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

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)”

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.

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.

Intervention(s) in this Clinical Trial

• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1 Alendronate, Calcium, Vitamin D
  • Crossover study. Year-1, 10 participants will take study medication, calcium and vitamin D supplements and other 10 participants will take placebo, calcium and vitamin D supplements. Year-2, they will crossover to the second arm of the study. Those who took study medication and supplements in year-1, will take placebo and supplements in the year-2, and those 10 participants who took placebo and supplements in the year-1, will take study medications and supplements in the year-2.
• Placebo Comparator: 2 Placebo, Calcium and Vitamin D
  • Year-1, 10 participants will take Alendronate (study medication)and calcium and vitamin D supplement). Another 10 participants will take placebo, calcium and vitamin D. In year-2 they will crossover. Those who took alendronate in the first year, will take Placebo, calcium and vitamin D for 12 months and those who took Placebo in the first year, will take Alendronate, calcium and vitamin D in the second year (12 months).

Primary Measures

• Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy
  • Time Frame: 12 months therapy
    Safety Issue?: No
• Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy
  • Time Frame: 24 months therapy
    Safety Issue?: No

Secondary Measures

• Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy
  • Time Frame: 12 months of therapy
    Safety Issue?: No
• Number of Participants With Improvement in BMD of Hip
  • Time Frame: 24 months of therapy
    Safety Issue?: No
• Participants With Atraumatic Fractures
  • Time Frame: 0 months
    Safety Issue?: No
• Participants With Atraumatic Fractures
  • Time Frame: 24 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 5 Years

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Medical University of South Carolina Other

Overall Clinical Trial Officials and Contacts

Deborah A Bowlby, M.D. Principal Investigator Medical University of South Carolina  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00259857

Study ID Number: 5 R01 FD001847-05

ClinicalTrials.gov Identifier: NCT00259857

Health Authority: United States: Food and Drug Administration