Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal Women

Osteoporosis Clinical Trial

Official title:

Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00504166
• Other study ID #: M250
• Status: Completed
• Phase: Phase 4
• First received: July 17, 2007
• Last updated: July 31, 2013
• Start date: February 2006
• Est. completion date: April 2009

Study information

• Verified date: July 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the changes in bone structure as determined by magnetic resonance imaging measurements among early postmenopausal women after 24 months of treatment with alendronate, 70 mg once a week as compared to placebo

Description:

This is a randomized, double-blind, 24-month study. Fifty-five postmenopausal women, age range of 45-65 years, with low bone density will be recruited, with half of the subjects receiving alendronate + 2800 IU of vitamin D once weekly, the other half receiving placebo + 2800 IU of vitamin D once weekly. All study subjects will receive supplemental calcium 1000 mg/day + Vitamin D 400 IU/day. Measurements of microarchitecture will be made in the wrist, ankle, and hip, and the changes in trabecular bone will be assessed at 0, 12 and 24 months. Markers of bone turnover and bone mineral density (BMD) will be used to characterize the cohort and postmenopausal changes in bone turnover and density.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: April 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

Inclusion Criteria:

• early postmenopausal women

• 45-65 years old

• T-score range -1.1 to -2.5 either at the lumbar spine or any hip site exclusive of Ward's triangle

• at least 3 vertebrae rom L1-L4 must be evaluable

Exclusion Criteria:

• Those at high risk for osteoporotic fracture within the next 24 months, such that randomization to a placebo would be unacceptable (e.g., prior history of hip fracture, recent symptomatic clinical vertebral fracture, or very low BMD [i.e., BMD > 2.5 SD below young normal bone mass at any site exclusive of Ward's Triangle])

• Current excessive tobacco use

• Abnormality of the esophagus which delays esophageal emptying, such as stricture or achalasia

• Gastroesophageal reflux disease sufficient to require regular medication

• Inability to stand or sit upright for at least 30 minutes once a week

• Current use of any illicit drugs or has a history of drug or alcohol abuse within the past 5 years

• Current alcohol use > 3 drinks/day

• Any of the following: hypocalcemia; severe malabsorption syndrome; moderate or severe hypertension which is uncontrolled; new onset angina or myocardial infarction within six months of entry into the study; evidence for impaired renal function defined as creatinine clearance <35 ml/min or serum creatinine greater than 1.6 mg/dL; organ transplantation; or other significant end organ diseases (genitourinary, cardiovascular, endocrine, hepatic, psychiatric, renal, hematologic, or pulmonary) which, in the opinion of the investigator, may pose an added risk to the patient or impair the patient's ability to complete the trial

• History of or evidence for metabolic bone disease (other than postmenopausal bone loss) including but not limited to vitamin D deficiency (25-hydroxy-vitamin D level <10 ng/ml), hypoparathyroidism, recent hyperthyroidism (suppressed TSH within the six months prior to entry into the study), Paget's disease of bone, Cushing's disease, osteomalacia and renal osteodystrophy

• History of cancer. However, patients with the following cancers will be considered eligible for the study: 1) superficial basal or squamous cell carcinoma of the skin which has been completely resected; 2) other malignancies completely treated without recurrence or treatment in the last 5 years, with the following exceptions: patients with a history of breast cancer (including histologic diagnosis of lobular carcinoma in situ), endometrial carcinoma, or other known or suspected estrogen-sensitive neoplasia are excluded regardless of time since treatment or disease status

• Any treatment with a bisphosphonate or parathyroid hormone; within the last 6 months:

estrogen, estrogen analogues (e.g. raloxifene, tamoxifen) tibolone or anabolic steroids; Estrogen taken > 3 months ago for < 1 week is acceptable; Topical (vaginal) estrogen cream (< 2 g) used up to 2 times weekly is acceptable; Thyroid hormone, unless on a stable dose for at least six weeks before randomization with serum TSH within normal range; Fluoride treatment at a dose greater than 1 mg/day for more than 1 month at any time; given for a shorter time than one month it must have been greater than 1 year before randomization; Glucocorticoid treatment for more than one month with > 7.5 mg of oral prednisone (or the equivalent) per day within six months prior to randomization; patients who have received therapeutic glucocorticoids in the past must be considered highly unlikely to require retreatment with any dose of oral glucocorticoids for more than one month during the course of the study; Treatment with an immunosuppressant (e.g., cyclosporine, azathioprine) within the previous year.

• Current or expected treatment during the course of the study of any medication which might alter bone or calcium metabolism, including vitamin A in excess of 10,000 IU per day, or vitamin D in excess of 5,000IU per day, calcitonin, phenytoin, heparin, or lithium.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Osteopenia
• Osteoporosis

Intervention

Drug:
• alendronate sodium
alendronate sodium 70 mg tablet once week for 24 months

Other:
• placebo comparator
placebo to match alendronate sodium one tablet once a week for 24 months

Locations

Country	Name	City	State
United States	University of California Department of Radiology	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT	Trabecular number is a three-dimensional measure of the mean inter-trabecular distance; the primary micro-architectural feature measured by high-resolution CT imaging. The parameter was calculated from scans of the distal radius and distal tibia at baseline, 12, and 24 months. The percent change from baseline over these time periods was calculated as the primary outcome measure indicating the micro-architectural status of trabecular bone.	Baseline, 24 months	No