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Effects of Low-Dose Doxycycline on Oral Bone Loss

Primary Purpose

Periodontitis

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
20 mg doxycycline hyclate
Placebo
Sponsored by
University of Nebraska
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Periodontitis focused on measuring periodontitis, metabolic bone diseases, doxycycline

Eligibility Criteria

45 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Subjects will be female, postmenopausal and not receiving estrogen replacement therapy. Subjects will be 45-70 years old at the time of telephone screening. Subjects will have osteopenia (T-score of -1.0 to -2.5) of the lumbar spine or femoral neck as determined by dual-energy absorptiometry (DEXA) scans. Subjects will have a history of generalized moderate-advanced periodontitis and will be undergoing periodontal maintenance. Subjects will be in good general health and willing to sign the IRB-approved consent form. Exclusion Criteria: Subjects will not have an allergy or hypersensitivity to tetracyclines. Subjects will not have diseases or take medications that affect the inflammatory or immune responses (e.g., chronic use of non-steroidal anti-inflammatory drugs) or bone remodeling (e.g., drugs such as prescription estrogens, bisphosphonates, calcitonin or steroids). Subjects will not have any medical condition requiring antibiotic premedication (e.g., prosthetic heart valves, prosthetic joints, and mitral valve prolapse with regurgitation) for routine dental therapy. Subjects cannot have diabetes mellitus. Subjects cannot have had active periodontal therapy (quadrant scaling and root planing or periodontal surgery) within the past year. Subjects cannot have osteoporosis (T-score greater than -2.5) of the lumbar spine or femoral neck.

Sites / Locations

  • University of Nebraska Medical Center, College of Dentistry
  • Department of Oral Biology and Pathology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

low-dose doxycycline

Placebo

Arm Description

low-dose doxycycline (20 mg doxycycline hyclate)

Placebo

Outcomes

Primary Outcome Measures

Alveolar Bone Density
Alveolar bone density changes assessed by radiographic absorptiometry and computer-assisted densitometric image analysis.

Secondary Outcome Measures

Full Information

First Posted
August 1, 2003
Last Updated
September 1, 2023
Sponsor
University of Nebraska
Collaborators
National Institute of Dental and Craniofacial Research (NIDCR)
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1. Study Identification

Unique Protocol Identification Number
NCT00066027
Brief Title
Effects of Low-Dose Doxycycline on Oral Bone Loss
Official Title
Low-Dose Doxycycline Effects on Osteopenic Bone Loss
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
June 1, 2002 (Actual)
Primary Completion Date
October 1, 2005 (Actual)
Study Completion Date
October 1, 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nebraska
Collaborators
National Institute of Dental and Craniofacial Research (NIDCR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary purpose of this clinical trial is to determine whether low-dose doxycycline can reduce alveolar bone density loss in postmenopausal osteopenic women with periodontitis and not on hormone replacement therapy (i.e., estrogen deficient).
Detailed Description
The primary purpose of this clinical trial is to determine whether low-dose doxycycline (LDD) can reduce alveolar bone density loss in postmenopausal osteopenic women with periodontitis and not on hormone replacement therapy (i.e., estrogen deficient). The effects of LDD on alveolar bone height loss, progressive periodontal attachment loss, systemic bone mineral density, gingival crevicular fluid biochemical markers of collagen degradation and bone resorption and serum biomarkers of bone formation, bone resorption and inflammation also will be assessed. In addition, another objective is to determine if the microbial effects obtained with LDD over two years are equivalent to a placebo control. This clinical trial involves two clinical sites: the University of Nebraska Medical Center College of Dentistry and Stony Brook University School of Dental Medicine. A total of 128 postmenopausal osteopenic women with periodontitis between the ages of 45 and 70 at the time of telephone screening will be randomized to LDD or placebo groups and subjects will be followed for two years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontitis
Keywords
periodontitis, metabolic bone diseases, doxycycline

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
128 (Actual)

8. Arms, Groups, and Interventions

Arm Title
low-dose doxycycline
Arm Type
Experimental
Arm Description
low-dose doxycycline (20 mg doxycycline hyclate)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
20 mg doxycycline hyclate
Other Intervention Name(s)
antibiotic
Intervention Description
Subjects in the LDD group took 20 mg doxycycline hyclate tablets twice daily for two years
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
sugar pill
Intervention Description
Subjects in the placebo group took a placebo look-alike twice daily for two years.
Primary Outcome Measure Information:
Title
Alveolar Bone Density
Description
Alveolar bone density changes assessed by radiographic absorptiometry and computer-assisted densitometric image analysis.
Time Frame
Baseline, one-year and two-year visits

