Autologous Alveolar Bone Marrow Mesenchymal Stem Cells for the Reconstruction of Infrabony Periodontal Defects

NCT02449005 | Completed Phase 1

• 1 other identifier: ELKE-90467
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Systemically healthy periodontitis patients are recruited from new referrals to the Department of Periodontology and Biology of Implants, AUTh. After completion of non-surgical periodontal treatment those subjects who have at least one interdental osseous defect with probing pocket depth and clinical attachment level of ≥ 6mm and an intrabony component of ≥ 3mm with no endodontic or furcation involvement are randomly allocated into one of the three treatment groups. Group A receives regenerative treatment using autologous bone marrow mesenchymal stem cells free of animal derived reagents, produced in clean room facilities and seeded into collagen scaffolds enriched with fibrin glue; in Group B, a collagen fleece enriched with fibrin glue devoid of stem cells fills the osseous defect; Group C receives open flap debridement retaining the soft wall of the defect. Thereafter, subjects are followed for 12 months and are repeatedly assessed based on clinical, radiographic, immunological and microbiological parameters. In a series of cases, tissue engineering in a similar manner to Group A will be applied to treat isolated periodontal interdental defects, in combination with the novel "closed surgical technique".

Conditions

Chronic Periodontitis

Keywords

regeneration; stem cells; infrabony periodontal defect; fibrin glue; collagen fleece

Outcome Measures

Primary Outcomes (1)

• A reduction in the distance in mm from the bottom of the periodontal pocket to the cementoenamel junction using a manual probe (Hu-Friedy XP-23/QW, Hu-Friedy, Chicago, IL, USA) with 20-25g of pressure by a single calibrated examiner.

  Clinical data (gain in clinical attachment level (CAL))

  up to 12- months

Secondary Outcomes (1)

• A reduction in the distance in mm between the gingival margin and the bottom of the defect using a manual periodontal probe (Hu-Friedy XP-23/QW) by a single calibrated examiner.

  up to 12-months (baseline, 6-, 9-, 12- months)

Other Outcomes (4)

• A change in the distance in mm between the cementoenamel junction and the bottom of defect will be determined using a single evaluator.

  Baseline, 6-weeks & 3-, 6-, 9-, 12- months

• A change in the distance in mm between the bone crest to bottom of defect will be determined using a single evaluator.

  Baseline, 6-weeks & 3-, 6-, 9-, 12- months

• Composite measure of biomarkers will be examined to evidence the healing and immune response during the observation period

  Baseline, 6-weeks & 3-, 6-, 9-, 12- months

Study Arms (3)

Group A

EXPERIMENTAL

Group A (BM-MSCs/fibrin glue/collagen fleece) will receive regenerative treatment using autologous bone marrow mesenchymal stem cells free of animal derived reagents, produced in clean room facilities and seeded into collagen scaffolds enriched with autologous fibrin glue

Biological: BM-MSCs/fibrin glue/collagen fleece

Group B

EXPERIMENTAL

in Group B (Fibrin glue/collagen fleece), a collagen fleece enriched with autologous fibrin glue devoid of stem cells will fill the osseous defect

Other: Fibrin glue/collagen fleece

Group C

ACTIVE COMPARATOR

Group C will receive open flap debridement retaining the soft tissue wall of the pocket

Procedure: Open flap debridement

Interventions

BM-MSCs/fibrin glue/collagen fleece BIOLOGICAL

Xeno-free, clinical-grade, autologous alveolar bone marrow mesenchymal stem cells enriched with autologous fibrin glue and loaded into a commercially available collagen fleece.

Group A

Fibrin glue/collagen fleece OTHER

The biocomplex of autologous fibrin glue and collagen fleece devoid of stem cells will fill the osseous defect

Also known as: Procedure/Surgery/Growth factors

Group B

Open flap debridement PROCEDURE

Group C will receive minimally invasive surgery employing papilla preservation techniques in addition to retaining the soft tissue wall of the pocket. There will be no use of grafting materials

Group C

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Following non-surgical periodontal treatment, advanced chronic periodontitis patients, who are able to maintain plaque scores of less than 25% and have at least one deep infrabony defect with PPD and CAL of ≥ 6mm and an infrabony component of ≥ 3mm with no endodontic or furcation involvement as detected on the radiographs will be scheduled for surgery and will be followed for 12 months.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• University of Glasgow: collaborator

Study Sites (1)

Dental School, Aristotle University

Thessaloniki, 54124, Greece

Location

Related Publications (8)

• Bakopoulou A, Leyhausen G, Volk J, Koidis P, Geurtsen W. Comparative characterization of STRO-1(neg)/CD146(pos) and STRO-1(pos)/CD146(pos) apical papilla stem cells enriched with flow cytometry. Arch Oral Biol. 2013 Oct;58(10):1556-68. doi: 10.1016/j.archoralbio.2013.06.018. Epub 2013 Jul 18.

  PMID: 23871383 BACKGROUND

• Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res. 1999 Jun;8(2):135-60. doi: 10.1177/096228029900800204.

  PMID: 10501650 BACKGROUND

• Cortellini P, Tonetti MS. Minimally invasive surgical technique and enamel matrix derivative in intra-bony defects. I: Clinical outcomes and morbidity. J Clin Periodontol. 2007 Dec;34(12):1082-8. doi: 10.1111/j.1600-051X.2007.01144.x. Epub 2007 Oct 22.

  PMID: 17953696 BACKGROUND

• Cortellini P. Minimally invasive surgical techniques in periodontal regeneration. J Evid Based Dent Pract. 2012 Sep;12(3 Suppl):89-100. doi: 10.1016/S1532-3382(12)70021-0.

  PMID: 23040341 BACKGROUND

• Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7. doi: 10.1080/14653240600855905.

  PMID: 16923606 BACKGROUND

• Altman DG. Statistics in the medical literature: 3. Stat Med. 1999 Feb 28;18(4):487-90. doi: 10.1002/(sici)1097-0258(19990228)18:43.0.co;2-j. No abstract available.

  PMID: 10070688 BACKGROUND

• Apatzidou DA, Iliopoulos JM, Konstantinidis A, Verma M, Hardy P, Lappin DF, Nile CJ. Inflammatory and bone remodelling related biomarkers following periodontal transplantation of the tissue engineered biocomplex. Clin Oral Investig. 2024 Jun 7;28(7):361. doi: 10.1007/s00784-024-05754-8.

  PMID: 38847929 DERIVED

• Apatzidou DA, Bakopoulou AA, Kouzi-Koliakou K, Karagiannis V, Konstantinidis A. A tissue-engineered biocomplex for periodontal reconstruction. A proof-of-principle randomized clinical study. J Clin Periodontol. 2021 Aug;48(8):1111-1125. doi: 10.1111/jcpe.13474. Epub 2021 May 14.

  PMID: 33899259 DERIVED

MeSH Terms

Conditions

Chronic Periodontitis

Condition Hierarchy (Ancestors)

Periodontitis; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antonis Konstantinidis, Professor

  Dept. of Periodontology and Implant Biology, School of Dentistry, Aristotle University of Thessaloniki

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant, care provider, investigator/outcome assessor is not aware of the treatment modality
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 20, 2015
• Study Start: March 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 3, 2022

Record last verified: 2022-06

Locations

GR (1)