Bisphosphonate Therapy for Osteogenesis Imperfecta

• Sponsor: Indiana University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00159419
• Collaborator: (none)
• Enrollment: 18
• Arms: 2
• Duration (Months): 108

Study Details

Study Description

Brief Summary

The study is designed to evaluate the efficacy and safety of "Bisphosphonate Therapy for Osteogenesis Imperfecta (OI)." We, the researchers at Indiana University School of Medicine, are characterizing the changes effected by oral bisphosphonate therapy and comparing them to a regimen of intravenous bisphosphonate therapy in a group of children with OI and also in children with other disorders that result in low bone mass and fractures.

Condition or Disease	Intervention/Treatment	Phase
Osteogenesis Imperfecta; Osteoporosis; Paget Disease of Bone	Drug: Alendronate; Drug: Pamidronate	Phase 4

Detailed Description

The study is designed to evaluate the efficacy and safety of "Bisphosphonate Therapy for Osteogenesis Imperfecta (OI)." OI is an inherited disorder of collagen synthesis. Collagen is the major structural protein of the matrix of tendons, skin, and bones. Affected persons have low bone mineral density (and experience multiple fractures and progressive bony deformity). In its most severe form, the disorder is lethal in infancy. We plan to characterize the changes effected by oral bisphosphonate therapy and compare them to a regimen of intravenous bisphosphonate therapy in a group of children with OI.

Additionally, we have begun to treat patients with OI and other conditions of low bone mineralization for age who are not eligible for the standard protocol (too young, history of abdominal pain, etc.) with bisphosphonate. We also plan to screen the parents and siblings of our patients diagnosed with osteogenesis imperfecta, in order to determine if they also have osteoporosis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bisphosphonate Therapy for Osteogenesis Imperfecta
• Study Start Date: Aug 1, 1999
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alendronate 1 mg/kg po qd rounded to nearest 10 or 20 mg dose	Drug: Alendronate; Other Names: fosamax
Active Comparator: Pamidronate 3 mg/kg IV q4 months	Drug: Pamidronate

Outcome Measures

Primary Outcome Measures

1. Bone Mineral Density [2 years]

   By Dual-energy x-ray absorptiometry. Results were reported as z-scores as well as as absolute values. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate a better outcome", or similar, as accurate and appropriate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of OI, as defined by genetic analysis revealing a defect of type I collagen, OR by bone mineral density (BMD) <2.5 standard deviations (SD) for age plus two of the following:

• Family history of OI

• Frequent fractures

• Blue sclerae

• Multiple wormian bones on skull x-ray

• Hearing disturbance

• Dentinogenesis imperfecta

• Age between 3 and 21 years at the start of the study period.

• Children must be able to swallow whole tablets

• Parents of children must be able to understand protocol and give informed consent.

Exclusion Criteria:

• Therapy with bisphosphonates during the past 12 months.

• Other "non-traditional" therapy for OI in the last 6 months, such as growth hormone or anabolic steroids.

• Other chronic diseases besides OI that interfere with bone morphology or gastrointestinal absorption

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Indiana University School of Medicine

Investigators

• Principal Investigator: Linda A DiMeglio, MD, MPH, Indiana University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Linda DiMeglio, MD, MD, Indiana University
• ClinicalTrials.gov Identifier: NCT00159419
• Other Study ID Numbers: 9902-30
• First Posted: Sep 12, 2005
• Last Update Posted: Jun 14, 2017
• Last Verified: May 1, 2017

• Keywords provided by Linda DiMeglio, MD, MD, Indiana University: Osteogenesis Imperfecta; Fractures; Pediatric; Osteoporosis; Juvenile Pagets
• Additional relevant MeSH terms: Osteoporosis; Osteogenesis Imperfecta; Bone Diseases; Osteitis Deformans; Alendronate; Pamidronate

Study Results

Participant Flow

Recruitment Details	Recruited from clinics

Arm/Group Title	Pamidronate Treatment	Alendronate Treatment
Arm/Group Description
Period Title: Overall Study
STARTED	9	9
COMPLETED	9	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pamidronate Treatment	Alendronate Treatment	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	9	9	18
Age (Count of Participants)
<=18 years	9 100%	9 100%	18 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	8.4	9.0	8.7
Sex: Female, Male (Count of Participants)
Female	6 66.7%	5 55.6%	11 61.1%
Male	3 33.3%	4 44.4%	7 38.9%
Region of Enrollment (participants) [Number]
United States	9 100%	9 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Bone Mineral Density
Description	By Dual-energy x-ray absorptiometry. Results were reported as z-scores as well as as absolute values. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate a better outcome", or similar, as accurate and appropriate.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pamidronate Treatment	Alendronate
Arm/Group Description
Measure Participants	9	9
Mean (Standard Deviation) [z-score]	-1.3 (2.0)	-1.1 (1.2)

Adverse Events

Arm/Group Title	Pamidronate Treatment		Alendronate Treatment
Arm/Group Description	Acute phase reaction with infusion
All Cause Mortality
	Pamidronate Treatment		Alendronate Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pamidronate Treatment		Alendronate Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Pamidronate Treatment		Alendronate Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/9 (77.8%)		0/9 (0%)
General disorders
Acute Phase Reaction	7/9 (77.8%)	8	0/9 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.