Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03029195 |
| Other study ID # |
AlexandriaU |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2016 |
| Est. completion date |
May 2022 |
Study information
| Verified date |
May 2022 |
| Source |
Alexandria University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The cleft lip and palate (CLP) is the commonest craniofacial anomaly worldwide. Nasoalveolar
molding (NAM) therapy has emerged in the management of CLP as an early presurgical
intervention to provide symmetry to severely deformed nasal cartilage, achieve projection to
the flattened nasal tip, provide nonsurgical elevation for the columella, improve alignment
of the alveolar ridge, reduce the cleft gap and it could significantly reduce the number of
secondary surgeries. Despite that NAM therapy is becoming the treatment option for early
cleft care, there is growing debate about its efficacy due to lack of quantitative assessment
of these findings. To provide the highest levels of clinical evidence on NAM therapy, there
has been international call for Randomized Controlled Clinical Trials.
Statement of the problem: lack of quantitative data about the efficacy of the NAM therapy for
unilateral CLP.
Aim of the study: is to develop a standardized non-invasive quantitative assessment for two
different techniques of the NAM therapy in Egyptian infants that involves 3D laser
scanning/CAD analysis for maxillary geometry, and nasal anthropometric analysis.
Methods Trial design: Prospective randomized controlled clinical trial (RCT). Settings: The
RCT will be performed through two phases; (Phase I: A controlled pre and post-RCT that will
be designed for the quantitative evaluation of the NAM therapy on the maxillary geometry),
and (Phase II: A post-test RCT will be designed for the quantitative evaluation of the NAM
therapy on the nasal anthropometry and comparing the outcome with the nasal anthropometry
that will be performed to age matched Egyptian norms).
Participants: 30 Egyptian infants with nonsyndromic UCLP will be randomly allocated to study
groups (Group I, n=15) that will undergo NAM therapy before the primary surgical repair, and
control group (n=15) that will undergo the primary surgical repair without NAM therapy. And
15 Egyptian infants will act as norm group.
Follow-up: (phase I- T0: before NAM, T1: after 1 month and T2: before surgery). (Phase II-
T"0: 10 days after surgery, and T"1: 6 months after surgery).
Description:
o Trial Design:
The present randomized controlled clinical trial (RCT) will be performed through two phases:
• RCT- (Phase I)
A controlled pre- and post-clinical trial will be designed for the quantitative evaluation of
the NAM therapy on the maxillary geometry.
• RCT- (Phase II)
A post-test controlled clinical trial will be designed for the quantitative evaluation of the
NAM therapy on the nasal anthropometry.
Infants with nonsyndromic complete unilateral cleft lip and palate UCLP will be selected from
those admitted to the Maxillofacial and Plastic surgery department- Faculty of Dentistry-
Alexandria University based on the inclusion and exclusion criteria.
- Sample size:
Using a power of 80% to detect clinically meaningful difference at the cleft gap distance
(D1-D2) before and after applying NAM therapy = 5.8, SD (standard deviation) =3.4, effect
size=1.2 and α=0.05. The minimal required sample size was calculated to be twelve per group
(increased to fifteen to avoid drop outs).
The sample size was calculated using G*Power software.
o Randomization:
The randomization for a total of 45 infants will be done as following:
Thirty infants with nonsyndromic UCLP will be randomly allocated by using closed envelop
allocation concealment method. However, the fifteen normal infants will be only randomly
selected.
RCT- (Phase I)
o Study group
(Group I): 15 infants In this group infants will undergo presurgical nasoalveolar molding
before the primary surgical correction
o Control group
(Group II): 15 infants This group, the infants will undergo primary surgical correction
without presurgical NAM procedures.
RCT- (Phase II)
- Norm group: (Group III): 15 infants Age matched noncleft infants. A group of normal age
matched noncleft infants will be randomly selected to act norms for the nasal
anthropometry for the Egyptian model, and will be compared with will be compared with
the study and the control groups.
• Procedures and Measurements:
1. Procedures
RCT- (Phase I)
1.1. Case history, examination, and diagnosis
1.2. Impressions and working cast:
Following evaluation and a thorough explanation of the treatment goals and the
procedure to the parents, an impression of an intraoral cleft defect will be made
using fast setting alginate impression material loaded on a custom made tray made
from wax.
