Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03692026 |
| Other study ID # |
PERIO 1405 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 2018 |
| Est. completion date |
June 2020 |
Study information
| Verified date |
October 2018 |
| Source |
Cairo University |
| Contact |
Azza M Nasr, MSc |
| Phone |
+201003551727 |
| Email |
azzanasr81[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Placing implants immediately after tooth extraction offers several advantages such as
preventing bone resorption, maintaining alveolar crest width and height, reducing surgical
procedures and treatment time, in addition to good esthetic results. Immediate implant
placement after tooth extraction is often associated with a residual gap between the implant
surface and the residual bone walls. Osseointegration between the implant surface and the
surrounding osseous walls of the extraction socket should increase using materials that
promote new bone formation. Since both melatonin and hyaluronic acid are thought to have a
positive effect on increasing osseointegration and decreasing inflammation of the tissues;
the investigators want to test if adding a mix of hyaluronic acid and melatonin to
immediately implant, will give a better implant stability, decreased peri-implant bone loss
and decreased post-operative pain versus immediate implant placement without adding any
material.
Description:
Oral rehabilitation with dental implants has become an established therapy in the past
decades. Installation of implants in extraction sockets was advocated for to reduce the
number of surgical procedures, time between tooth removal and installation of implant
supported restoration, and to preserve the dimensions of alveolar ridge.
Scientific evidence exists demonstrating that early implantation may preserve the alveolar
anatomy and that the placement of a fixture in a fresh extraction socket may help to maintain
the bony crest structure. Fresh extraction sockets offer better opportunities for bone
regeneration because of their particularly elevated healing potential.
Implant stability is directly related to the percentage of the bone to implant contact area
(BIC). Studies had reported that osseointegration occurs following immediate implant
installation in extraction sockets despite presence of marginal gap between bone and implant
surface up to 4 mm. Different approaches have been introduced lately to positively enhance
the healing around dental implants. One approach to enhance osseointegration of dental
implants is the coating with organic components of the extracellular matrix. Recent studies
have shown promising results using different organic surface modifications on dental
implants, such as glycosaminoglycans, collagen and Hyaluronic acid.
Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycans which plays a
role in the inflammatory process and wound healing of mineralized and non-mineralized tissues
of the periodontium including granulation tissue formation and tissue remodeling. It also
supports the structural and homeostatic integrity of tissues regulating properties as osmotic
pressure and tissue lubrication.
It was found that coating the implants with low sulfated HA increased peri-implant bone
formation around dental implants in maxillary bone compared to uncoated implants in early
healing period. Another study proved that application of 1% HA associated with a collagen
scaffold can improve bone formation in critical-size defects.
Furthermore, Melatonin (N-acetyl-5-methoxy tryptamine) is a substance secreted by multiple
organs including the pineal gland, retina, bone marrow, the gastro-intestinal tract and the
immune system. It plays an anti-inflammatory, anti-oncotic, and immunomodulatory role by
scavenging free-radicals and by interacting with cell membrane and intracellular proteins. It
was found to have a positive effect on new bone formation around implants as it promotes
osteoblast differentiation and bone formation. Experimental evidence suggests that topical
application of melatonin may be useful in oral surgery and implant dentistry, increasing BIC
values and new bone formation, and so improving the success and long-term survival of the
implants.
Explanation for choice of comparators:
Since both melatonin and hyaluronic acid are thought to have a positive effect on increasing
osseointegration and decreasing inflammation of the tissues, the synergistic effect of both
materials on the following outcomes will be investigated; implant stability, decreasing the
horizontal dimensional bone loss around the implant and post-operative pain.
Aim of the study:
This study aims at assessing the effect of adding a mixture of hyaluronic acid and melatonin
to the implant surface in immediate implants; regarding implant stability, peri-implant
horizontal bone changes and post-operative pain, in comparison to immediate implant placement
without adding any materials.
The primary objective:
Measuring the implant stability in immediate implants with hyaluronic acid and melatonin
mixture, versus immediate implants placed without adding any materials.
The secondary objective:
Measuring the peri-implant horizontal bony changes and post-operative pain with topical
application of hyaluronic acid and melatonin mixture to immediately placed implants, versus
immediate implant placement without addition of any materials.
Trial design:
- A Randomized controlled trial.
- Unicenter study: A trial will be carried out in one hospital.
- Double blinded randomization: Neither the operator nor the patient will select the
method of treatment which will be chosen by the supervisor.
Methods:
A) Participants, interventions & outcomes
. Study settings: The study will be carried out on patients attending the outpatient clinics
in Oral Medicine, Diagnosis and Periodontology Department- Faculty of Oral and Dental
Medicine, Cairo University-Egypt.
. Eligibility criteria:
1. Inclusion criteria 1. Age: 18-60 years old. 2. Patients with single non-restorable teeth
in the inter-bicuspid area. 3. Patients with adequate bone volume for the dental implant
procedure. 4. Patients who are compliant to oral hygiene measures. 5. Patients accepting
to sign an informed consent to undergo the treatment.
2. Exclusion criteria:
1. Heavy smokers.
2. Systemic disease that contraindicates implant placement or surgical procedures.
3. No or poor patient's compliance.
4. Psychological problems.
5. Periapical pathosis at the site of intervention.
6. Pregnant females.
- Interventions General operative procedures Eligible patients will be divided
into two equal groups; study group (Immediate implant + hyaluronic acid and
melatonin mixture) and control group (immediate implant alone).
Preoperative measures (for both study and control groups): (T0)
- All subjects will pass through phase 0 therapy (T0) (Supragingival scaling,
subgingival debridement and oral hygiene instructions) before any surgical
procedure is performed.
- After 4 weeks, all subjects will be recalled for examination of their compliance to
the given oral hygiene instructions; tooth brushing twice daily and chlorhexidine
HCL 1.25% mouthwash (Hexitol mouthwash 100ml, ADCO, Alexandria, Egypt) twice daily.
- Eligible patients will be randomized before being enrolled in the study.
- The main investigator will take intraoral periapical radiographs at the time of the
initial examination to confirm the diagnosis of the non-restorable tooth site using
Kodak D speed films.
- CBCT scan using OnDemand 3D (Cybermed Inc., Technoville, Gasan-dong, Geumcheon-gu,
Seoul, South Korea) will be performed to record preoperative bone height and width
measurements used to determine implant diameter, length and position.
Surgical phase (T1):
1. The main investigator will perform all procedures under local anesthesia (4%
articaine with 1/200 000 adrenaline Solution) (Ubistesin forte 3M ESPE AG, ESPE
Platz, D-82229 Seefeld, Germany), using a local infiltration technique for
maxillary teeth or nerve block technique for mandibular teeth.
2. A loading dose of 2 capsules of Antibiotic 875 mg of Amoxicillin and 125 mg of
Clavulanic acid (2 X 1 gm Amoxicillin Clavulanate) will be given orally to the
patient 1 hour before the procedure.
3. Minimally invasive extraction of the intended tooth will be performed using
Periotome (Nordent,REPC N15, US) to preserve the alveolar bone integrity, followed
by irrigation of the socket with sterile saline solution and curettage to remove
any remnants of the periodontal ligaments or pocket tissue.
Intervention for study group (Group A):
4. Melatonin and hyaluronic acid mixture will be prepared (pure melatonin will be
purchased from pure bulk supplements and prepared as 5% oral gel at El-Ezaby
pharmacy. Hyaluronic acid will be used in the gel form Gingigel also from El Ezaby
pharmacy) The produced mixture will be added to the implant surface, into the
extraction socket and in the peri-implant area.
5. Implant will be inserted in site by flapless surgery.
6. Primary implant stability will be measured at the day of surgery and 6 months after
surgery using Ostell.
7. Simple interrupted suture with a 5-a silk suture to approximate the labial/buccal
and lingual/palatal tissues.
Intervention for control group (Group B):
4. Implant will be placed as in manufacturer instruction. 5. Primary implant stability
will be measured at the day of surgery and 6 months after surgery using Ostell.
6. Simple interrupted suture with a 5-a silk suture to approximate the labial/buccal and
lingual/palatal tissues.
Post-operative care: (T2) 1. Sutures will be removed after 10 days. 2. Patients in both
groups will receive restoration after implant being osseointegrated.
3. Post-operative pain will be assessed using Numerical scale for pain (NRS).
Follow-up (T0, T1, T2):
1. Patients will be recalled for follow up after 10 days, then every month to check on
the healing of the implantation site without complications (dehiscence, inflammation,
excessive pain), and to ensure that they are following proper oral hygiene measures.
2. At the same day of surgery, implant stability will be measured using Ostell (T1).
3. After 10 days, following suture removal, post-operative pain will be assessed using
the Numerical scale of pain (NRS).
4. After six months, implant stability will be measured again (T2) for all patients in
both groups. Also, all patients will do a CBCT to compare peri-implant horizontal bony
changes.
Prosthetic phase (T3):
1. After 6 months, implant exposure will be performed under local anaesthesia, and
healing collars will be placed for 1 week before being replaced by the permanent
abutment (T3).
2. Impressions (Express, 3M ESPE, 3 M Corporate Headquarters, Maplewood, Minnesota) will
be taken and fixed prosthesis will be fabricated accordingly.
Outcomes:
Primary outcome:
- Implant stability:
Implant stability quotient (ISQ) will be measured using Ostell, at the time of surgery
(T1) and after 6 months (T2).
Secondary outcomes:
- Peri-implant horizontal bone changes: Peri-implant horizontal bone measurements in mm
will be taken from pre-operative CBCT (T0) and post-osseointegration CBCT (T2) to assess
the change in the horizontal bone dimensions of the peri-implant area between the two
groups.
- Post-operative pain: Post-operative pain will be recorded for all patients using the
Numerical scale (NRS) of pain to compare between the values obtained for the study group
and those for the control group.
