A Randomized Controlled Trial to Compare the Histomorphometric and Clinical Outcomes of Soft Tissue Augmentation at the Time of Lateral Ridge Augmentation Procedures
Phase: NA
Conditions: Bone Graft; Complications, Infection or Inflammation, Ridge Deficency, Dental Implant
Sponsor: University of Alabama at Birmingham

A randomized controlled Trial to Compare the 
Histomorphometric and Clinical Outcomes of Soft Tissue 
Augmentation at the Time of Lateral Ridge 
Augmentation Procedures. 
 
 
Study Protocol & Statistical Analysis Plan 
 
 
NCT03774888 
 
May 3, 2023 
 
 
 
Hussein Basma, DDS, MS, Principal Investigator 
 
University of Alabama at Birmingham 
Birmingham, Al 35294 
 
 

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A randomized controlled Trial to Compare the Histomorphometric and Clinical Outcomes of 
Soft Tissue Augmentation at the Time of Lateral Ridge Augmentation Procedures. 
 
Study Protocol  
1. Objectives/Specific Aims: 
The purpose of this investigator-initiated study is to evaluate the effect of soft tissue autogenous vs 
allogenic grafts on the soft tissue quantity and quality at the time of Guided Bone Regeneration (GBR) in 
preparation for endosseous implant placement.   
Autogenous Connective Tissue Grafting (CTG) and Acellular Dermal Matrix (ADM) soft tissue grafts are 
mainly used to alter the quality and quantity of soft tissue. 
a) Core objectives of this study are to: 
1) To evaluate the quality of soft tissue regenerated with the use of the two available soft tissue 
grafts      via histological analysis. 
2) To evaluate whether CTG or ADM influences the outcomes of Guided Bone Regeneration 
(GBR) procedures.  
3) To quantify the soft tissue augmentation achieved by the two available soft tissue grafts by 
direct clinical measurements after the healing  
b) Outcomes will be measured by an evaluation of the following: 
1) The quality of soft tissue regenerated with the use of the two available soft tissue graft via 
histological analysis (attachment to bone and keratinization) 
2) Keratinized tissue width (in mm) measured clinically with a periodontal probe from the implant 
collar to the mucogingival junction. 
3) Vertical thickness of soft tissue (in mm) measured clinically with periodontal probe around the 
implant collar from soft tissue surface to bone contact. 
4) Volumetric change of soft tissue dimensions around the implant collar evaluated by 
superimposition of pre- and post-grafting digital intra-oral scan. 
 
2. Background 
Dental rehabilitation of partially or totally edentulous patients with oral implants has become a routine 
treatment modality in the last decades, with reliable long-term results. Early loss of the teeth due to 
trauma or periodontitis often leads to deformities in these resulting edentulous ridges. Studies have 
demonstrated that bone resorption will occur secondary to tooth extraction. This tends to occur over a 
12-month period, most notably in the first 4 months following extraction.  
When a tooth or a group of teeth has been missing for a long time, the patient may present with a ridge 
that is deficient in thickness and/or height and inadequate for dental implant placement. In these cases, 
ridge augmentation using guided bone regeneration (GBR) is routinely used to regain the lost bone. 

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The concept of GBR is based upon the use of a barrier membrane to exclude rapidly growing soft tissue 
cells from a bony defect and, more importantly, to maintain a space for the slower process of bone 
formation. Bone grafts or bone substitutes are commonly used in GBR procedures to provide support for 
the barrier membrane, for additional space maintenance, and/or for their bone healing properties. 
 An important factor is flap closure during bone augmentation. The key to achieving wound closure is not 
only the clinician's ability to obtain tension-free release flap but also good soft tissue quality and 
quantity. In an attempt to achieve wound closure and hence graft stability, the buccal mucosa is often 
broadly released, and this often results in a severe apical translocation of the mucogingival line, loss of 
vestibule, and keratinized mucosa (KM). When the vestibule becomes shallow, it often leads to an 
esthetic challenge as well as a phonetics problem. Moreover, research has shown that areas with 
minimal KM often have a higher peri-implant plaque accumulation, inflammation, and attachment loss.  
Various surgical techniques have been used to obtain adequate amounts of keratinized tissue around 
dental implants, including the gingival autograft, apically positioned flap (APF), coronally positioned 
palatal sliding flap, and acellular dermal matrix graft (ADM). Performing a free gingival graft (FGG) prior 
to im- plant surgery has been suggested when there is minimal keratinized tissue over the edentulous 
ridge and APF and FGG can be combined in shallow vestibules with minimal keratinized tissue. A recent 
systematic review demonstrated that the combination of apically positioned flap and free gingival graft 
(FGG) is the most successful approach to increase the width of keratinized tissue and deepen the 
vestibule. However, when comparing the use of epithelialized gingival grafts with free connective tissue 
grafts, their ability to promote keratinized tissue is similar. 
These procedures are usually performed before implant placement or during the exposure of submerged 
implants, which can extend the healing period and result in patients suffering from pain and discomfort 
through several surgical stages. In addition, these can be time-consuming procedures in cases that 
already have good primary implant stability and do not need hard-tissue augmentation. 
To our knowledge, the influence of soft tissue augmentation at the time of ridge augmentation 
procedure has not been tested in socket grafting (ridge preservation) and ridge augmentation (deficient 
healed site) defects. This study aims at evaluating the effects of soft tissue augmentation using CTG or 
ADM on the clinical (amount) and histologic (% vital bone) outcomes at time of lateral ridge 
augmentation. 
 