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects will be female, postmenopausal and not receiving estrogen replacement therapy. Subjects will be 45-70 years old at the time of telephone screening. Subjects will have osteopenia (T-score of -1.0 to -2.5) of the lumbar spine or femoral neck as determined by dual-energy absorptiometry (DEXA) scans. Subjects will have a history of generalized moderate-advanced periodontitis and will be undergoing periodontal maintenance. Subjects will be in good general health and willing to sign the IRB-approved consent form. Exclusion Criteria: Subjects will not have an allergy or hypersensitivity to tetracyclines. Subjects will not have diseases or take medications that affect the inflammatory or immune responses (e.g., chronic use of non-steroidal anti-inflammatory drugs) or bone remodeling (e.g., drugs such as prescription estrogens, bisphosphonates, calcitonin or steroids). Subjects will not have any medical condition requiring antibiotic premedication (e.g., prosthetic heart valves, prosthetic joints, and mitral valve prolapse with regurgitation) for routine dental therapy. Subjects cannot have diabetes mellitus. Subjects cannot have had active periodontal therapy (quadrant scaling and root planing or periodontal surgery) within the past year. Subjects cannot have osteoporosis (T-score greater than -2.5) of the lumbar spine or femoral neck.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey B Payne, DDS
Organizational Affiliation
UNMC College of Dentistry
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nebraska Medical Center, College of Dentistry
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68583-0740
Country
United States
Facility Name
Department of Oral Biology and Pathology
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794-8702
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18538066
Citation
Stoner JA, Payne JB. Interpretation of treatment effects in periodontal research: a note on the number needed to treat. J Can Dent Assoc. 2008 Jun;74(5):435-7. No abstract available.
Results Reference
background
PubMed Identifier
23649042
Citation
Salminen A, Pussinen PJ, Payne JB, Stoner JA, Jauhiainen M, Golub LM, Lee HM, Thompson DM, Sorsa T. Subantimicrobial-dose doxycycline treatment increases serum cholesterol efflux capacity from macrophages. Inflamm Res. 2013 Jul;62(7):711-20. doi: 10.1007/s00011-013-0626-z. Epub 2013 May 7.
Results Reference
result
PubMed Identifier
23205917
Citation
Payne JB, Nummikoski PV, Thompson DM, Golub LM, Stoner JA. The association between clinical and radiographic periodontitis measurements during periodontal maintenance. J Periodontol. 2013 Oct;84(10):1382-90. doi: 10.1902/jop.2012.120484. Epub 2012 Dec 3.
Results Reference
result
PubMed Identifier
23071896
Citation
Gu Y, Walker C, Ryan ME, Payne JB, Golub LM. Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine. J Oral Microbiol. 2012;4. doi: 10.3402/jom.v4i0.19227. Epub 2012 Oct 12.
Results Reference
result
PubMed Identifier
21357860
Citation
Payne JB, Golub LM, Stoner JA, Lee HM, Reinhardt RA, Sorsa T, Slepian MJ. The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. J Am Dent Assoc. 2011 Mar;142(3):262-73. doi: 10.14219/jada.archive.2011.0165.
Results Reference
result
PubMed Identifier
20937388
Citation
Payne JB, Golub LM. Using tetracyclines to treat osteoporotic/osteopenic bone loss: from the basic science laboratory to the clinic. Pharmacol Res. 2011 Feb;63(2):121-9. doi: 10.1016/j.phrs.2010.10.006. Epub 2010 Oct 16.
Results Reference
result
PubMed Identifier
20348487
Citation
Golub LM, Lee HM, Stoner JA, Reinhardt RA, Sorsa T, Goren AD, Payne JB. Doxycycline effects on serum bone biomarkers in post-menopausal women. J Dent Res. 2010 Jun;89(6):644-9. doi: 10.1177/0022034510363367. Epub 2010 Mar 26.
Results Reference
result
PubMed Identifier
20151804
Citation
Reinhardt RA, Stoner JA, Golub LM, Lee HM, Nummikoski PV, Sorsa T, Payne JB. Association of gingival crevicular fluid biomarkers during periodontal maintenance with subsequent progressive periodontitis. J Periodontol. 2010 Feb;81(2):251-9. doi: 10.1902/jop.2009.090374.
Results Reference
result
PubMed Identifier
18672990
Citation
Golub LM, Lee HM, Stoner JA, Sorsa T, Reinhardt RA, Wolff MS, Ryan ME, Nummikoski PV, Payne JB. Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women. J Periodontol. 2008 Aug;79(8):1409-18. doi: 10.1902/jop.2008.070623.
Results Reference
result
PubMed Identifier
17668979
Citation
Walker C, Puumala S, Golub LM, Stoner JA, Reinhardt RA, Lee HM, Payne JB. Subantimicrobial dose doxycycline effects on osteopenic bone loss: microbiologic results. J Periodontol. 2007 Aug;78(8):1590-601. doi: 10.1902/jop.2007.070015.
Results Reference
result
PubMed Identifier
21422479
Citation
Payne JB, Stoner JA, Lee HM, Nummikoski PV, Reinhardt RA, Golub LM. Serum bone biomarkers and oral/systemic bone loss in humans. J Dent Res. 2011 Jun;90(6):747-51. doi: 10.1177/0022034511402993. Epub 2011 Mar 21.
Results Reference
derived
PubMed Identifier
17716313
Citation
Payne JB, Stoner JA, Nummikoski PV, Reinhardt RA, Goren AD, Wolff MS, Lee HM, Lynch JC, Valente R, Golub LM. Subantimicrobial dose doxycycline effects on alveolar bone loss in post-menopausal women. J Clin Periodontol. 2007 Sep;34(9):776-87. doi: 10.1111/j.1600-051X.2007.01115.x.
Results Reference
derived
PubMed Identifier
17716312
Citation
Reinhardt RA, Stoner JA, Golub LM, Wolff MS, Lee HM, Meinberg TA, Lynch JC, Ryan ME, Sorsa T, Payne JB. Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: clinical outcomes. J Clin Periodontol. 2007 Sep;34(9):768-75. doi: 10.1111/j.1600-051X.2007.01114.x. Erratum In: J Clin Periodontol. 2007 Dec;34(12):1097. Lee, His-Ming [corrected to Lee, Hsi-Ming].
Results Reference
derived

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Effects of Low-Dose Doxycycline on Oral Bone Loss

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