Clinical trial NCT02355821: Comparative Effects of Moxonidine on Bone Metabolism, Vascular and Cellular Aging in Hypertensive Postmenopausal Women
Official title: Comparative Effects of Moxonidine and Bisoprolol on Bone Metabolism, Vascular and Cellular Markers of Aging, Blood Pressure in Hypertensive Postmenopausal Women (COMPASS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteopenia
Arterial Hypertension
Keywords: cellular aging
vascular aging
bone metabolism
collagen type 1 C-telopeptide
nuclear factor kappa-B ligand (RANKL)
pulse wave velocity
telomerase activity
Lead sponsor: National Medical Research Center for Therapy and Preventive Medicine
Sponsor class: OTHER_GOV
First posted: 2015-02-04
Enrollment: 114
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

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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

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Primary outcomes:
measure: Collagen Type 1 C-telopeptide
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
Secondary outcomes:
measure: Osteocalcin
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
measure: Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL).
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
measure: Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry
timeFrame: 12 months
measure: Telomerase Activity
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
measure: Pulse Wave Velocity (PWV)
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
measure: Intima-media Thickness (IMT)
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
measure: THe Number (Percentage) of the Treatment Responders
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
measure: Number of Participants With Adverse Events (AE)
timeFrame: baseline (Visit 1) and 12 months (Visit 4)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Research Center for Preventive Medicine
Study officials:
affiliation: tkacheva@rambler.ru
name: Olga N Tkacheva, Professor
role: PRINCIPAL_INVESTIGATOR
References: