Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05560750 |
| Other study ID # |
83/2022 |
| Secondary ID |
2022-001546-37 |
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 3, 2022 |
| Est. completion date |
December 31, 2028 |
Study information
| Verified date |
January 2024 |
| Source |
University of Oulu |
| Contact |
Outi Aikio, MD, PhD |
| Phone |
+358 8 3155810 |
| Email |
outi.aikio[@]ppshp.fi |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Oral cavity's structural variations are involved in the successful breastfeeding of the
newborn infants. The tongue-tie has been shown to cause breastfeeding problems. This project
investigates the oral structural properties of the newborn infants and the efficacy and
safety of their treatment options in breastfeeding problems. The project includes two
studies: 1. A prospective follow-up study that investigates the epidemiology and associations
between oral structures and breastfeeding problems in term and preterm infants; 2. A
randomised, controlled study that investigates the efficacy and safety of tongue-tie
treatments. Follow-up visits are planned two to three months, one year, and five years after
randomisation along with a 6 months' e-questionnaire for all study patients. The study
provides information at the population level.
Description:
Part 3 of the LINNE project: Efficacy and safety of neonatal tongue-tie therapies: a
controlled, randomised, clinical trial
1 Aim, hypotheses and objectives
Present trial investigates the effectiveness and safety of conservative and surgical
treatments of tongue-tie in treatment of neonatal feeding difficulties. The neonatal
participants have been diagnosed an anatomical and functional tongue-tie that interferes
feeding in the observational study (Project parts 1-2).
Hypotheses
1. A tongue-tie release procedure, frenotomy, indicated by the study tongue-tie criteria,
is effective and safe
2. The mother's breastfeeding experience and the parents' satisfaction improve with
adequate treatment of the newborn
3. No long-term adverse effects will be detected.
Aims
1. To investigate the efficacy and safety of operative versus conservative treatment of a
tongue-tie diagnosed with the study criteria
2. To study the mother's breastfeeding experience and parents' satisfaction to different
treatment approaches.
3. To conduct the long-term follow-up of the treatments.
2 Study design
A randomised, controlled, blinded, single-centre, clinical trial. Study arms:
1. Open study treatment (index therapy) is the frenotomy performed under local anaesthesia
or general anaesthesia, i.e., an operative release of the tongue-tie immediately after
its detection.
Description of the procedure: During the excision of the tongue-tie, the parent is
sitting in a chair with the infant in his/her lap. The child may be lying on the
treatment table as well. In both cases, an assistant supports the child's head.
Anaesthesia is conducted with medical cream (lidocaine 25 mg/ml and prilocaine 25 mg/ml)
that is applied into the floor of the mouth on both sides of the lingual frenulum, up to
1 ml, approximately for 30 sec - 1 min. The anaesthetic then is removed by sweeping by a
bandage. The tongue is elevated with a grooved director and the lingual frenulum is cut
with scissors to free the tip of the tongue. The release is targeted to the mucosal and
connective tissue parts of the lingual frenulum, the muscle fibres will not be cut. It
is a quick procedure; 20 minutes will be reserved for the appointment.
The procedure may result in minor bleeding which can be controlled by compressing it
with a bandage moistened with lidocaine-adrenal solution, if necessary. The solution is
prepared by mixing 20 ml of Lidocaine 20 mg/ml, and 1 ml of Adrenalin 1 mg/ml. The
solution is a generally used topical anaesthetic in otorhinolaryngological (ORL)
procedures. Normal bleeding from the procedure usually lasts a few minutes, up to 10
minutes. Due to bleeding, corrective procedures (diathermy) are needed extremely rarely.
Afterwards, some bloody stains in the baby pukes are possible and parents will be
informed about it.
As after-care, parent will be guided a physiotherapy of the surgical area to prevent
scarring (Annex 3: hospital guidelines). In addition, if necessary, parents are advised
to give paracetamol mixture 24mg/ml by the weight-based dosage (15mg/kg) up to three
times a day for couple days if the child seems to have pain or discomfort. A control
visit takes place one month after the procedure.
2. Conservative treatment includes a sensitive oral physiotherapy aiming to stretch the
tongue-tie (Annex 4 and internet video (YouTube)). Treatment will continue up to 4
weeks, unless the Study infant follow-up guideline for urgent treatment criteria, given
to the parents at randomisation, would be earlier met (Annex 5). According to the
guidelines, the parents may contact investigators any time when necessary. The need for
operative treatment is re-evaluated at the follow-up visit after the physiotherapy
period, or at an earlier appointment on demand.
3. The follow-up group (no-treatment) receive the appointment date for the procedure at one
month after randomisation. However, if the Study infant follow-up guideline criteria
(Annex 5) would be met prior to the date given, parents may contact investigators and
the appointment would take place earlier.
