Clinical trial NCT04905277: Atenolol for the Prevention of Osteoporosis (APO)
Official title: Beta1-Selective Blockade for Prevention of Postmenopausal Bone Loss: A Phase 2, Multi-Center, Double-Blinded, Randomized Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Healthy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Columbia University
name: MaineHealth
name: University of California, San Francisco
First posted: 2021-05-27
Enrollment: 420
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Atenolol vs. Placebo
Primary purpose: TREATMENT

Brief summary: Evaluate whether treatment with a widely used beta blocker, atenolol, will prevent bone loss at the lower back and hip in postmenopausal women.


Eligibility criteria: Inclusion Criteria:

* Able and willing to provide informed consent
* Postmenopausal women (FSH ≥ 16 IU/L) (no menses for at least one year)
* Aged 50-75 years

Exclusion Criteria:

* Clinical diagnosis of diabetes mellitus requiring insulin
* Clinically significant abnormality in any of the additional screening laboratory studies
* A1c- ≥8
* Calcium - \> upper limit lab value per site
* AST- 2x upper normal limit
* FSH- \< 16IU/L
* eGFR- \< 45 mL/min/1.73m2 based on creatinine
* CBC- Per PI interpretation of each patient
* Presence of (documented clinical diagnosis of any of the following):

  * Significant liver or renal disease
  * Malignancy (current diagnosis including myeloma or melanoma)
  * Radiation (the site PI will determine eligibility on a case-by-case basis)
  * Malabsorption (current clinical diagnosis or actively receiving treatment)
  * Hypoparathyroidism (current clinical diagnosis or actively receiving treatment)
  * Hyperparathyroidism (current clinical diagnosis or actively receiving treatment)
  * Acromegaly
  * Cushing syndrome
  * Hypopituitarism
  * Severe chronic obstructive pulmonary disease
  * Pheochromocytoma (current clinical diagnosis or actively receiving treatment)
  * History of cardiac failure
  * Ejection Fraction \<35% (based on most recent EF within the last 12 months, if available)
  * PR interval \> 200 msec on screening ECG or known heart block
  * History of bronchospastic disease with treatment (asthma, bronchitis)
  * Gastric Bypass
  * Parkinson's
  * Rheumatoid Arthritis
  * Psoriatic Arthritis
  * Connective Tissue disease
* Undergoing treatment with any medications that affect bone turnover, including the following:

  * adrenocorticosteroids (oral for \> 3 months within the past year or year-round use of inhaled corticosteroid use)
  * anticonvulsant therapy for seizures (carbamazepine, phenobarbital, or phenytoin within the previous year) pharmacological doses of: thyroid hormone (causing decline of thyroid stimulating hormone below normal, i.e. \< 0.3 miU/L) bisphosphonates (within the past 3 yrs; if taken orally \>1 month in past 3 years) denosumab, romosozumab, estrogen therapy (does not include creams or suppositories) or treatment with a selective estrogen receptor modulator, or teriparatide/abaloparatide (\> 1 month within the past year); aromatase inhibitors (\>1 month within the past year)
  * Current use of digitalis glycosides
  * Thiazides (\< 6 months of use prior to screening)
  * Current or within the past 3 months use of beta blockers
* Any recent fracture within the past 6 months prior to screening (other than fingers, toes and facial fractures, which are all acceptable)
* Bilateral hip replacements or metal in both hips
* Patients with serum 25-hydroxyvitamin D levels of \< 20 ng/ml, in order to ensure vitamin D sufficiency
* Resting systolic blood pressure \< 115 mm Hg, heart rate \< 55 bpm (average of 3 readings after a 5-minute rest and one minute between readings with an automatic cuff)

Primary outcomes:
measure: Primary Outcome: Percent change in femur neck bone mineral density (BMD)
timeFrame: Baseline, 24 months
Secondary outcomes:
measure: Secondary Outcomes: Percent changes in lumbar spine and total hip BMD
timeFrame: Baseline, 24 months
measure: Additional secondary outcomes
timeFrame: Baseline, intermediate timepoints, 24 months
Other outcomes:
Locations:
city: Scarborough
country: United States
facility: MaineHealth
state: Maine
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Mayo Clinic
name: Sundeep Khosla, MD
role: PRINCIPAL_INVESTIGATOR
References: