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

Early Phase 1

Completed

• Conditions: Osteoporosis, Age-Related
• Interventions: Drug: placebo; Drug: Atenolol; Drug: Nebivolol; Drug: Propranolol

• Registration Number: NCT02467400
• Lead Sponsor: Mayo Clinic

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.

Study Timeline

• Study First Submitted: 2015-06-04
• Study First Submitted QC: 2015-06-09
• Study First Posted: 2015-06-10
• Study Start: 2015-07-01
• Primary Completion: 2017-10-26
• Study Completion: 2018-04-01
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-04
• Last Update Posted: 2019-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 165

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	Sugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose
Atenolol	Atenolol	Atenolol 50 mg 1/day for 20 weeks
Nebivolol	Nebivolol	Nebivolol 5 mg/day for 20 weeks
Propranolol 40 mg	Propranolol	Propranolol 20 mg bid for 20 weeks
Propranolol 80 mg	Propranolol	Propranolol 40 mg bid for 20 weeks

Primary Outcome Measures

Name	Time	Method
Ratio of serum bone formation to bone resorption marker	20 weeks	Serum bone formation marker (PINP)/serum bone resorption marker (CTX)

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States