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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Alendronate

Detailed Description

PROTOCOL OUTLINE:

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

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Alendronate for 12 months; Ten children will take alendronate 35mg or 70mg weekly depending upon the body weight for 12 months. Patients will also take calcium supplement daily.	Drug: Alendronate; Pill, 35mg or 70mg weekly, depending upon the body weight for 12 months.; Other Names: Fosamax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): October 1, 2003
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: February 1, 2001
• First Posted (Estimate): February 2, 2001

Study Record Updates

• Last Update Posted (Estimate): November 7, 2010
• Last Update Submitted That Met QC Criteria: October 21, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: rare disease; arthritis & connective tissue diseases; idiopathic juvenile osteoporosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Alendronate
• Other Study ID Numbers: 199/15705; FD-R-001847-01 (Other Grant/Funding Number: FDA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No