Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT02467400

Collaborator

(none)

165

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to answer the question as to whether the sympathetic nervous system is an important determinant of bone metabolism in humans.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis, Age-Related	Drug: Atenolol Drug: Nebivolol Drug: Propranolol Drug: placebo	Early Phase 1

Detailed Description

In postmenopausal women, who have increased sympathetic outflow, to test the hypothesis that treatment with low doses of a non-selective β-blocker (propranolol) will increase serum markers of bone formation and reduce markers of bone resorption (Aim 1a); and using increasingly β1-AR (adrenergic receptor) selective blockers (atenolol and nebivolol), to better define the β-adrenergic receptor selectivity (β1 versus β2) in the regulation of bone turnover by sympathetic outflow in humans.

Study Design

Study Type:

Interventional

Actual Enrollment :

165 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism

Actual Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Oct 26, 2017

Actual Study Completion Date :

Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo Sugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose	Drug: placebo placebo
Active Comparator: Atenolol Atenolol 50 mg 1/day for 20 weeks	Drug: Atenolol beta blocker
Active Comparator: Nebivolol Nebivolol 5 mg/day for 20 weeks	Drug: Nebivolol beta blocker
Active Comparator: Propranolol 40 mg Propranolol 20 mg bid for 20 weeks	Drug: Propranolol beta blocker
Active Comparator: Propranolol 80 mg Propranolol 40 mg bid for 20 weeks	Drug: Propranolol beta blocker

Outcome Measures

Primary Outcome Measures

Ratio of serum bone formation to bone resorption marker [20 weeks]
Serum bone formation marker (PINP)/serum bone resorption marker (CTX)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:
at least 5 yrs since their last menses
Follicle Stimulating Hormone (FSH) > 20 IU/L
Exclusion Criteria:
Abnormality in any of the screening laboratory studies
Presence of significant liver or renal disease
Malignancy (including myeloma)
Malabsorption
Diabetes
Hypoparathyroidism
Hyperparathyroidism
Acromegaly
Cushing's syndrome
Hypopituitarism
Severe chronic obstructive pulmonary disease
Undergoing treatment with any medications that affect bone turnover, including the following:
adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)
anticonvulsant therapy (within the previous year)
pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)
calcium supplementation of > 1200 mg/d (within the preceding 3 months)
bisphosphonates (within the past 3 yrs)
denosumab
estrogen (E) therapy within the past year
treatment with a selective E receptor modulator within the past year
teriparatide within the past yr
anti-hypertensive therapy
Clinical history of osteoporotic fracture (vertebral, hip, or distal forearm
Recent (within the past 6 months) fracture
Serum 25-hydroxyvitamin D levels of < 20 ng/ml
Resting blood pressure >140/90 mm Hg or those with hypotension (systolic blood pressure <110 mm Hg), heart rate < 60 bpm
History of asthma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator: Sundeep Khosla, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sundeep Khosla, M.D., Professor of Medicine and Physiology, College of Medicine, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT02467400

Other Study ID Numbers:

14-004305

First Posted:

Jun 10, 2015

Last Update Posted:

Feb 6, 2019

Last Verified:

Feb 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by Sundeep Khosla, M.D., Professor of Medicine and Physiology, College of Medicine, Mayo Clinic

bone formation

Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 6, 2019