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Pentoxifylline and Tocopherol (PENTO) in the Treatment of Medication-related Osteonecrosis of the Jaw (MRONJ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03040778
Recruitment Status : Enrolling by invitation
First Posted : February 2, 2017
Last Update Posted : May 5, 2020
Sponsor:
Collaborators:
University of Alabama at Birmingham
New York Center for Orthognathic and Maxillofacial Surgery
Oregon Health and Science University
University of Michigan
Information provided by (Responsible Party):
Jasjit Dillon, University of Washington

Brief Summary:
The overall purpose of this project is to answer the following clinical question: Among Medication-Related Osteonecrosis of the Jaw (MRONJ) patients, do those who are treated with the Pentoxifylline and Tocopherol (PENTO) regimen and standard of care, when compared to those treated with standard of care alone, have decreased areas of exposed bone after one year of treatment?

Condition or disease Intervention/treatment Phase
Medication-related Osteonecrosis of the Jaw Bisphosphonate-related Osteonecrosis of the Jaw Avascular Necrosis Drug: Pentoxifylline Drug: Placebo Drug: Tocopherol Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pentoxifylline and Tocopherol (PENTO) in the Treatment of Medication-related Osteonecrosis of the Jaw (MRONJ): A Prospective, Randomized Controlled Trial to Evaluate a Novel Non-operative Treatment
Actual Study Start Date : April 1, 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: Standard of Care + PENTO
The current standard of care for MRONJ as outlined by the American Association of Oral and Maxillofacial Surgeons position paper based on stage of disease (Ruggiero 2014) AND PENTO regimen consisting of 400mg pentoxifylline (PTX) and 400IU tocopherol twice-daily PO for a total of 800mg/day PTX and 800 IU/day tocopherol
Drug: Pentoxifylline
Pentoxifylline is a commonly used medication for muscle pain associated with peripheral artery disease. It is a methylated xanthine derivative that improves peripheral blood flow, flexibility of red blood cell membranes, microcirculation, and tissue oxygenation and reduces viscosity of blood.
Other Names:
  • Pentoxifylline SR
  • Trental
  • Oxpentifylline

Drug: Tocopherol
Tocopherol (vitamin E) impairs tissue fibrosis and is a potent oxygen radical scavenger that may reduce damage caused by free radicals impacting necrosis.
Other Name: Vitamin E

Placebo Comparator: Standard of Care
The current standard of care for MRONJ as outlined by the American Association of Oral and Maxillofacial Surgeons position paper based on stage of disease (Ruggiero 2014). Placebo drugs to be taken in the control group 2 pills BID.
Drug: Placebo
Placebo tablets




Primary Outcome Measures :
  1. Change in Bone exposure area (mm^2) [ Time Frame: 0 months, 1 month, 3 months, 6 months, 9 months, 12 months ]

    The primary lesion's area of exposed bone will be estimated by measuring the greatest anterior-posterior and superior-inferior dimensions in millimeters (mm) of the site with the largest area of exposed bone present at the time of study enrollment.

    If there are multiple areas of exposed bone in a single patient, the site with the largest sum of linear anterior-posterior and superior-inferior dimensions will be included in the study.



Secondary Outcome Measures :
  1. Change in MRONJ Stage [ Time Frame: 0 months, 1 month, 3 months, 6 months, 9 months, 12 months ]
    MRONJ staging based on AAOMS Position paper staging criteria (Stage 0,1,2,3)

  2. Change in Pain [ Time Frame: 0 months, 1 month, 3 months, 6 months, 9 months, 12 months ]
    Visual analogue scale (VAS) measure of pain. A 100 mm scale will be used with 0 = no pain and 100 = worst pain ever. The patient will be asked to indicate their level of on the VAS.

  3. Change in osseous anterior-posterior linear dimension on orthopantomogram [ Time Frame: 0 months, 1 month, 3 months, 6 months, 9 months, 12 months ]
    Radiographic analysis. Greatest anterior-posterior linear dimension of osseous changes. A 5mm ball bearing will be used to standardize the measurement.

