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

Primary Purpose

Osteoporosis, Age-Related

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atenolol
Nebivolol
Propranolol
placebo
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Osteoporosis, Age-Related focused on measuring bone formation

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

  • 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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

placebo

Atenolol

Nebivolol

Propranolol 40 mg

Propranolol 80 mg

Arm Description

Sugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose

Atenolol 50 mg 1/day for 20 weeks

Nebivolol 5 mg/day for 20 weeks

Propranolol 20 mg bid for 20 weeks

Propranolol 40 mg bid for 20 weeks

Outcomes

Primary Outcome Measures

Ratio of serum bone formation to bone resorption marker
Serum bone formation marker (PINP)/serum bone resorption marker (CTX)

Secondary Outcome Measures

Full Information

First Posted
June 4, 2015
Last Updated
February 4, 2019
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT02467400
Brief Title
Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism
Official Title
Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
July 1, 2015 (Actual)
Primary Completion Date
October 26, 2017 (Actual)
Study Completion Date
April 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Age-Related
Keywords
bone formation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
165 (Actual)

8. Arms, Groups, and Interventions

Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Sugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose
Arm Title
Atenolol
Arm Type
Active Comparator
Arm Description
Atenolol 50 mg 1/day for 20 weeks
Arm Title
Nebivolol
Arm Type
Active Comparator
Arm Description
Nebivolol 5 mg/day for 20 weeks
Arm Title
Propranolol 40 mg
Arm Type
Active Comparator
Arm Description
Propranolol 20 mg bid for 20 weeks
Arm Title
Propranolol 80 mg
Arm Type
Active Comparator
Arm Description
Propranolol 40 mg bid for 20 weeks
Intervention Type
Drug
Intervention Name(s)
Atenolol
Intervention Description
beta blocker
Intervention Type
Drug
Intervention Name(s)
Nebivolol
Intervention Description
beta blocker
Intervention Type
Drug
Intervention Name(s)
Propranolol
Intervention Description
beta blocker
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Ratio of serum bone formation to bone resorption marker
Description
Serum bone formation marker (PINP)/serum bone resorption marker (CTX)
Time Frame
20 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sundeep Khosla, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30153111
Citation
Khosla S, Drake MT, Volkman TL, Thicke BS, Achenbach SJ, Atkinson EJ, Joyner MJ, Rosen CJ, Monroe DG, Farr JN. Sympathetic beta1-adrenergic signaling contributes to regulation of human bone metabolism. J Clin Invest. 2018 Nov 1;128(11):4832-4842. doi: 10.1172/JCI122151. Epub 2018 Oct 2.
Results Reference
derived

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

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