3. Study Population, Protocol Procedure, and Method: 
 
Approximately 60 adults determined to need ridge augmentation graft of any ethnicity or gender with 
established UAB School of Dentistry Records may be enrolled in the study.   
Participants must be at least 18 years old with demonstrated ability to understand and consent to the 
proposed study procedure. Decisionally-impaired adults and/or minors who cannot consent for 
themselves will not be enrolled.  Women who report a current pregnancy or patients who are not 
systemically healthy enough to receive out-patient elective dental care at the time of enrollment will be 
excluded.  

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All attending faculty and residents in the UAB Department of Periodontology will be notified of this 
study.  Patients seeking dental implant therapy routinely present to the Periodontal clinic to have a 
consultation regarding ridge augmentation.  Upon completion of the exam by the periodontal resident 
faculty members will confirm the appropriate treatment plan (bone grafting).  If the patient is considered 
potentially eligible the PI will be asked to explain the study procedures and confirm eligibility based on 
the clinical and radiographic findings (inclusion criteria).  Candidates will be provided an unsigned copy 
of the consent form to take with them.  Participants will be given a minimum of 24 hours to decide upon 
participation.  Upon agreement for study entry patients will be scheduled by the research team for a 
screening visit, signing of the Informed Consent document and scheduling of the surgical procedure. 
Screening/baseline visit: Upon enrollment into the study the patient’s medical history and electronic 
records will be reviewed. Clinical examiners will conduct clinical and radiographic review/exams, the data 
will be used to determine eligibility according to the inclusion criteria. Study visits and objectives will be 
explained to all participants. IRB approved written informed consent will be obtained from all the 
participants.   
Surgical visit (Visit 1): Patients will be randomized like the flip of a coin to one of the three groups listed 
on the day of surgery. Randomly generated treatment groups will be printed on note cards and placed in 
sealed envelopes. Envelope will be opened during the visit. 
Group 1: Connective tissue graft (CTG) at time of lateral ridge augmentation, or  
Group 2: Acellular Dermal Matrix (ADM) at time of lateral ridge augmentation. 
Group 3: Control group (no soft tissue augmentation at time of lateral augmentation) 
 During bone augmentation procedure, just before suturing the flaps that were reflected, a CTG 
(Harvested from the patient’s palate) or ADM (donor tissue that is FDA approved) will be sutured to the 
membrane that covered the bone graft.  
Visit 2: The sutures will be removed after two weeks. Surgical sites (CTG, ADM or Control group) will be 
evaluated for healing status and postoperative instructions on resuming oral hygiene measures will be 
instructed to patients. Review medical history and assess for adverse events experience.  
Visit 3: Six months post-ridge augmentation, For the research purposes a soft tissue biopsy will be taken 
at the center of the augmented site after elevating the flap using a 2 mm tissue punch. It is noteworthy 
that this soft tissue specimen would have been typically drilled away (automatically discarded in the 
suction system) with the initial implant site preparation drill if a biopsy were not planned (regular clinical 
setting). Hence, the biopsy procedure will not affect in any negative way the likelihood of implant 
placement. One Soft tissue biopsy per every participant in each group will be harvested from the site 
that was augmented and each tissue sample will be labelled a unique set of numbers and/or letters. 
The soft tissue biopsy will be harvested and fixed in special solution overnight at 4°C. Fixed tissues will be 
dehydrated through an ethanol gradient, cleared in xylene, and embedded in paraffin. Embedded 
Tissues will be sagittal sectioned at 7mm thickness and mounted on Superfrost Plus slides (Fisher 
Scientific, Hampton, NH, USA). Serial sections of biopsy containing epithelia and connective tissue will 
then be cleared in xylene, rehydrated, and stained with hematoxylin and eosin (H&E) according to 

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standard protocol.  The samples will be store to the laboratory located in the Institute of Oral Health 
Research at UAB School of Dentistry for the analysis of the tissue samples. 
 
4. Inclusion/Exclusion Criteria: 
Inclusion Criteria 
Exclusion Criteria 
English speaking  
 
Non-English speaking 
At least 18 years old 
Less than 18 years old 
Must be a patient of the UAB Dental School  
Smokers/tobacco users (>10 cigarettes/day) 
Able to read and understand informed consent 
document. 
 
Patients 
with 
systemic 
pathologies 
or 
conditions 
contraindicating oral surgical procedures or adversely 
affecting wound healing. 
 
Need for implants to replace missing tooth or teeth 
in at least one quadrant of the mouth. 
Patients with significant medical conditions or habits expected 
to interfere with bony healing. 
 
