Safety and Efficacy of Alendronate (Fosamax) in Children With Osteoporosis

Osteoporosis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Prospective, Cross-Over Phase II Clinical Trial to Determine the Safety and Efficacy of Alendronate (Fosamax) in Juvenile Osteoporosis (IND#60,017)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00259857
• Other study ID #: 5R01FD001847-05
• Secondary ID: FDR00184705-8304
• Status: Completed
• Phase: Phase 2
• First received: November 29, 2005
• Last updated: December 29, 2010
• Start date: October 2003
• Est. completion date: August 2009

Study information

• Verified date: December 2010
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

We have previously evaluated the safety and efficacy of Alendronate in 10 patients with juvenile osteoporosis during a 12-month clinical trial. We have documented that Alendronate improved BMD of the spine and hip without any major side effects. There were no additional fractures during therapy. The present study is designed to further evaluate the safety and efficacy of Alendronate in 20 children with juvenile osteoporosis using a double-blind, randomized, placebo-controlled, cross-over protocol.

Description:

Osteoporosis is an uncommon disease in children and early adolescents. Patients have a low bone mineral density, develop fractures with minimal or no trauma, and frequently have a negative family history. The disease results from either diminished bone formation or increased bone removal (resorption). No specific drug therapy has been recommended for juvenile osteoporosis. Alendronate (Fosamax) is effective in inhibiting bone resorption, increasing BMD and reducing fractures in adults with postmenopausal osteoporosis, but have not become established therapies in children. In the present study, we plan to evaluate the safety and efficacy of Alendronate in 20 patients with juvenile osteoporosis in a two-year period. This is a randomized, double-blind, placebo-controlled protocol. In the year-1, 10 patients will be assigned to receive Alendronate and 10 patients placebo. In the year-2, patients will be crossed over to the second arm of the study. Those who received Alendronate in the year-1, will receive placebo in the second year and vice verse. The patients will have 5 visits, the initial screening visit followed by 4 post therapy visits in a six-month interval. Measurements include DXA bone density scan of spine and hip, urinalysis and blood work.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: August 2009
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 15 Years

Eligibility

Eligibility Criteria:

• 5-15 yrs of age

• Weighing 20 kg and more

• History of multiple fractures

• Tanner stage II or less

• Osteoporosis by DXA.

Inclusion Criteria:

• Male and female children with a history of one or more atraumatic fractures, or evidence of one or more compression fractures on radiographs of the spine (reduction of >20 percent).

• Bone Mineral Density (BMD) determined by DXA sacn to confirm osteoporosis at a Z score greater than 2 SD (standard deviations) below the normal mean for age (Z score < -2 SD).

• Parental consent (and patient assent after age 12 years) to participate in the study.

• Sexual development at: Tanner stage II or less (Prepubertal stage).

• Weight = 20 kg and more.

Exclusion Criteria:

• History of severe gastritis or reflux.

• Abnormalities of the esophagus that delay emptying, such as strictures or achalasia

• Marked kyphoscoliosis or the inability to sit or stand for at least 30 minutes

• Hypersensitivity to bisphosphonates

• Uncorrected hypocalcemia

• History of gastric or duodenal ulcers

• Renal dysfunction as indicated by serum Cr >1.5 mg/dl.

• Liver dysfunction as indicated by serum SGPT > 2 times the upper limit for age or serum total bilirubin > 2.0 mg/dl.

• Diagnosis of osteogenesis imperfecta, a family history of osteogenesis imperfecta, blue sclerae or deafness.

• Diagnosis of active rickets or osteomalacia or serum bone alkaline phosphatase 2 times greater than normal for age.

• Pregnancy

• Anorexia Nervosa

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Alendronate
Group-1/Year-1:Alendronate, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight, for 12 months. Group-1/Year-2:Placebo, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight for 12 months. Group-2/Year-1:Placebo, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight for 12 months. Group-2/Year-2: Alendronate, pill, 35mg or 70mg, weekly; calcium, pill, 500mg or 1000mg daily; vitamin D, liquid, 800IU, daily, depending upon the body weight for 12 months.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of South Carolina	FDA Office of Orphan Products Development, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Key LL Jr, Ries W, Madyastha P, Reed F. Juvenile osteoporosis: recognizing the risk. J Pediatr Endocrinol Metab. 2003 May;16 Suppl 3:683-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy	Participants were screened for BMD of lumbar spine using DXA scan at visit 12 months after alendronate or placebo treatment.	12 months therapy	No
Primary	Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy	BMD of lumbar spine was measured using DXA scan at visit 24 months (Year-2)after alendronate or placebo treatment.	24 months therapy	No
Secondary	Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy		12 months of therapy	No
Secondary	Number of Participants With Improvement in BMD of Hip	Analysis was done per protocol and intention to treat.	24 months of therapy	No
Secondary	Participants With Atraumatic Fractures	Number of Participants with Atraumatic fractures before therapy.	0 months	No
Secondary	Participants With Atraumatic Fractures	Number of participants with fractures at the completion of therapy.	24 months	No