Atenolol for the Prevention of Osteoporosis (APO) (APO)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Atenolol 50 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tammie Volkman, RN; Phone Number: 507-538-6023; Email: volkman.tammie@mayo.edu
• Study Contact Backup: Name: Amanda Tweed; Phone Number: 507-255-6663; Email: tweed.amanda@mayo.edu

Study Locations

• United States
  • Maine
    • Scarborough, Maine, United States, 04074
      • MaineHealth
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atenolol; Study subjects will take Atenolol 50 mg daily over 2 years	Drug: Atenolol 50 MG; 50 mg Atenolol daily; Other Names: Atenolol
Placebo Comparator: Placebo; Study subjects will take a placebo daily over 2 years	Drug: Placebo; one placebo daily

What is the study measuring?

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
Additional secondary outcomes	Percent changes in radius and ultra-distal radius BMD using DXA, trabecular and cortical bone microarchitecture at the distal radius and tibia using HR-pQCT and in bone turnover markers (CTx, TRAP5b, PINP, osteocalcin).	Baseline, intermediate timepoints, 24 months

Collaborators and Investigators

• Sponsor: Sundeep Khosla, M.D.
• Collaborators: Columbia University; University of California, San Francisco; MaineHealth
• Investigators: Principal Investigator: Sundeep Khosla, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Atenolol
• Other Study ID Numbers: 18-005725

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No