Clinical trial NCT00259857: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoporosis
Keywords: Fracture
Bone Mineral Density
DXA
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: FDA Office of Orphan Products Development
name: Merck Sharp & Dohme LLC
First posted: 2005-12-01
Enrollment: 22
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy
timeFrame: 12 months therapy
measure: Number of Participants With Improvement in Bone Mineral Density (BMD) of Spine After Therapy
timeFrame: 24 months therapy
Secondary outcomes:
measure: Number of Participants With Improvement in Bone Mineral Density (BMD) of Hip After Therapy
timeFrame: 12 months of therapy
measure: Number of Participants With Improvement in BMD of Hip
timeFrame: 24 months of therapy
measure: Participants With Atraumatic Fractures
timeFrame: 0 months
measure: Participants With Atraumatic Fractures
timeFrame: 24 months
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Deborah A Bowlby, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.