Biomarker Identification in Orthopaedic & Oral Maxillofacial Surgery Subjects to Identify Risks of Bisphosphonate Use
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|ClinicalTrials.gov Identifier: NCT01875458|
Recruitment Status : Recruiting
First Posted : June 11, 2013
Last Update Posted : May 30, 2019
Bisphosphonates are drugs that prevent bone loss by blocking the activity of cells that normally resorb bone. The most common examples of these drugs are Boniva and Fosamax. These drugs are available for oral or intravenous dosing and are prescribed at daily, weekly, biweekly, or monthly intervals. Among the many thousands of individuals who currently take these medications, certain individuals experience "atypical" femur fractures preceded by prodromal pain, changes in cortical thickening of bone, or bisphosphonate related osteonecrosis of the jaws (BRONJ). Osteonecrosis of the jaws is defined as exposed bone of the jaws for 8 weeks or more and requires surgical treatment.
This study will attempt to identify genomic and rna biomarkers that may play a role in differential metabolism of bisphosphonates or indicate tendency toward the severe adverse events associated with these drugs.
|Condition or disease|
|Osteoporosis, With or Without Treatment Bisphosphonate Treatment Atypical Femur Fracture Bisphosphonate Related Osteonecrosis of the Jaws (BRONJ) Healthy Volunteers|
|Study Type :||Observational|
|Estimated Enrollment :||500 participants|
|Observational Model:||Ecologic or Community|
|Official Title:||Biomarker Identification in Orthopaedic and Oral Maxillofacial Subjects|
|Study Start Date :||May 2013|
|Estimated Primary Completion Date :||April 2028|
|Estimated Study Completion Date :||April 2028|
Adults with current or past history of bisphosphonate treatment (exposed) with Bisphosphonate related Osteonecrosis of the Jaws (BRONJ), or, Adults with current or past history of bisphosphonate treatment (exposed) with atypical fracture
COUNTER MATCHED CONTROLS
Adults with current or past history of bisphosphonate treatment (exposed) without bisphosphonate related osteonecrosis of the jaws (BRONJ, or, Adults with current or past history of bisphosphonate treatment (exposed) with typical fracture or joint replacement or osteoporosis
Adults without current bisphosphonate treatment (unexposed) with Typical fracture (healthy fracture patients) Adults without current bisphosphonate treatment (unexposed) without BRONJ (healthy oral surgery subjects or adults with radionecrosis of the jaws)
Healthy Adult Volunteers
Healthy volunteers with or without current bisphosphonate treatment without jaw or extremity pathologies or injuries to contribute blood and saliva samples only.
- Absorption, Distribution, Metabolism, Excretion (ADME) Profiling of DNA from all sample types vs. normative data for the ADME panel and across study groups [ Time Frame: Baseline ]DNA analysis of saliva, blood, and tissues to detect differential response to drugs. DNA will be isolated from each sample and ADME profiling will be performed. Each participant subgroup will be compared to each other using ANOVA modeling. Each participant subgroup will be compared to normative data for the distribution of gene profiles in the general population for each probe on the ADME gene array.
- Differential expression of miRNA biomarkers across participant groups within the study [ Time Frame: Baseline ]The relative abundance of miRNA across each participant subgroup will be compared using ANOVA modeling. Each participant subgroup will be compared to normative data for the distribution of miRNA expression profiles in the general population for each probe when available.
- Microbiome (Bacterial and viral composition) of samples within and across participant groups will be assessed and compared to normative data. [ Time Frame: Baseline ]Using microbial genetic methods, we plan to determine the bacterial and viral diversity found in samples to evaluate the possible role of bacteria on the response to drugs. Microbiome metagenomics established within and across each participant subgroup will be correlated with ADME profiling results to assess the potential impact these two phenomena have on each other.
Biospecimen Retention: Samples With DNA
Saliva will be collected from online participants and DNA analysis will be performed.
Blood and tissue samples will be collected from in-person participants. DNA and RNA analysis will be performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01875458
|Contact: Brandon Eilberg, BSfirstname.lastname@example.org|
|Contact: Annamarie D Horan, MPA, PhDemail@example.com|
|United States, Pennsylvania|
|Online participation via https://www.surveymonkey.com/s/bisphos4ctg||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Patrick Hesketh 781-985-9556 Patrick.Hesketh@uphs.upenn.edu|
|University of Pennsylvania Health System||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Mary Dooley, PhD 215-294-9650 firstname.lastname@example.org|
|Contact: Annamarie D Horan, MPA, PhD 215-349-8856 email@example.com|
|Principal Investigator: Samir Mehta, MD|
|Principal Investigator: David C Stanton, MD, DMD|
|Principal Investigator:||Samir Mehta, MD||University of Pennsylvania, Department of Orthopaedic Surgery|
|Principal Investigator:||David C Stanton, MD, DMD||University of Pennsylvania, Department of Oral Surgery|
|Study Director:||Annamarie D Horan, PhD||University of Pennsylvania|