Phase II Study of Alendronate Sodium in Children With High-Turnover Idiopathic Juvenile Osteoporosis

Osteoporosis Clinical Trial

Official title:

A Non-Randomized, Open-Label, Prospective, Non-Controlled, 12-Month Clinical Trial to Determine the Effects of Alendronate 35 or 70 mg/Week Depending Upon Body Weight, in Children and Adolescent With IJO

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00010439
• Other study ID #: 199/15705
• Secondary ID: FD-R-001847-01
• Status: Completed
• Phase: Phase 2
• First received: February 2, 2001
• Last updated: October 21, 2010
• Start date: September 2000
• Est. completion date: November 2008

Study information

• Verified date: October 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

OBJECTIVES:

I. Determine the effects of alendronate sodium on skeletal remodeling and bone mineral density of the hip and spine in children with high-turnover idiopathic juvenile osteoporosis.

Description:

PROTOCOL OUTLINE:

Patients receive oral alendronate sodium weekly for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2008
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 14 Years

Eligibility

Eligibility Criteria:

• 5-14 years of age

• Weight 20 kg or greater

• History of one or more atraumatic fracture

• Sexual development no greater than Tanner II

• Osteoporosis by DXA (Diagnosis of high-turnover osteoporosis with no underlying cause (e.g., malignancy, hyperthyroidism, hyperparathyroidism, or vitamin D intoxication)

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%).

• Bone mineral density by DXA at 2 standard deviations (SD) below normal mean for age (Z-score at least 2 SD below normal mean at the lumbar spine or hip)

• 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 20kg and more

Exclusion Criteria:

• History of severe gastritis or reflux

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

• Abnormalities of the esophagus that delay emptying (e.g., strictures or achalasia)

• Hypersensitivity to bisphosphonates

• Uncorrected hypocalcemia

• History of gastric or duodenal ulcers

• Renal dysfunction as indicated by serum Creatinine greater than 1.5 mg/dL

• Liver dysfunction as indicated by serum SGPT greater than 2 times upper limit of normal for age or serum total bilirubin greater than 2.0 mg/dL

• Diagnosis of osteogenesis imperfecta (including family history) or blue sclerae or deafness

• Diagnosis of active rickets, osteomalacia, or bone alkaline phosphatase > 2 times normal for age

• Severe gastritis or reflux

• Pregnancy

• Anorexia Nervosa

• Prior/Concurrent Therapy—

• Prior course of prednisone allowed

• No concurrent prednisone except inhaled steroids

• No concurrent high-dose glucocorticoids

• No concurrent salmon calcitonin

• No other concurrent bisphosphonates

• No concurrent long-term anti-seizure medication

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Alendronate
Pill, 35mg or 70mg weekly, depending upon the body weight for 12 months.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, PMID: 12795371 2. P Madyastha, W Ries, B Hollis, F Reed, L Key. Alendronate improved bone mineral density in p

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Increased Bone Mineral Density	Number of participants with increase in bone mineral density at Lumbar Spine and/or Hip at 12 months as compared to the bone mineral density at Lumbar Spine and/or Hip obtained before therapy (baseline values)	at 12 months	No
Secondary	Participants (1) With Fractures Before and After Therapy,(2)Analysed for Average Changes From High to Near Normal Mineral Apposition Rate (MAR) After Therapy,(3)Analysed for Average Insignificant Changes in Biochemical Markers After Therapy.	Participants (pts) with fractures bef.and aft.therapy; pts analysed for average changes in mineral apposition rate (MAR) (high (1.9um/day) to near normal (1.2 um/day)as revealed in bone biopsies. MAR is the distance between the two tetracycline labels (um/day). The data represent the average of 10-17 measurements of the disltance obtained by reading 2-7 individual slides of bone biopsy and pts analysed for average insignificant biochemical markers (serum bone specific alkaline phosphatase for bone formation and urinary N-telopeptide for resorption)to determine the effect of therapy.	Before and 12 months after treatment with alendronate	Yes