With the infant fully awake and without any anesthesia in a clinical setting
prepared to handle an airway emergency with a surgeon present as a part of the
impression team.
During impression making, the infant will be held in an inverted position to keep
the tongue forward and to allow fluids to drain out of the oral cavity.
Once the impression material has been set, the tray will be removed, and the oral
cavity will be examined for the residual impression material in the cleft region.
Intraoral impressions will be carefully poured in regular dental stone, and the
casts will be recovered carefully.
1.3. Fabrication of the appliance:
The fabrication of the NAM appliance will be done following the technique described
by Grayson et al. It includes an intraoral molding acrylic palatal plate and a
nasal stent.
All casts will be marked and stored for measurements.
• The oral molding appliance:
The cleft region of the palate and alveolus will be filled in with wax to
approximate the contour and topography of an intact arch. The cast will be
duplicated to obtain a working cast on which two layers of wax will be adapted and
laboratory processed using clear heat-cure acrylic resin to fabricate the molding
prosthesis of 2 to 3 mm thickness to provide structural integrity and to permit
adjustments during the molding therapy.
The appliance will be finished and polished to ensure that all tissue borders are
smooth and that the oral portion of the appliance that would be in contact with the
dorsum of the tongue is given a high polish.
At the insertion appointment, the appliance will be carefully fitted in the
infant's oral cavity and observed for few minutes. The infant should able to suckle
without gagging or struggling.
- Extraoral retentive button:
An extraoral retentive button will be fabricated with self polymerizing clear
acrylic resin (*) and positioned facing downward on the labial flange, at an angle
40◦ relative to the plate, allowing clearance for upper and lower lips that will
facilitate the positive seating of the appliance to the palatal tissues.
The appliance will be then secured extraorally to the cheeks and bilaterally by
surgical tapes with orthodontic elastics at each end.
The use of skin barrier dressing tapes will be advocated to reduce cheek
irritation.
- Retentive taping with adhesive tapes and orthodontic elastics:
The skin barrier dressing tapes will be first applied to the infant's cheeks,
lateral and superior to the commissure.
These base tapes will also serve to anchor the thinner (0.25 × 4 inch) tapes of
suture strips used to hold the appliance against the palate.
Small orthodontic elastics (inner diameter 0.25 inch, wall thickness heavy) will be
incorporated into the loops of thinner tapes folded over them.
The elastic band will be placed over the retentive button, and the thinner tapes
will be pulled and secured to the base tapes on the infant's cheeks posteriorly and
superiorly.
An additional broader tape will be applied over the ends of the thinner tapes to
anchor suture strips and elastic bands to the base tapes.
The parents will be provided with detailed instructions on the proper method of lip
taping along with taping materials and adhesive. The patient will be recalled on a
weekly basis for follow-up.
Before any adjustments, the appliance will be cleaned with soap and water. Adhesive
tapes and elastics will be changed every week to maintain the proper activation
force to mold the alveolar segments. Instructions will be given to keep the
appliance in the oral cavity for 24 hours except during cleaning. The tissue
surface of the appliance will be modified to allow selective pressure on the
greater and lesser alveolar segments on either side of the cleft for correct
alignment.
- Nasal stent
Within the first month of treatment, the phase of active nasal cartilage molding
begins when the intraalveolar gap reduced to approximately 6 mm by incorporation of
the nasal stent component.
A nasal stent will be constructed from 0.019 inch round stainless steel wire. It
will be extended forward and then curved backward in the form of a "swan neck"
entering 3 to 4 mm past the nostril aperture.
Finally, the superior aspect of the nasal stent will be covered with a thin layer
of soft liner to ensure positive elastic pressure to the internal tissues of the
nasal dome.
The upper lobe will be inserted into the nose and gently lifted toward the dome
until a moderate amount of tissue blanching is evident. The lower lobe of the nasal
stent will lift the nostril apex and define the top of the columella. Periodic
examination of the tissues and adjustment of the appliance will be continued every
week to mold the nasoalveolar complex into the desired shape and position.
