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

Mayo Clinic

Status and phase: Completed; Early Phase 1

Conditions: Osteoporosis, Age-Related

Treatments: Drug: Atenolol; Drug: placebo; Drug: Propranolol; Drug: Nebivolol

Study type: Interventional

Funder types: Other

Identifiers

NCT02467400

14-004305

Details and patient eligibility

About

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

Full 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.

Enrollment: 165 patients

Sex: Female

Ages: 50 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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165 participants in 5 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo

Atenolol

Active Comparator group

Description:

Atenolol 50 mg 1/day for 20 weeks

Treatment:

Drug: Atenolol

Nebivolol

Active Comparator group

Description:

Nebivolol 5 mg/day for 20 weeks

Treatment:

Drug: Nebivolol

Propranolol 40 mg

Active Comparator group

Description:

Propranolol 20 mg bid for 20 weeks

Treatment:

Drug: Propranolol

Propranolol 80 mg

Active Comparator group

Description:

Propranolol 40 mg bid for 20 weeks

Treatment:

Drug: Propranolol