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

• Sponsor: National Research Center for Preventive Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02355821
• Collaborator: (none)
• Enrollment: 114
• Location: 1
• Arms: 2
• Duration (Months): 39.3
• Patients Per Site Per Month: 2.9

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Osteopenia; Arterial Hypertension	Drug: Moxonidine; Drug: Bisoprolol	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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 Start Date: Apr 1, 2015
• Actual Primary Completion Date: Jun 15, 2018
• Actual Study Completion Date: Jul 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Moxonidine 0.4 mg moxonidine QD titration up to 0.6 mg moxonidine BID	Drug: 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; Other Names: Physiotens
Active Comparator: Bisoprolol 5 mg Bisoprolol QD titration up to 7.5 mg Bisoprolol BID	Drug: 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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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

3. 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

4. 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.

5. 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

6. 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.

7. 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.

8. Number of Participants With Adverse Events (AE) [baseline (Visit 1) and 12 months (Visit 4)]

   Number of Participants with Adverse Events (AE)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Research Center for Preventive Medicine	Moscow		Russian Federation	101000

Sponsors and Collaborators

• National Research Center for Preventive Medicine

Investigators

• Principal Investigator: Olga N Tkacheva, Professor, [e-mail]

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Dec 12, 2014

More Information

Additional Information:

• 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
• 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

Publications

None provided.

• Responsible Party: National Research Center for Preventive Medicine
• ClinicalTrials.gov Identifier: NCT02355821
• Other Study ID Numbers: MOXOC001
• First Posted: Feb 4, 2015
• Last Update Posted: Sep 1, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by National Research Center for Preventive Medicine: cellular aging; vascular aging; bone metabolism; collagen type 1 C-telopeptide; nuclear factor kappa-B ligand (RANKL); pulse wave velocity; telomerase activity
• Additional relevant MeSH terms: Bone Diseases, Metabolic; Hypertension; Bisoprolol; Moxonidine

Study Results

Participant Flow

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	57	57
COMPLETED	57	57
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Moxonidine	Bisoprolol	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	57	57	114
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 56.1%	32 56.1%	64 56.1%
>=65 years	25 43.9%	25 43.9%	50 43.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.96 (9.1)	60.5 (9.1)	62 (9)
Sex: Female, Male (Count of Participants)
Female	57 100%	57 100%	114 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	57 100%	57 100%	114 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Russia	57 100%	57 100%	114 100%
Bone resorption marker (collagen type 1 C-telopeptide) (ng/ml) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ng/ml]	0.4	0.4	0.4

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	0.4	0.4
12 months	0.3	0.4

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	18.2	19.4
12 months	19.6	18.7

3. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	0.109	0.133
12 month	0.09	0.111

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Total hip BMD

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	-1.0	-0.55
12 months	-0.6	-1.2

5. Secondary Outcome

Title	Telomerase Activity
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	0.87	0.89
12 months	1.15	0.64

6. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	10.35 (2.56)	10.36 (2.47)
12 months	10.05 (2.29)	11.26 (2.6)

7. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Baseline	0.98 (0.17)	0.98 (0.15)
12 months	0.77 (0.14)	0.88 (0.16)

8. Secondary Outcome

Title	THe Number (Percentage) of the Treatment Responders
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Count of Participants [Participants]	55 96.5%	53 93%

9. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Moxonidine	Bisoprolol
Arm/Group Description	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	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
Measure Participants	57	57
Count of Participants [Participants]	3 5.3%	3 5.3%

Adverse Events

Time Frame	baseline (Visit 1) and 12 months (Visit 4)
Arm/Group Title	Moxonidine		Bisoprolol
Arm/Group Description	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		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
All Cause Mortality
	Moxonidine		Bisoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/57 (0%)
Serious Adverse Events
	Moxonidine		Bisoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Moxonidine		Bisoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/57 (5.3%)		3/57 (5.3%)
General disorders
headache	2/57 (3.5%)	2	1/57 (1.8%)	1
cough	0/57 (0%)	0	2/57 (3.5%)	2
Dry mouth	1/57 (1.8%)	1	0/57 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.