Arterial Hypertension, Osteopenia
Conditions
Keywords
cellular aging, vascular aging, bone metabolism, collagen type 1 C-telopeptide, nuclear factor kappa-B ligand (RANKL), pulse wave velocity, telomerase activity
Brief summary
This study evaluates the effect of moxonidine versus bisoprolol on collagen type 1 C-telopeptide in postmenopausal female patients with arterial hypertension and osteopenia.
Detailed description
Several experimental studies have demonstrated that moxonidine may lower the activity of Na+- independent Cl-/bicarbonate exchanger (anion exchanger, AE) which plays an essential role in viability of osteoclasts that are crucial for bone resorption. The suppression of AE proteins activity has been proven to inhibit osteoclast activity and reduce bone resorption whereas the moxonidine molecule is known to reduce the AE protein activity. Therefore, the results of experimental studies have shown the ability of moxonidine to inhibit bone resorption through its effect on the osteoclast activity. Published data contain information on positive effects of beta-blockers on the bone tissue condition. There are data which clearly demonstrate a positive effect of beta-blockers on bone mass. The proposed trial is a comprehensive study of moxonidine effects on processes of cellular and vascular aging as well as bone metabolism.
Interventions
DRUGMoxonidine
0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID Other Names:perindopril 10 mg/day (optional); losartan 50 mg/day (optional); calcium carbonate; vitamin D
DRUGBisoprolol
5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID Other Names: perindopril 10 mg/day (optional); losartan 50 mg/day (optional); calcium carbonate; vitamin D
Sponsors
National Research Center for Preventive Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
1. Female with age 45 years and older. 2. Postmenopausal (absence of menstrual periods for a minimum of 12 months) at the moment of Informed Consent sign. 3. Arterial hypertension grade I / II per ESH/ESC 2013 guidelines (diastolic pressure ≥ 90 and \<110 mm Hg, systolic pressure ≥140 and \<180 mm Hg). 4. Not achieving BP targets \<140/90 mmHg either during antihypertensive therapy or naive. 5. Absence of moxonidine or bisoprolol treatment at least 6 months before the study 6. Osteopenia of lumbar spine and/or proximal part of the femur (osteoporosis T-score from -1 to -2.5 standard deviations \[SD\]) by X-Ray densitometry. 7. Signed Informed Consent for participation in the study \-
Exclusion criteria
1. Hypersensitivity to moxonidine, bisoprolol or any other ingredient of the respective formulations 2. Any Contraindications for moxonidine, bisoprolol 3. Osteoporosis (Т-score below - 2.5 SD). 4. Primary or secondary hyperparathyroidism. 5. Paget's disease of bones. 6. History of low traumatic bone fractures. 7. Malabsorption syndrome. 8. History of gastro-intestinal surgery. 9. Severe disturbance of peripheral circulation. 10. Raynaud's disease. 11. Symptomatic (secondary) hypertension (caused by any primary internal diseases) 12. Morbid obesity (BMI over 40 kg/m2). 13. Symptoms of estrogen deficiency such as hot flushes, nights sweat, vaginal dryness 14. Administration of any hormone-replacement therapy (HRT) or intake of isoflavones 15. Secondary hypogonadism. 16. Sistolic BP ≥180 mm Hg and/or Diastolic BP ≥110 mm Hg. 17. Clinical presentations of cardiovascular disease: coronary heart disease (CHD), history of stroke, transient ischemic attack (TIA), Charcot's syndrome. 18. Severe heart failure. 19. Hemodynamically significant congenital heart disease. 20. Heart rhythm disorders which require permanent use of any antiarrhythmic medications (including β-adrenoblockers and calcium antagonists). 21. Diabetes mellitus of any genesis. 22. Severe liver failure. 23. Severe kidney failure including patients on dialysis 24. Thyroid diseases accompanied by functional disorders (thyrotoxicosis or uncompensated hypothyroidism). 25. Alcohol and drug abuse. 26. Patients with oncological diseases diagnosed within 5 years before IC execution. 27. Inability of the patient to comprehend the essence of the program and to provide his/her consent for participation in the program. 28. Patients with any condition, which in the opinion of the Investigator makes the patient unsuitable for inclusion based on clinical judgment. 29. Corticosteroid therapy 30. Participation in any other clinical study during the whole course of this investigation including participation in a study within 30 days prior to providing the informed consent for this trial \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Collagen Type 1 C-telopeptide | baseline (Visit 1) and 12 months (Visit 4) | Changes in Median (Inter-Quartile Range) of the bone resorption marker (collagen type 1 C-telopeptide) at the end of the study from the baseline are evaluated in comparison between the groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL). | baseline (Visit 1) and 12 months (Visit 4) | Changes in Median (Inter-Quartile Range) values of the receptor activator of nuclear factor kappa-B ligand (RANKL) at final visit versus baseline level in comparison between the groups |
| Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry | 12 months | Changes in Median (Inter-Quartile Range) values of Bone mineral density (BMD) at final visit versus baseline level using control dual-energy X-ray absorptiometry and in comparison between the groups |
| Telomerase Activity | baseline (Visit 1) and 12 months (Visit 4) | Changes in Median (Inter-Quartile Range) telomerase activity at final visit versus baseline level in comparison between the groups Telomerase activity is measured in arbitrary units. Currently, there are no established reference values for telomerase activity in the world. Its activity is considered high or low in relation to the median. |
| Osteocalcin | baseline (Visit 1) and 12 months (Visit 4) | Changes in Median (Inter-Quartile Range) values of the bone synthesis marker (osteocalcin) at the end of the study (V4) from the baseline (V1) and to compare the values between the groups. |
| Intima-media Thickness (IMT) | baseline (Visit 1) and 12 months (Visit 4) | Changes in mean intima-media thickness (IMT) at final visit in comparison between the groups. |
| THe Number (Percentage) of the Treatment Responders | baseline (Visit 1) and 12 months (Visit 4) | Proportion of the treatment responders (defined as the proportion (%) of patients who achieved target blood pressure \<140/90 mmHg) after 8 and 48 weeks of the investigated treatment (V2, V3 and V4) and to compare the values between the groups. |
| Number of Participants With Adverse Events (AE) | baseline (Visit 1) and 12 months (Visit 4) | Number of Participants with Adverse Events (AE) |
| Pulse Wave Velocity (PWV) | baseline (Visit 1) and 12 months (Visit 4) | Changes in mean pulse wave velocity (PWV) at final visit versus baseline level and in comparison between the groups |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Moxonidine 0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID
Moxonidine: 0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID Other Names:perindopril 10 mg/day (optional); losartan 50 mg/day (optional); calcium carbonate; vitamin D | 57 |
| Bisoprolol 5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID
Bisoprolol: 5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID Other Names: perindopril 10 mg/day (optional); losartan 50 mg/day (optional); calcium carbonate; vitamin D | 57 |
| Total | 114 |
Baseline characteristics
| Characteristic | Moxonidine | Bisoprolol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 32 Participants | 64 Participants |
| Age, Continuous | 62.96 years STANDARD_DEVIATION 9.1 | 60.5 years STANDARD_DEVIATION 9.1 | 62 years STANDARD_DEVIATION 9 |
| Bone resorption marker (collagen type 1 C-telopeptide) | 0.4 ng/ml | 0.4 ng/ml | 0.4 ng/ml |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 57 Participants | 114 Participants |
| Region of Enrollment Russia | 57 participants | 57 participants | 114 participants |
| Sex: Female, Male Female | 57 Participants | 57 Participants | 114 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 3 / 57 | 3 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
Primary
Collagen Type 1 C-telopeptide
Changes in Median (Inter-Quartile Range) of the bone resorption marker (collagen type 1 C-telopeptide) at the end of the study from the baseline are evaluated in comparison between the groups
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moxonidine | Collagen Type 1 C-telopeptide | Baseline | 0.4 ng/ml |
| Moxonidine | Collagen Type 1 C-telopeptide | 12 months | 0.3 ng/ml |
| Bisoprolol | Collagen Type 1 C-telopeptide | Baseline | 0.4 ng/ml |
| Bisoprolol | Collagen Type 1 C-telopeptide | 12 months | 0.4 ng/ml |
Secondary
Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry
Changes in Median (Inter-Quartile Range) values of Bone mineral density (BMD) at final visit versus baseline level using control dual-energy X-ray absorptiometry and in comparison between the groups
Time frame: 12 months
Population: Total hip BMD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moxonidine | Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry | 12 months | -0.6 g/cm2 |
| Moxonidine | Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry | Baseline | -1.0 g/cm2 |
| Bisoprolol | Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry | Baseline | -0.55 g/cm2 |
| Bisoprolol | Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry | 12 months | -1.2 g/cm2 |
Secondary
Intima-media Thickness (IMT)
Changes in mean intima-media thickness (IMT) at final visit in comparison between the groups.
