Back to results

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

Primary Purpose

Osteopenia, Arterial Hypertension

Status

Completed

Phase

Not Applicable

Locations

Russian Federation

Study Type

Interventional

Intervention

Moxonidine

Bisoprolol

About this trial

This is an interventional basic science trial for Osteopenia focused on measuring cellular aging, vascular aging, bone metabolism, collagen type 1 C-telopeptide, nuclear factor kappa-B ligand (RANKL), pulse wave velocity, telomerase activity

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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
-

Sites / Locations

National Research Center for Preventive Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Moxonidine

Bisoprolol

Arm Description

0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID

5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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

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

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.

Pulse Wave Velocity (PWV)

Changes in mean pulse wave velocity (PWV) at final visit versus baseline level and in comparison between the groups

Intima-media Thickness (IMT)

Changes in mean intima-media thickness (IMT) at final visit in comparison between the groups.

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.

Number of Participants With Adverse Events (AE)

Number of Participants with Adverse Events (AE)

Full Information

NCT ID

NCT02355821

First Posted

January 13, 2015

Last Updated

August 5, 2021

Sponsor

National Research Center for Preventive Medicine

1. Study Identification

Unique Protocol Identification Number

NCT02355821

Brief Title

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

Acronym

COMPASS

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

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

April 2015 (undefined)

Primary Completion Date

June 15, 2018 (Actual)

Study Completion Date

July 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Research Center for Preventive Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

114 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Moxonidine

Arm Type

Experimental

Arm Description

0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID

Arm Title

Bisoprolol

Arm Type

Active Comparator

Arm Description

5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID

Intervention Type

Drug

Intervention Name(s)

Moxonidine

Other Intervention Name(s)

Physiotens

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Bisoprolol

Intervention Description

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

Primary Outcome Measure Information:

Title

Collagen Type 1 C-telopeptide

Description

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)

Secondary Outcome Measure Information:

Title

Osteocalcin

Description

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)

Title

Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL).

Description

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)

Title

Bone Mineral Density (BMD) Using Control Dual-energy X-ray Absorptiometry

Description

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

Title

Telomerase Activity

Description

Time Frame

baseline (Visit 1) and 12 months (Visit 4)

Title

Pulse Wave Velocity (PWV)

Description

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)

Title

Intima-media Thickness (IMT)

Description

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)

Title

THe Number (Percentage) of the Treatment Responders

Description

Time Frame

baseline (Visit 1) and 12 months (Visit 4)

Title

Number of Participants With Adverse Events (AE)

Description

Number of Participants with Adverse Events (AE)

Time Frame

baseline (Visit 1) and 12 months (Visit 4)

10. Eligibility

Sex

Female

Accepts Healthy Volunteers

Eligibility Criteria

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 -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olga N Tkacheva, Professor

Organizational Affiliation

tkacheva@rambler.ru

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Research Center for Preventive Medicine

City

Moscow

ZIP/Postal Code

101000

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://elibrary.ru/item.asp?id=22652971

Description

The review of a new data is provided related to novel aspects of moxonidine use in the patients with arterial hypertension. The main attention is paid to the problem of vascular ageing, telomere biology and calcium-phosphorus homeostasis

URL

http://elibrary.ru/item.asp?id=21347559

Description

The aim was to assess the effects of moxonidine in terms of target blood pressure achievement; to identify potential additional benefits of moxonidine and its effects on bone metabolism and bone mineral density in postmenopausal women

Learn more about this trial

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

We'll reach out to this number within 24 hrs