A Volumetric Analysis of Soft and Hard Tissue Healing for Ridge Preservation and Socket Seal After Tooth Extraction

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02844569
• Collaborator: Geistlich Pharma AG (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 19.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This study will be a randomized clinical trial involving a total of 24 subjects. The investigators propose to recruit subjects into 2 groups: 1) Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®), 2) Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). All subjects recruited will have already been approved and treatment planned for extraction + implant placement by non-study personnel to avoid any potential conflict of interest. All subjects will have radiographs that show the tooth planned for extraction. Each subject will be eligible for only 1 tooth extraction + dental implant rehabilitation. After tooth extraction, subjects will receive a standard site preservation therapy consisted with xenograft bone substitute + collagen dressing or the alternative site preservation therapy consisted with xenograft bone substitute + 3D-collagen matrix. After the conventional 6-month healing period, subjects will receive a dental implant in the previous extracted site. During the dental implant procedure, a 2x5mm bone core biopsy + a 2mm gingival biopsy will be obtained from the implant site. Biopsy samples will be stored for future histological and histochemical analysis. After dental implant placement, all subjects will receive a healing abutment for soft tissue healing prior to implant restoration.

During the 6-month healing time after tooth extraction and site preservation therapy, subjects will return at week-1, week-2, week-4, month-3, and month-6 for intra-oral scanning for soft tissue volumetric acquirement. Subjects will receive a Cone beam computed tomography (CBCT) prior to extraction for the baseline hard-tissue volume measurement and appropriate extraction planning and at 6-month post-extraction for volumetric measurement and appropriate implant treatment planning.

Hard tissue analysis will be performed to compare linear ridge remodeling (baseline vs. 6-month healing). CBCT images will be analyzed by non-contact reverse engineering system. Soft tissue volumetric analysis will be performed to compare the soft tissue healing between BioOss Collagen + Mucograft Seal and BioOss Collagen + Collagen Dressing. Images captured with an intra-oral scanner collected at baseline, week-1, -2, -4, month-3, and month-6.

Condition or Disease	Intervention/Treatment	Phase
Tooth Extraction	Device: Xenograft bone substitute; Device: Collagen dressing; Device: 3D-collagen matrix	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Volumetric Analysis of Soft and Hard Tissue Healing for Ridge Preservation and Socket Seal After Tooth Extraction
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Feb 28, 2018
• Actual Study Completion Date: Feb 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®).	Device: Xenograft bone substitute; Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site.; Other Names: BioOss Collagen® ; Device: 3D-collagen matrix; Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.; Other Names: Mucograft Seal®
Active Comparator: Control Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®).	Device: Xenograft bone substitute; Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site.; Other Names: BioOss Collagen® ; Device: Collagen dressing; Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.; Other Names: HeliPlug®

Outcome Measures

Primary Outcome Measures

1. Change in Buccal Plate Thickness From Baseline to Month 6 [6 months]

   The thickness difference between baseline and 6 months will be measured by the difference in mm using cone-beam computed tomography.

2. Change in Buccal Soft Tissue Volume Between Baseline and 6 Months [6 months]

   The soft tissue volume change between baseline and 6 months based on 3D images captured with intra-oral digital scanner.

3. Change in Buccal Bone Volume Between Baseline and 6 Months [6 months]

   The buccal bone volume change between baseline and 6 months will be calculated from cone-beam computed tomography data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects must be adult males or females age 18 to 80 years (inclusive).

• Subjects must be able and willing to follow study procedures and instructions in English.

• Subjects must have read, understood and signed an informed consent form in English.

• Subjects must have a maxillary premolar, canine, lateral incisor, or central incisor with a restorative or periodontal hopeless prognosis (Kwok and Caton 2007), in which an implant is indicated without any sinus lift required.

• Subjects undergoing implant placement should be in adequate periodontal health prior to implant placement. This includes having probing depth ≤ 4 mm for all remaining teeth at the same quadrant of the proposed implant placement. Patients with periodontal probing sites with probing depths of up to 5 mm may also be included if bleeding on probing in these sites is absent. Each subject should be considered to be periodontally stable prior to the implant surgery.

Exclusion Criteria:

• Individuals who have a chronic disease with oral manifestations.

• Individuals who exhibit gross oral pathology.

• The use of either antibiotics or chronic use (more than 7 days) of NSAIDs within 1 month prior to screening examination.

• Individuals that require antibiotic prophylaxis prior to dental treatment.

