Gene Expression Variation and Implant Wound Healing Among Smokers and Diabetics

NCT01663298 | Completed

• 4 other identifiers: 10-11841R01DE021052-011UL1RR025747AWU
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Periodontal wound healing is a complex multifactorial process that involves interactions among various cells, growth factors, hormones and extracellular matrices. Although still poorly understood, these interactions trigger a series of events that lead to new tissue formation. One growth factor that plays an important role in wound healing is fibroblast growth factor 2 (FGF2). Many animal and human studies have shown this protein is effective in periodontal regeneration. Recently, epigenetic modifications, such as DNA methylation, have been associated with changes in patterns of gene expression. Preliminary data suggests that FGF2 gene may be differentially methylated in periodontal tissues. Aberrant gene promoter methylation in smokers and diabetics has also been reported in many studies. However, the role of DNA methylation in wound healing has not yet been investigated. The investigators hypothesize that the methylation status of FGF2 gene can affect the levels of FGF2 secreted during wound healing phase after dental implant surgery. The investigators also hypothesize there exists a difference in methylation levels of FGF2 gene in healthy, smoking and diabetic patients that can interfere with wound healing. The investigators seek to determine whether DNA methylation plays a role in wound healing and whether the methylation level of FGF2 gene varies among healthy, smoking and diabetic patients.

Conditions

Smoking; Diabetes

Keywords

DNA methylation; FGF2; Wound healing; Smoking; Diabetes; Implant

Outcome Measures

Primary Outcomes (1)

• FGF2 methylation level

  Genomic DNA is isolated from the collected gingival tissue samples. Methylation alterations in FGF2 are detected through differential methylation hybridization using the EpiTect® Methyl qPCR single assay.

  On the day of implant surgery

Secondary Outcomes (4)

• FGF2 mRNA expression level

  On the day of implant surgery (DAY 0)

• FGF2 protein level

  On the day of implant surgery (DAY 0) and 2, 4 and 6 weeks following implant surgery

• Implant stability quotient (ISQ)

  4 and 6 weeks following implant surgery

• Wound healing indices (WHI)

  2, 4 and 6 weeks following implant surgery

Study Arms (3)

Control group

Subjects must have never smoked and must be non-diabetic.

Procedure: Dental implant surgery

Smoking group

Subjects must have had at least 5 pack-years of self-reported smoking history, must be currently smoking and must be non-diabetic.

Procedure: Dental implant surgery

Diabetic group

Subjects must have type 2 diabetes. The condition must be diagnosed subjects must be treated by medications and/or insulin. A HbA1C test result either within past 3 months or performed in the first visit must be available. They must have never smoked.

Procedure: Dental implant surgery

Interventions

Dental implant surgery PROCEDURE

Surgery involving placement of one dental implant, of either Astra Tech or Straumann system, is performed in all subjects within 2 weeks of screening examination. Implant placement is 1-stage, but can be either on edentulous ridges or in extraction sockets.This is not a randomized treatment arm/group design. The study is observational with regards to the analysis of tissue samples that are collected prior to the routine placement of implants. The implant choice is based upon patient needs and is not related to any outcome.

Control group; Diabetic group; Smoking group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients in the graduate periodontal clinic in the school of dentistry at the University of North Carolina

You may qualify if:

• Adult males or females between the age of 18 and 70 years (inclusive)
• Able and willing to follow study procedures and instructions
• Have read, understood and signed an informed consent form
• In good general health
• Have one or more implant placements as their future treatment needs. The implant placement can be either as one-stage or two-stage, and can be either in an edentulous ridge or an extraction socket
• Qualify for enrollment into one of the three study groups
• Have probing depth ≤ 4 mm for all teeth at the same quadrant of implant placement. Sites with probing depth 5 mm will also be included if bleeding on probing in these sites are absent.