The endpoint for the treatment of patients with NAM will be when the inter-segment
distance will have been less than 3 mm and the nasal cartilages, columella, and
philtrum will have been properly repositioned, ensuring a clinically desirable
approximation of the alveolar segments.
The infant will scheduled for surgical repair with the plastic surgeon after
parents' consent.
1.4. Weekly adjustment visits
Weekly adjustments are required for maximum effectiveness of the presurgical
appliance. On each visit, a new impression will be taken and poured with dental
stone. This will be done to examine cleft closure and guide adjustment to the
appliance modifications. . Sporadic emergency appointments are also needed to
resolve any ulceration which may develop.
RCT- (Phase II)
1.5. Surgery
The primary surgical closure of the lip and nose will be performed at 3 months of
age.
The surgical technique will be performed according to Millard's
rotation/advancement technique. Because the alveolar segments will be in
approximation, a gingivoperiosteoplasty will be performed.
Digital photos with a submento-vertical view will be taken to the infants face
after the surgical closure. ( T"0 = 10 days post-surgery) and (T"1= 6 months
post-surgery).
2. Measurements:
2.1. Quantitative 3D maxillary geometric analysis.
2.2. Quantitative nasal anthropometric analysis on photographs. (Photogrammetry).
RCT- (Phase I)
2.1. Quantitative 3D maxillary geometric analysis:
The impressions for the maxillary casts that would have been taken at the initial
visit (T0; pre-NAM therapy), (T2 during NAM therapy) and (T3 before surgery) will
undergo 3D laser scanning and computer aided design (CAD) analysis.
The 3D models will be constructed using a laser scanning machine (3Shape) and 3D
software for CAD analysis.
Reference points and lines, which are based on the anatomic structures, will be
identified and digitized on the 3D model. The linear, angular, midline deviation,
distance, and curvature of the arch will be identified.
After laser scanning, the reference base plane will be set by. The plane containing
the points located at the incisal point (A) and the tuberosity points on the
noncleft and cleft sides (T1, T2) defined the XY-plane (horizontal reference
plane).
On the 3D image, the outline of the upper alveolar arch will be marked using six
points that contained the anatomical landmarks (D1, A, C1, M1, and T1 on the major
segment and D2, C2, M2, and T2 on the minor segment).
The curvature radius of the appropriate circle of the upper alveolar arch on each
major and minor segment (R and r, respectively) will be calculated using the
software.
The symmetry of the upper alveolar arch will be analyzed by calculating the ratio
of the curvatures of the upper alveolar arch on the major and minor segments (R/r
ratio) by using the following formula: R/r ratio = the curvatures of the
appropriate circle of the upper alveolar arch on the major segment (R)/the
curvatures of the appropriate circle of the upper alveolar arch on the minor
segment (r). The R/r ratios at the time of lip and palatal repair will be compared
between the NAM and non-NAM groups.
RCT- (Phase II)
2.2. Quantitative nasal anthropometric analysis on photographs (Photogrammetry):
Comparing the affected and unaffected sides after surgery by direct digitization
process of the nasal morphology after surgical repair through quantifying the
geometry of the nasal cavity.
Digital photographs will be taken after the primary surgical repair for the infants
head to obtain submento-vertical views including the recommended landmarks.
Landmarks, constructs and reference lines anthropometric landmarks on face and nose
will be selected as extracted from the geometrical condition of the discriminated
nostril coordinates.
The algorithm aims to simplify the process of extracting Area Of Interest (AOI), in
our case is the face, extracting Region(s) Of Interest (ROI), in our case are the
eyes, nose, etc.
There are two main steps:
I- Pre-processing steps:
1. This is about identifying the AOI through Image threshold where face
boundaries are identified.
2. Within AOI, facial features are identified such as eyes to be used as
reference points to define the horizontal baseline.
3. Vertical symmetry axis is identified as the perpendicular line on horizontal
baseline passing through the mid point between eyes.
II- Processing steps:
4. Get nose data (ROI).
5. Mirror the normal side.
6. Mark the difference between the normal and actual state.
7. Calculate statistics and geometrical parameters.