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moxonidine | Intima-media Thickness (IMT) | Baseline | 0.98 mm | Standard Deviation 0.17 |
| Moxonidine | Intima-media Thickness (IMT) | 12 months | 0.77 mm | Standard Deviation 0.14 |
| Bisoprolol | Intima-media Thickness (IMT) | Baseline | 0.98 mm | Standard Deviation 0.15 |
| Bisoprolol | Intima-media Thickness (IMT) | 12 months | 0.88 mm | Standard Deviation 0.16 |
Secondary
Number of Participants With Adverse Events (AE)
Number of Participants with Adverse Events (AE)
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moxonidine | Number of Participants With Adverse Events (AE) | 3 Participants |
| Bisoprolol | Number of Participants With Adverse Events (AE) | 3 Participants |
Secondary
Osteocalcin
Changes in Median (Inter-Quartile Range) values of the bone synthesis marker (osteocalcin) at the end of the study (V4) from the baseline (V1) and to compare the values between the groups.
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moxonidine | Osteocalcin | Baseline | 18.2 ng/ml |
| Moxonidine | Osteocalcin | 12 months | 19.6 ng/ml |
| Bisoprolol | Osteocalcin | Baseline | 19.4 ng/ml |
| Bisoprolol | Osteocalcin | 12 months | 18.7 ng/ml |
Secondary
Pulse Wave Velocity (PWV)
Changes in mean pulse wave velocity (PWV) at final visit versus baseline level and in comparison between the groups
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moxonidine | Pulse Wave Velocity (PWV) | Baseline | 10.35 m/s | Standard Deviation 2.56 |
| Moxonidine | Pulse Wave Velocity (PWV) | 12 months | 10.05 m/s | Standard Deviation 2.29 |
| Bisoprolol | Pulse Wave Velocity (PWV) | Baseline | 10.36 m/s | Standard Deviation 2.47 |
| Bisoprolol | Pulse Wave Velocity (PWV) | 12 months | 11.26 m/s | Standard Deviation 2.6 |
Secondary
Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL).
Changes in Median (Inter-Quartile Range) values of the receptor activator of nuclear factor kappa-B ligand (RANKL) at final visit versus baseline level in comparison between the groups
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moxonidine | Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL). | Baseline | 0.109 pmol/ml |
| Moxonidine | Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL). | 12 month | 0.09 pmol/ml |
| Bisoprolol | Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL). | Baseline | 0.133 pmol/ml |
| Bisoprolol | Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL). | 12 month | 0.111 pmol/ml |
Secondary
Telomerase Activity
Changes in Median (Inter-Quartile Range) telomerase activity at final visit versus baseline level in comparison between the groups Telomerase activity is measured in arbitrary units. Currently, there are no established reference values for telomerase activity in the world. Its activity is considered high or low in relation to the median.
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moxonidine | Telomerase Activity | Baseline | 0.87 arbitrary units |
| Moxonidine | Telomerase Activity | 12 months | 1.15 arbitrary units |
| Bisoprolol | Telomerase Activity | Baseline | 0.89 arbitrary units |
| Bisoprolol | Telomerase Activity | 12 months | 0.64 arbitrary units |
Secondary
THe Number (Percentage) of the Treatment Responders
Proportion of the treatment responders (defined as the proportion (%) of patients who achieved target blood pressure \<140/90 mmHg) after 8 and 48 weeks of the investigated treatment (V2, V3 and V4) and to compare the values between the groups.
Time frame: baseline (Visit 1) and 12 months (Visit 4)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moxonidine | THe Number (Percentage) of the Treatment Responders | 55 Participants |
| Bisoprolol | THe Number (Percentage) of the Treatment Responders | 53 Participants |