Atenolol for the Prevention of Osteoporosis (APO)

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

Official Title
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Beta1-Selective Blockade for Prevention of Postmenopausal Bone Loss: A Phase 2, Multi-Center, Double-Blinded, Randomized Placebo-Controlled Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: Atenolol 50 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Atenolol vs. Placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atenolol<br>Study subjects will take Atenolol 50 mg daily over 2 years | Drug: Atenolol 50 MG<br>* 50 mg Atenolol daily<br>* Other names: Atenolol;|
| Placebo Comparator: Placebo<br>Study subjects will take a placebo daily over 2 years | Drug: Placebo<br>* one placebo daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome: Percent change in femur neck bone mineral density (BMD) | Percent change in femur neck bone mineral density (BMD) by DXA | Baseline, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcomes: Percent changes in lumbar spine and total hip BMD | Percent changes in lumbar spine and total hip BMD | Baseline, 24 months |