  4. Change in osseous superior-inferior linear dimension on orthopantomogram [ Time Frame: 0 months, 1 month, 3 months, 6 months, 9 months, 12 months ]
    Radiographic analysis. Dsi= Greatest superior-inferior linear dimension of osseous changes. A 5mm ball bearing will be used to standardize the measurement.

  5. Change in osseous area on orthopantomogram [ Time Frame: 0 months, 1 month, 3 months, 6 months, 9 months, 12 months ]
    Radiographic analysis. Change in area of osseous change. Will be according to the above formulae for shape; rectangle, circle, ellipse for the orthopantomogram imaging. A 5mm ball bearing will be used to standardize the measurement.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Stage 1, 2, or 3 MRONJ as defined by the AAOMS Position Paper on Medication-Related Osteonecrosis of the Jaw-2014 Update (Ruggiero 2014).
  2. History of exposure to antiresorptive medications such as bisphosphonates or RANK-L inhibitors
  3. Absence of tumor in the jaw at the time of recruitment
  4. Patients with the capacity to give informed consent

Exclusion Criteria:

  1. Patients with history of external radiation therapy to the jaws
  2. Patients who underwent any surgical intervention for MRONJ in the past 4 months
  3. Patients with past microvascular reconstruction of the head and neck
  4. Patients with an expected survival less than 1 year
  5. Patients with allergy or hypersensitivity to pentoxifylline, xanthines, or tocopherol
  6. Patients with planned invasive dental procedure in the next year
  7. Patients taking oral anticoagulants
  8. Patients with known hemorrhagic and coagulation disorder
  9. Patients with a vitamin K deficiency due to any cause
  10. Female patients who are pregnant or lactating
  11. Patients with history of serious bleeding or extensive retinal hemorrhage
  12. Patients with ischemic heart diseases, including, but not limiting, recent myocardial infarction
  13. Patients with serious cardiac arrhythmia
  14. Patient with history of prostate cancer
  15. Patients with severe liver disease
  16. Patients with severe renal failure (Creatinine clearance <30 mL/min)
  17. Patients with diagnosed hypotension
  18. Patients taking CYP1A2 inhibitors (e.g. ciprofloxacin, fluvoxamine)
  19. Diagnosis of MRONJ with no exposed bone
  20. Patient cannot tolerate impressions of exposed bone in a clinical setting, if needed.
  21. There is a change in the patient's clinical presentation (tooth extraction, sequestrectomy) from alginate impression, if impression is indicated.
  22. Any other situation or condition that, in the opinion of the INVESTIGATOR, may interfere with optimal PARTICIPATION in the study
  23. A patient who has taken both bisphosphonate and Denosumab

Information from the National Library of Medicine

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): NCT03040778


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35242
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-0018
United States, New York
New York Center for Orthognathic and Maxillofacial Surgery
Lake Success, New York, United States, 11042
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
University of Alabama at Birmingham
New York Center for Orthognathic and Maxillofacial Surgery
Oregon Health and Science University
University of Michigan
Investigators
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Principal Investigator: Jasjit Dillon, DDS, MBBS University of Washington
Publications:

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Responsible Party: Jasjit Dillon, Clinical Assistant Professor & Program Director, Oral & Maxillofacial Surgery, University of Washington
ClinicalTrials.gov Identifier: NCT03040778    
Other Study ID Numbers: STUDY00004779
First Posted: February 2, 2017    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Jasjit Dillon, University of Washington:
MRONJ
BRONJ
Additional relevant MeSH terms:
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Osteonecrosis
Bisphosphonate-Associated Osteonecrosis of the Jaw
Necrosis
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Jaw Diseases
Stomatognathic Diseases
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Pentoxifylline
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Radiation-Protective Agents
Vasodilator Agents
Free Radical Scavengers