Insufficient alveolar ridge width for endosseous 
implant placement defined as 5mm or less as 
determined by bone sounding and cone beam 
computed tomography (CBCT) scan.  
 
Patient is a poor compliance risk (i.e., poor oral hygiene, 
history of alcohol or drug abuse). 
Patient and/or guardian is willing and able to 
comply with the preoperative and postoperative 
diagnostic and clinical evaluations required. 
Bone dehiscence of >4mm following tooth extraction or 
Vertical loss of bone at edentulous ridge. 
Patient not pregnant or not breastfeeding. 
Patient pregnant or breastfeeding. 
 
 
 
5. Benefits 
 
Following a conventional lateral ridge augmentation, a displacement of the alveolar mucosa will take 
place because of the periosteal release that is part of the ridge augmentation procedure to achieve 
passive closure. Usually, this soft tissue defect that is created on the ridge where it will receive implants 
is corrected by a free gingival graft before, or at the time or after implant placement in order to create 
attached tissue adequate for future implant success. Benefits of this project is to monitor the expected 
benefits of using soft tissue grafting at the time of lateral ridge augmentation in creating a thicker tissue 
and possible attached soft tissue on the sites that will receive implants after the bone graft healing 
potentially leading to higher implant survival. This will decrease the number of surgeries and patient 
morbidity as the two procedures are going to be performed at the same visit. 
6. Risks 
Regarding procedural risks, due to each subject's physical and dental conditions being unique, the success 
of soft tissue grafting cannot be guaranteed. Some discomfort after treatment can be expected. 

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This may include pain, bleeding, inflammation, and soreness. These discomforts can be expected to 
go away within approximately 48 hours. The treatment site could become infected. If an infection occurs, 
the study dentist will treat the area. 
Risks in group 1, post-operative discomfort may be expected with harvesting of the CTG although there is 
a considerable variability in patient reported discomfort after having received the same treatment with 
either group. 
Risks associated with use acellular dermal matrix (group 2) include a low, theoretical possibility of viral or 
prion contamination of the materials. No such contamination has ever been reported and ADM has been 
used in many medical and dental applications. ADM is processed from cadaveric donor skin and all donors 
are tested for nondetectable levels of HIV and HepC. Furthermore, it is processed using proprietary methods 
to removal all cells and cellular components (and this is histologically verified for each processing batch) to 
allow the collagenous and extracellular framework to remain without the cells which may produce 
antigenicity. 
Regarding the randomization risk, patients will be assigned to a group by chance, which may prove to be 
less effective than the other. There is a chance that one procedure may have a risk of increased post-
operative discomfort, although there is considerable variability in patient reported discomfort after having 
received the same treatment with either group. 
There are no additional risks associated with the soft tissue biopsy in addition to those associated with the 
routine implant site preparation itself. The biopsy trephine will simply replace the initial implant drill, as it 
will have the same dimensions.  
Other risks associated with this protocol involve potential loss of confidentiality.  Precautions will be taken 
to ensure that patient confidentiality is maintained.  All records will be assigned identifying alphanumeric 
codes and the list linking identifying PHI to patient data will be kept on a password protected computer 
and destroyed immediately after statistical analysis is completed. All consent documents will be assigned 
non-identifying, alpha-numeric codes and the list linking personal information and patient data will be 
kept on a password protected computer and destroyed immediately after data analysis have been 
completed. 
There may be other risks that are unknown. 
 
7. Data Analysis/Outcome measures 
The null hypothesis is CTG and ADM materials will have the same soft tissue thickness and possible 
attached tissue (as demonstrated by histology) at time of implant placement. To reject the null 
hypothesis of equal means with a significance level (alpha) of 0.05 using a two-sided two-sample 
unequal-variance t-test, 22 patients in each group (total of 66) will reach 0.90 statistical power. 
Accounting for a 6-patient loss-to-follow up, 60 patients will be enrolled in the study. 
Outcomes will be measured by an evaluation of the following: 

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1) the quality of soft tissue regenerated with the use of the two available soft tissue grafts via 
histological analysis (attachment to bone and keratinization) 
2) Keratinized tissue width (in mm) measured clinically with a periodontal probe from the implant 
collar to the mucogingival junction. 
3) Vertical thickness of soft tissue (in mm) measured clinically with a periodontal probe around the 
implant collar from soft tissue surface to bone contact. 
4) Volumetric change of soft tissue dimensions around the implant collar evaluated by 
superimposition of pre- and post-grafting digital intra-oral scans  
 
8. Confidentiality 
Data will be stored in a password-protected study-specific computer database within the department of 
Periodontology.  The computer is backed-up by UAB IT. Knowledge of passwords and access to the 
database will be strictly limited to study personnel who are working with the collected data.   
 
9. Adverse Event Reporting 
 
Participants will be interviewed and instructed to call if they experience any adverse events after study 
procedures.  Such events will be recorded.  In the event of a serious adverse event, the IRB will be 
notified per posted requirements and in full compliance with federal guidelines for research in human 
subjects.