• Chronic treatment (i.e. two weeks or more) with any medication known to affect periodontal status (e.g. phenytoin, calcium antagonists, cyclosporine, Coumadin) within 1 month prior to screening examination.

• Uncontrolled diabetes mellitus (HbA1c >7) within 3 months prior to screening examination.

• Individual with uncontrolled parafunctional habits, such as clenching and bruxing on objects, that could adversely impact implant survival.

• Individuals with a history of intravenous bisphosphonates.

• Individuals with active infectious diseases such as hepatitis, HIV or tuberculosis.

• Current cigarette smokers.

• Individuals who are known to be pregnant, breastfeeding or planning to become pregnant within 6 months.

• Individuals with blood disorders (hemophilia) and /or currently taking anticoagulant medications, such as heparin, warfarin, or clopidogrel.

• Individuals receiving any therapy known to affect healing, such as high dose corticosteroids, radiation therapy or chemotherapy.

• Individuals allergic to topical or local anesthesia.

• Individuals who require maxillary sinus augmentation prior to dental implant therapy.

• Individuals with dehisced, fenestrated, or fractured labial/buccal alveolar bone plate determined after baseline CBCT or after tooth extraction where more than 50% of the buccal bone height is not present. In this case, if the surgeon determines that guided bone regeneration (bone graft and membrane) is needed to repair the defect, it will be done at no cost to the subject, but the subject will be excluded from the study protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	General & Oral Health Center	Chapel Hill	North Carolina	United States	27599-7450

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• Geistlich Pharma AG

Investigators

• Principal Investigator: Julie Marchesan, DDS, PhD, Assistant Professor Periodontology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 20, 2016

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02844569
• Other Study ID Numbers: 16-0832
• First Posted: Jul 26, 2016
• Last Update Posted: Feb 6, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by University of North Carolina, Chapel Hill: Dental Implants; Bone Grafting

Study Results

Participant Flow

Arm/Group Title	Test	Control
Arm/Group Description	Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. 3D-collagen matrix: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.	Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. Collagen dressing: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test	Control	Total
Arm/Group Description	Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. 3D-collagen matrix: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.	Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. Collagen dressing: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	45.2	56.4	50.8
Sex: Female, Male (Count of Participants)
Female	7 58.3%	7 58.3%	14 58.3%
Male	5 41.7%	5 41.7%	10 41.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 66.7%	9 75%	17 70.8%
Unknown or Not Reported	4 33.3%	3 25%	7 29.2%
Region of Enrollment (Count of Participants)
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Change in Buccal Plate Thickness From Baseline to Month 6
Description	The thickness difference between baseline and 6 months will be measured by the difference in mm using cone-beam computed tomography.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test	Control
Arm/Group Description	Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. 3D-collagen matrix: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.	Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. Collagen dressing: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.
Measure Participants	10	8
Mean (Standard Deviation) [mm]	1.85 (0.72)	1.25 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Change in Buccal Soft Tissue Volume Between Baseline and 6 Months
Description	The soft tissue volume change between baseline and 6 months based on 3D images captured with intra-oral digital scanner.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test	Control
Arm/Group Description	Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. 3D-collagen matrix: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.	Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. Collagen dressing: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.
Measure Participants	12	12
Mean (Standard Deviation) [mm^3]	68.6 (25.4)	87.6 (39.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Mixed Models Analysis
	Comments

3. Primary Outcome

Title	Change in Buccal Bone Volume Between Baseline and 6 Months
Description	The buccal bone volume change between baseline and 6 months will be calculated from cone-beam computed tomography data.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test	Control
Arm/Group Description	Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. 3D-collagen matrix: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.	Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. Collagen dressing: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.
Measure Participants	12	12
Mean (Standard Deviation) [mm^3]	72.6 (30.7)	60.9 (37.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	From time of extraction through 7 months after extraction
Arm/Group Title	Test		Control
Arm/Group Description	Extraction treated with xenograft bone substitute (BioOss Collagen®) + 3D-collagen matrix (Mucograft Seal®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. 3D-collagen matrix: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a 3D collagen matrix to cover the surgical site.		Extraction treated with xenograft bone substitute (BioOss Collagen®) + collagen dressing (HeliPlug®). Xenograft bone substitute: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket will be treated with xenograft bone substitute. At 6 months post-extraction a dental implant will be placed at the extraction site. Collagen dressing: Subjects requiring tooth extraction will have the hopeless tooth extracted. The extraction socket treated with xenograft bone substitute will receive a collagen dressing to cover the surgical site.
All Cause Mortality
	Test		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Test		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Test		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.