Randomized Controlled Trial of Hyperbaric Oxygen in Patients Who Have Taken Bisphosphonates

Phase 1

Completed

• Conditions: Osteonecrosis
• Interventions: Device: hyperbaric oxygen; Device: non-treated control group

• Registration Number: NCT00462098
• Lead Sponsor: Duke University

Brief Summary

Osteonecrosis of the jaw (ONJ) has recently been recognized as associated with bisphosphonate therapy, however there is little information on the natural history, treatment or prevention strategies for this condition. The purpose of this study is to determine the effectiveness of hyperbaric oxygen as a treatment. We will randomize 35 out of 70 ONJ patients to receive HBO in addition to their routine oral surgery care and follow both groups over a 2-year period.

Detailed Description

Osteonecrosis of the jaw (ONJ) has recently been recognized as associated with bisphosphonate (BP) therapy, however there is little information on the natural history, treatment or prevention strategies for this condition1. Bisphosphonates, particularly compounds containing an aliphatic chain with an amino group in the R2 position, (pamidronate, alendronate and zoledronate) are extremely effective and widely used in the treatment of breast cancer, prostate cancer, multiple myeloma and non-malignant bone disease. Although ONJ appears to develop in less than one percent of patients taking these drugs, the seriousness of the disease plus the current lack of treatment options makes this a very difficult clinical problem This study will randomize 35 out of 70 patients to receive HBO in addition to their routine oral surgery therapy for ONJ and follow both groups over a 2-year period. The study design is an interventional, prospective, randomized trial with a 2-year follow up period. Seventy subjects meeting the inclusion criteria for ONJ will be recruited by participating physicians and randomized to receive 40 HBO treatments over a 4 week period or to continue their normal oral care. No subject, HBO treated or not, will be asked to change, initiate or discontinue any ongoing therapies they may be receiving from their primary care giver for ONJ or any other medical condition. The analysis will compare remission rates between the two groups while controlling for age, gender, race, previous local trauma or surgery, tumor type, diabetes, immunosuppression, bisphosphonate duration, indication (hypercalcemia), infection, corticosteroids, and thalidomide and dental hygiene. All subjects will be closely followed throughout the 24 month course of the study with weekly contacts by phone or email to log jaw pain level as well as to record any change in general medical condition. The 17 question Duke Health Profile will be used to measure quality of life indicators at 4 key points during the study.

Comparison(s): 1) clinical remission rate in patients receiving and not receiving HBO. 2) Bone turnover and molecular measures of osteoclast signaling in ONJ patients before and after HBO and relative to non-diseased controls (labs from non-diseased controls to be obtained from a companion study).

Study Timeline

• Study Start: 2006-08
• Study First Submitted: 2007-04-17
• Study First Submitted QC: 2007-04-17
• Study First Posted: 2007-04-18
• Primary Completion: 2010-12
• Study Completion: 2010-12
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-19
• Last Update Posted: 2013-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• Able to consent
• Meets definition of ONJ
• Has taken amino-bisphosphonates

Exclusion Criteria

• Unable to consent
• Ineligible for HBO
• Taking protease inhibitors for HIV
• Any past history of radiation to head or neck
• Life expectancy less than 12 months
• Tobacco use

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HBO	hyperbaric oxygen	Subject receives 40 HBO sessions at 2 atmospheres of pressure over 4 weeks
Control	non-treated control group	non-HBO comparison group

Primary Outcome Measures

Name	Time	Method
Clinical outcome assessments. Effect of HBO as an adjunct to the routine treatment of ONJ will be evaluated by physical exam and pain scores	Weekly for pain score. All others at: 3 months 6 months 12 months 18 months

Secondary Outcome Measures

Name	Time	Method
Quality of life measurements by the Duke Health Profile	3 months, 6 months, 12 months and 18 months
Laboratory measures of bone turnover	3 months, 6 months 12 months and 18 months
Molecular indicators of osteoclast activation (RANK, RANKL, OPG, pAKt)	3 months 6 months 12 months 18 months

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States