Biofunctionalization of a Volume-stable Collagen Matrix (VCMX) for the Treatment of Single Gingival Recession

• ClinicalTrials.gov Identifier: NCT05916742
• Recruitment Status: Recruiting
• First Posted: June 23, 2023
• Last Update Posted: June 23, 2023
• Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho
• Information provided by (Responsible Party): Mauro Pedrine Santamaria, Universidade Estadual Paulista Júlio de Mesquita Filho

Tracking Information

• First Submitted Date: June 14, 2023
• First Posted Date: June 23, 2023
• Last Update Posted Date: June 23, 2023
• Actual Study Start Date: April 15, 2022
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2023)

Gingival recession reduction (RecRed) [ Time Frame: 6 months ]

Final depth of gingival recession in millimeters minus gingival margin initial position in millimeters measured through a periodontal probe.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 14, 2023)

• Root coverage esthetic score [ Time Frame: 6 months ]
  The Root Coverage Esthetic Scale (RES; Cairo et al., 2009) will be performed by two blinded and independent examiners at the 6-month post-operative assessment. This score evaluates five variables: level of the gingival margin, marginal tissue contour, soft tissue texture, mucogingival junction alignment, and gingival color.
• Dentine hypersensitivity [ Time Frame: 6 months ]
  Evaluation of root sensitivity with the air blow test and measurement with a visual analog scale (VAS).
• Patient recovery [ Time Frame: 14 days ]
  Evaluation of postsurgery sequelae, pain, and discomfort, oral function and interference with daily activities through postoperative diary previously described (Tonetti et al. 2018).
• Patient-centred esthetic evaluation [ Time Frame: 6 months ]
  Esthetic evaluation performed by the patient through a visual analog scale (VAS).
• Immunological evaluation [ Time Frame: Baseline, 3, 7, 14, 30, and 60 days after surgery ]
  Gingival crevicular fluid will be collected in order to evaluate the levels of nine inflammatory markers: IL1β, IL4, IL5, IL6, IL9, IL10, IL17A, Interferon gamma-induced protein 10 kDa (IP10), macrophage inflammatory protein 1α (MIP1α), monocyte chemotactic protein 1α (MCP-1α), and tumor necrosis factor α (TNFα). The following growth factors will be evaluated: EGF, TGF, PDGF, FGF, and VEGF. In addition, MMP-1, MMP-2 from TIMP-1, and TIMP-2 will also be evaluated.
• Microbiological evaluation [ Time Frame: Baseline, 45 days, and 6 months after the procedure. ]
  The collection of the subgingival biofilm will be performed in order to quantificate microorganisms such as Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Fusobacterium nucleatum e Streptococcus sanguinis.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Biofunctionalization of a Volume-stable Collagen Matrix (VCMX) for the Treatment of Single Gingival Recession
• Official Title: Functionalization of a Volume-stable Collagen Matrix (VCMX) Using Injectable Platelet Rich Fibrin (i-PRF) for the Treatment of Single Gingival Recession
• Brief Summary: The treatment of single gingival recessions comprises different well-established techniques, and the association between coronally advanced flap (CAF) and the subepithelial connective tissue graft is considered the gold standard. However, despite the excellent clinical results obtained, the use of subepithelial connective tissue graft is related to an increased risk of trans and postoperative bleeding, a longer duration of the surgical procedure and greater postoperative pain and morbidity. To overcome these limitations and increase patient acceptance, new biomaterials have been developed as possible alternatives to the use of connective tissue graft. Recently, tissue engineering has been investigating collagen matrices as carriers of biologically active substances. In vitro and in vivo studies have shown that the biofunctionalization of these matrices using injectable platelet rich-fibrin (i-PRF) can optimize the healing process of soft tissues using own's patient regenerative components. However, although it has promising potential, clinical studies evaluating the performance of functionalized collagen matrices are still scarce in the literature. Thus, the present study aims to evaluate the clinical, esthetic, patient-centered, immuno and microbiological results of the use of the biofunctionalized volume stable collagen matrix (VCMX) for the treatment of single gingival recessions RT1. For such purpose, a randomized controlled clinical trial of superiority, parallel and blind will be carried out. Seventy-five patients with RT1 single gingival recession will be selected, who will be randomly allocated to one of the following groups: CAF+VCMX+i-PRF (n = 25), coronally advanced flap associated with VCMX functionalized with i-PRF; CAF+VCMX (n=25), coronally advanced flap associated with VCMX; and CAF group (n = 25), coronally advanced flap alone (CAF). The groups will be compared regarding clinical, esthetic and patient-centered outcomes at the baseline, three and six months after the surgical procedure. The microbiological evaluation will be performed at baseline, three and six months after surgery and the concentration of inflammatory markers and growth factors will be assessed before the procedure and 3, 7, 14, 30 and 60 days after treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Parallel assignment

Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Gingival Recession

Intervention

• Procedure: CAF
  Periodontal surgical technique to treat gingival recessions
  Other Name: Periodontal plastic surgery
• Procedure: i-PRF
  Blood-derived biomaterial. Two sterile plastic tubes (Process for PRF, Nice, France) with a volume of 10 ml will be used to generate fluid blood concentrate. After blood collection, the tubes will be centrifuged using a Duo centrifuge (Process for PRF, Nice, France) (fixed angle rotor with a radius of 110 mm) following the protocol proposed by Choukroun et al. (2018) (600 rpm; 8 min).
  Other Name: injectable platelet rich-fibrin
• Device: VCMX
  Porcine derived collagen matrix.
  Other Names:

  • Volume-stable collagen matrix
  • Geistlich Fibro-Gide
• Drug: Sodium dipyrone
  All participants will be instructed to take 500 mg sodium dipyrone just in case of pain.
  Other Name: Drug prescription
• Drug: Chlorhexidine rinse
  All participants will be instructed to perform 0.12% chlorhexidine rinse after the surgical procedures.
  Other Name: Drug prescription
• Drug: Amoxicillin 500mg
  Participants enrolled in the CAF+VCMX and CAF+VCMX will be instructed to take amoxicillin 500mg (8 hours/8 hours, during 7 days) after the surgical procedures.
  Other Name: Drug prescription

Study Arms

• Experimental: CAF+VCMX+i-PRF
  The surgical procedure for root coverage will be the trapezoidal-type of coronally advanced flap previously described (de Sanctis & Zucchelli 2007). Thus, it will start with two divergent releasing incisions lateral to the gingival recession defect. These releasing incisions will then be united by a sulcular incision, and the flap will be raised beyond the mucogingival junction. Subsequently, a VCMX functionalized with injectable platelet rich-fibrin (I-PRF) will be placed at the cemento-enamel junction (CEJ) level and stabilized in the adjacent interdental connective beds by interrupted sutures. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions.
  Interventions:

  • Procedure: CAF
  • Procedure: i-PRF
  • Device: VCMX
  • Drug: Sodium dipyrone
  • Drug: Chlorhexidine rinse
  • Drug: Amoxicillin 500mg
• Experimental: CAF+VCMX
  The surgical procedure for root coverage will be the trapezoidal-type of coronally advanced flap previously described (de Sanctis & Zucchelli 2007). Thus, it will start with two divergent releasing incisions lateral to the gingival recession defect. These releasing incisions will then be united by a sulcular incision, and the flap will be raised beyond the mucogingival junction. Subsequently, a VCMX will be placed at the cemento-enamel junction (CEJ) level and stabilized in the adjacent interdental connective beds by interrupted sutures. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions.
  Interventions:

  • Procedure: CAF
  • Device: VCMX
  • Drug: Sodium dipyrone
  • Drug: Chlorhexidine rinse
  • Drug: Amoxicillin 500mg
• Active Comparator: CAF
  The surgical procedure for root coverage will be the trapezoidal-type of coronally advanced flap previously described (de Sanctis & Zucchelli 2007). Thus, it will start with two divergent releasing incisions lateral to the gingival recession defect. These releasing incisions will then be united by a sulcular incision, and the flap will be raised beyond the mucogingival junction. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions.
  Interventions:

  • Procedure: CAF
  • Drug: Sodium dipyrone
  • Drug: Chlorhexidine rinse
  • Drug: Amoxicillin 500mg

Publications *

• Tonetti MS, Cortellini P, Pellegrini G, Nieri M, Bonaccini D, Allegri M, Bouchard P, Cairo F, Conforti G, Fourmousis I, Graziani F, Guerrero A, Halben J, Malet J, Rasperini G, Topoll H, Wachtel H, Wallkamm B, Zabalegui I, Zuhr O. Xenogenic collagen matrix or autologous connective tissue graft as adjunct to coronally advanced flaps for coverage of multiple adjacent gingival recession: Randomized trial assessing non-inferiority in root coverage and superiority in oral health-related quality of life. J Clin Periodontol. 2018 Jan;45(1):78-88. doi: 10.1111/jcpe.12834. Epub 2017 Nov 21.
• Cairo F, Rotundo R, Miller PD, Pini Prato GP. Root coverage esthetic score: a system to evaluate the esthetic outcome of the treatment of gingival recession through evaluation of clinical cases. J Periodontol. 2009 Apr;80(4):705-10. doi: 10.1902/jop.2009.080565.
• de Sanctis M, Zucchelli G. Coronally advanced flap: a modified surgical approach for isolated recession-type defects: three-year results. J Clin Periodontol. 2007 Mar;34(3):262-8. doi: 10.1111/j.1600-051X.2006.01039.x.
• Choukroun J, Ghanaati S. Reduction of relative centrifugation force within injectable platelet-rich-fibrin (PRF) concentrates advances patients' own inflammatory cells, platelets and growth factors: the first introduction to the low speed centrifugation concept. Eur J Trauma Emerg Surg. 2018 Feb;44(1):87-95. doi: 10.1007/s00068-017-0767-9. Epub 2017 Mar 10.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 14, 2023): 75
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 18, 2023
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Presence of RT1 (Cairo et al., 2011) buccal single gingival recession (GR) on vital upper or lower canines and premolars with intact root surface (visible CEJ).
• Presence of dentin hypersensitivity (HD) and/or esthetic concerns related to GR.
• Adults > 18 years old.
• Systemically health.
• No signs of active periodontal disease.
• Full-mouth plaque and bleeding score ≤ 20%.
• Written informed consent given.

Exclusion Criteria:

• Smoking.
• Contraindication for periodontal surgery.
• Pregnancy.
• Presence of orthodontic braces.
• Medications known to interfere with periodontal healing.
• Use of anticoagulants.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT05916742
• Other Study ID Numbers: VCMX+iPRF
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Mauro Pedrine Santamaria, Universidade Estadual Paulista Júlio de Mesquita Filho
• Original Responsible Party: Same as current
• Current Study Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Universidade Estadual Paulista Júlio de Mesquita Filho
• Verification Date: June 2023