visit 1: Day 0 and Visit 3: Day 0+1 year
• Genotyping in Visit 1: Day 0
• Serum CTX dosage in Visit 3: Day 0+1 year
• Cardiovascular investigations (FMD, RHI, FLD, PWV) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of sarcopenia (SARC-F, SPPB, muscle strength and body composition) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of pain (NPS, BPI, sensitivity/pain thresholds, CPM) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Quality of life component questionnaires (PSQI, HADs, SF-36) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Follow-up diary to be completed at months 1 and 12 of the study

bisphosphonates (zoledronic acid, Aclasta® 5 mg) associated with magnesium (MAG 2®, 100 mg)

In addition to bisphosphonates, patients in this group will take a 3-month treatment of magnesium (magnesium carbonate, MAG 2® 100 mg), 2 tablets of 100 mg/day, during the 3 months preceding the 1-year visit.

Group Type: ACTIVE_COMPARATOR

Follow-up of patients with postmenopausal osteoporosis, fractured or not, requiring initiation of injectable bisphosphonate therapy as part of care with magnesium supplementation

Intervention Type: DRUG

• Inclusion medical consultation
• Inclusion clinical examination
• Calculation of Kauppila score at one year
• Imaging procedures (DXA) at 1 year
• Magnesium dosage: Visit 1: Day 0; Visit 2: Day 0+9 months and Visit 3: Day 0+1 year
• Samples for biological collection and microbiota analysis Visit 1: Day 0 and Visit 3: Day 0+1 year
• Genotyping in Visit 1: Day 0
• Serum CTX dosage in Visit 3: Day 0+1 year
• Cardiovascular investigations (FMD, RHI, FLD, PWV) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of sarcopenia (SARC-F, SPPB, muscle strength and body composition) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of pain (NPS, BPI, sensitivity/pain thresholds, CPM) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Quality of life component questionnaires (PSQI, HADs, SF-36) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Magnesium intake for 1 period of 3 months
• Phone call
• Follow-up diary to be completed at months 1, 10, 11 and 12 of the study

Interventions

Follow-up of patients with postmenopausal osteoporosis, with or without fractures, requiring initiation of injectable bisphosphonate therapy as part of their usual care

• Inclusion medical consultation
• Inclusion clinical examination
• Calculation of Kauppila score at one year
• Imaging procedures (DXA) at 1 year
• Magnesium dosage: Visit 1: Day 0 and Visit 3: Day 0+1 year
• Samples for biological collection and microbiota analysis Visit 1: Day 0 and Visit 3: Day 0+1 year
• Genotyping in Visit 1: Day 0
• Serum CTX dosage in Visit 3: Day 0+1 year
• Cardiovascular investigations (FMD, RHI, FLD, PWV) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of sarcopenia (SARC-F, SPPB, muscle strength and body composition) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of pain (NPS, BPI, sensitivity/pain thresholds, CPM) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Quality of life component questionnaires (PSQI, HADs, SF-36) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Follow-up diary to be completed at months 1 and 12 of the study

Intervention Type: OTHER

Follow-up of patients with postmenopausal osteoporosis, fractured or not, requiring initiation of injectable bisphosphonate therapy as part of care with magnesium supplementation

• Inclusion medical consultation
• Inclusion clinical examination
• Calculation of Kauppila score at one year
• Imaging procedures (DXA) at 1 year
• Magnesium dosage: Visit 1: Day 0; Visit 2: Day 0+9 months and Visit 3: Day 0+1 year
• Samples for biological collection and microbiota analysis Visit 1: Day 0 and Visit 3: Day 0+1 year
• Genotyping in Visit 1: Day 0
• Serum CTX dosage in Visit 3: Day 0+1 year
• Cardiovascular investigations (FMD, RHI, FLD, PWV) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of sarcopenia (SARC-F, SPPB, muscle strength and body composition) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Exploration of pain (NPS, BPI, sensitivity/pain thresholds, CPM) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Quality of life component questionnaires (PSQI, HADs, SF-36) in Visit 1: Day 0 and Visit 3: Day 0+1 year
• Magnesium intake for 1 period of 3 months
• Phone call
• Follow-up diary to be completed at months 1, 10, 11 and 12 of the study

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women aged 50 years or older, with postmenopausal osteoporosis, fractured or not, requiring initiation of injectable bisphosphonate therapy as part of their care.
• Able to give informed consent to participate in the research.
• Affiliation to a Social Security system.

Exclusion Criteria

• Initial densitometry more than one year old.
• Patient receiving a treatment or food supplement containing magnesium (Mg).
• Contra-indication to the administration of Mg: hypersensitivity to magnesium carbonate or to one of the excipients.
• Patients with a magnesium level > 1.07 mmol/l.
• Patient with chronic renal failure, defined as creatinine clearance < 35 mL/min estimated by Cockcroft-Gault or glomerular filtration rate < 30 mL.min-1 estimated by CKD-EPI and taking into account which is more pejorative.
• Patient with a medical and/or surgical history deemed by the investigator or his 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 clermont-ferrand

Clermont-Ferrand, , France

Countries

France

Other Identifiers

2021-005401-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AOI 2021 ME_PICKERING

Identifier Type: -

Identifier Source: org_study_id