Clinical trial NCT02467400: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Osteoporosis, Age-Related
Keywords: bone formation
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2015-06-10
Enrollment: 165
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Ratio of serum bone formation to bone resorption marker
timeFrame: 20 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Sundeep Khosla, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.