Comparative Effects of Moxonidine on Bone Metabolism, Vascular and Cellular Aging in Hypertensive Postmenopausal Women

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparative Effects of Moxonidine and Bisoprolol on Bone Metabolism, Vascular and Cellular Markers of Aging, Blood Pressure in Hypertensive Postmenopausal Women (COMPASS)

Conditions
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Osteopenia, Arterial Hypertension

Intervention / Treatment
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* Drug: Moxonidine
* Drug: Bisoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female with age 45 years and older. Postmenopausal (absence of menstrual periods for a minimum of 12 months) at the moment of Informed Consent sign. Arterial hypertension grade I / II per ESH/ESC 2013 guidelines (diastolic pressure ≥ 90 and <110 mm Hg, systolic pressure ≥140 and <180 mm Hg). Not achieving BP targets <140/90 mmHg either during antihypertensive therapy or naive. Absence of moxonidine or bisoprolol treatment at least 6 months before the study 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. Signed Informed Consent for participation in the study - Exclusion Criteria: Hypersensitivity to moxonidine, bisoprolol or any other ingredient of the respective formulations Any Contraindications for moxonidine, bisoprolol Osteoporosis (Т-score below - 2.5 SD). Primary or secondary hyperparathyroidism. Paget's disease of bones. History of low traumatic bone fractures. Malabsorption syndrome. History of gastro-intestinal surgery. Severe disturbance of peripheral circulation. Raynaud's disease. Symptomatic (secondary) hypertension (caused by any primary internal diseases) Morbid obesity (BMI over 40 kg/m2). Symptoms of estrogen deficiency such as hot flushes, nights sweat, vaginal dryness Administration of any hormone-replacement therapy (HRT) or intake of isoflavones Secondary hypogonadism. Sistolic BP ≥180 mm Hg and/or Diastolic BP ≥110 mm Hg. Clinical presentations of cardiovascular disease: coronary heart disease (CHD), history of stroke, transient ischemic attack (TIA), Charcot's syndrome. Severe heart failure. Hemodynamically significant congenital heart disease. Heart rhythm disorders which require permanent use of any antiarrhythmic medications (including β-adrenoblockers and calcium antagonists). Diabetes mellitus of any genesis. Severe liver failure. Severe kidney failure including patients on dialysis Thyroid diseases accompanied by functional disorders (thyrotoxicosis or uncompensated hypothyroidism). Alcohol and drug abuse. Patients with oncological diseases diagnosed within 5 years before IC execution. Inability of the patient to comprehend the essence of the program and to provide his/her consent for participation in the program. Patients with any condition, which in the opinion of the Investigator makes the patient unsuitable for inclusion based on clinical judgment. Corticosteroid therapy 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 -
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moxonidine<br>0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID | Drug: Moxonidine<br>* 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<br>* Other names: Physiotens;|
| Active Comparator: Bisoprolol<br>5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID | Drug: Bisoprolol<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | baseline (Visit 1) and 12 months (Visit 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline (Visit 1) and 12 months (Visit 4) | 
| 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 | baseline (Visit 1) and 12 months (Visit 4) | 
| 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 | 12 months | 
| 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. | baseline (Visit 1) and 12 months (Visit 4) | 
| Pulse Wave Velocity (PWV) | Changes in mean pulse wave velocity (PWV) at final visit versus baseline level and in comparison between the groups | baseline (Visit 1) and 12 months (Visit 4) | 
| Intima-media Thickness (IMT) | Changes in mean intima-media thickness (IMT) at final visit in comparison between the groups. | baseline (Visit 1) and 12 months (Visit 4) | 
| 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. | baseline (Visit 1) and 12 months (Visit 4) | 
| Number of Participants With Adverse Events (AE) | Number of Participants with Adverse Events (AE) | baseline (Visit 1) and 12 months (Visit 4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cellular aging, vascular aging, bone metabolism, collagen type 1 C-telopeptide, nuclear factor kappa-B ligand (RANKL), pulse wave velocity, telomerase activity