You may not qualify if:

• Have a chronic disease with oral manifestations
• Exhibit gross oral pathology
• Use of either antibiotics or NSAIDs within 1 month prior to screening examination
• Chronic treatment (i.e. two weeks or more) with any medication known to affect periodontal status (e.g. phenytoin, calcium, antagonists, cyclosporin, Coumadin) within 1 month prior to screening examination
• Systemic conditions, except smoking and diabetes, that are known to affect the periodontal status
• With active infectious diseases such as hepatitis, HIV or tuberculosis
• Known to be pregnant or breastfeeding

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Department of Periodontology, UNC School of Dentistry

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (13)

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  PMID: 16948560 BACKGROUND

• Murakami S, Takayama S, Ikezawa K, Shimabukuro Y, Kitamura M, Nozaki T, Terashima A, Asano T, Okada H. Regeneration of periodontal tissues by basic fibroblast growth factor. J Periodontal Res. 1999 Oct;34(7):425-30. doi: 10.1111/j.1600-0765.1999.tb02277.x.

  PMID: 10685372 BACKGROUND

• Murakami S, Takayama S, Kitamura M, Shimabukuro Y, Yanagi K, Ikezawa K, Saho T, Nozaki T, Okada H. Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs. J Periodontal Res. 2003 Feb;38(1):97-103. doi: 10.1034/j.1600-0765.2003.00640.x.

  PMID: 12558943 BACKGROUND

• Kitamura M, Nakashima K, Kowashi Y, Fujii T, Shimauchi H, Sasano T, Furuuchi T, Fukuda M, Noguchi T, Shibutani T, Iwayama Y, Takashiba S, Kurihara H, Ninomiya M, Kido J, Nagata T, Hamachi T, Maeda K, Hara Y, Izumi Y, Hirofuji T, Imai E, Omae M, Watanuki M, Murakami S. Periodontal tissue regeneration using fibroblast growth factor-2: randomized controlled phase II clinical trial. PLoS One. 2008 Jul 2;3(7):e2611. doi: 10.1371/journal.pone.0002611.

  PMID: 18596969 BACKGROUND

• Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009 May;88(5):400-8. doi: 10.1177/0022034509335868.

  PMID: 19493882 BACKGROUND

• Gomez RS, Dutra WO, Moreira PR. Epigenetics and periodontal disease: future perspectives. Inflamm Res. 2009 Oct;58(10):625-9. doi: 10.1007/s00011-009-0041-7. Epub 2009 May 8.

  PMID: 19440658 BACKGROUND

• Wilson AG. Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol. 2008 Aug;79(8 Suppl):1514-9. doi: 10.1902/jop.2008.080172.

  PMID: 18673005 BACKGROUND

• Ling C, Groop L. Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes. 2009 Dec;58(12):2718-25. doi: 10.2337/db09-1003. No abstract available.

  PMID: 19940235 BACKGROUND

• Krupanidhi S, Sedimbi SK, Vaishnav G, Madhukar SS, Sanjeevi CB. Diabetes--role of epigenetics, genetics, and physiological factors. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;34(9):837-45.

  PMID: 19779253 BACKGROUND

• Simmons RA. Developmental origins of diabetes: the role of epigenetic mechanisms. Curr Opin Endocrinol Diabetes Obes. 2007 Feb;14(1):13-6. doi: 10.1097/MED.0b013e328013da5b.

  PMID: 17940413 BACKGROUND

• Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, Mullen Y, Pfeifer GP, Ferreri K. Insulin gene expression is regulated by DNA methylation. PLoS One. 2009 Sep 9;4(9):e6953. doi: 10.1371/journal.pone.0006953.

  PMID: 19742322 BACKGROUND

• Han W, Wang T, Reilly AA, Keller SM, Spivack SD. Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients. Respir Res. 2009 Sep 25;10(1):86. doi: 10.1186/1465-9921-10-86.

  PMID: 19781081 BACKGROUND

• Belinsky SA, Palmisano WA, Gilliland FD, Crooks LA, Divine KK, Winters SA, Grimes MJ, Harms HJ, Tellez CS, Smith TM, Moots PP, Lechner JF, Stidley CA, Crowell RE. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res. 2002 Apr 15;62(8):2370-7.

  PMID: 11956099 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Gingival tissues, gingival crevicular fluid, saliva

MeSH Terms

Conditions

Smoking; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Behavior; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Silvana Barros, DDS, PhD, MS

  UNC Chapel Hill School of Dentistry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: August 13, 2012
• Study Start: August 1, 2010
• Primary Completion: January 12, 2016
• Study Completion: February 23, 2016
• Last Updated: February 12, 2020

Record last verified: 2019-02

Locations

US (1)