A two to three minutes video recording of the infants' feeding is documented using the study
mobile phone.
The main purpose of the feasibility study is to assess the validity and practicality of the
previously unused research components that are essential and unique to the present trial.
These include e.g. the study anatomical-functional scoring, oral physiotherapy, and the
blinding method of the parents. According to the preliminary plan, the trial will be
conducted using the same formulations as the feasibility pilot, but some details of the final
design, as well as the sample size estimation, will be checked upon the feasibility study
results.
3 Sample size
Feasibility study:
According to a previous study, the harm caused by a tongue-tie had been disappeared in 92% of
the operated children three months after the procedure. In the group of non-operated control
patients, 47% reported that the harm disappeared without the procedure. According to the null
hypothesis of this feasibility study, the groups do not differ, i.e., the treatments have no
effect on breastfeeding success. With 80% power and 5% alpha error, the required sample size
is 15 infants/group. Due to the randomisation to three groups, n=48 is needed, resulting in a
group size of n=16.
Randomised clinical trial (RCT):
In a previous six-year follow-up study of Dept. of Otorhinolaryngology, Oulu University
Hospital (2013-2018), 365 tongue-tie diagnoses were done, mean 61/year. The number of
operative treatments was 334, i.e., 56/year. For the final sample size calculation, the
change in the primary outcome required will be checked upon the feasibility pilot. An
educated guess is approximately 300 infants (100/group).
4 Blinding and randomization
The study physician will discuss with the parents and request the written informed consent.
An assigned randomisation executor, beyond the study group, will conduct the computed
randomisation of the trial code numbers prior to the beginning of the trial. The codes will
be written upon the opaque envelopes, containing information of the study therapy group in
question.
After the informed consent, the infant will be assigned the next free trial code from the
list. The investigator opens the envelope marked by the code number, in which the treatment
group information is placed. The study nurse organizes the follow-up visits and guides with
the treatment and follow-up instructions.
5 Follow-up protocols
Patients will be invited to an evaluation visit by a speech therapist at the age of 2-3
months. The research will be carried out at Oulu University Hospital. A speech therapist,
specialising in neonatal feeding, will be blinded to the patient's treatment group. Infant
sucking pattern, interruptions in sucking, irritability during breastfeeding, possible
flatulence, and possible breastfeeding problems are evaluated.
The trial patients are invited to outpatient clinic control visits at the age of 1 and 5
years.
At the age of one year (12 ± 2 mo) control visits, eating patterns (sucking, swallowing,
biting, chewing, drooling, eating solid foods, cleaning the mouth by tongue, resting position
of the tongue, licking, sweeping around the lips by the tongue), presence of mouth breathing,
and dentition development are assessed. The examination may be videotaped, and if necessary,
with a separate parental permission, specifically if the child has an eating or speech
defect. Control visits take place at the Oulu University Hospital ORL-department by study
physicians.
At the age of five years (exclusion criteria: diagnoses affecting speech and language
development), the production of sounds requiring tongue tip raising ([t, d, n, l, s, r],
including a total of 30 words, 5 per sound) is assessed by the child naming them from
pictures. Should the naming be not successful, the child will be asked to repeat. The
discussion will take only a short time, or the child will be asked to tell. The visit will be
videotaped. A logopedic assessment group will evaluate the abnormalities of articulation
(abnormal/not) and intelligibility of the speech (VAS scale), and by using a four-point
Likert scale whether the possible articulation errors affect the intelligibility of the
speech. In addition, the parents will be asked about the child's eating habits and possible
problems.
6 Data management
Patient data as well as study videotapes will be recorded to the electronic research
database, the study hospital's M-drive, that can be accessed only by study team members. The
data of the children participating in the trial is collected from the study files and e-mail
questionnaires. Information necessary for the study is stored in the database. All paper
documents are kept in the closed office of the principal investigator until the official
storage period of the research archive has ended. A self-assessment of the security risks of
the study data has been stated for parental access upon demand.
Only the study personnel know the identity and other identifiable information of the study
patients, and they are all bounded by secrecy. All data are processed and coded in such a way
that individual information cannot be identified from the study results. An inspector
external to the study (monitor) has the right to revise the study documents if necessary.
7 Statistical methods
Special statistical program (IBM SPSS) will be used for statistical analyses. Continuous
variables will be analysed with a t-test or non-parametric tests, depending on the
distribution. Chi2 or Fisher's exact tests are used for the analysis of dichotomous
variables. Analyses of associations are performed with Pearson's, Spearman's or Kendall's
correlation coefficients and, if necessary, variance or regression analyses (Risk ratio, Odds
ratio, numbers needed to treat). Consistency between researchers is tested with the Kappa
coefficient. The results will be analysed according to the intention-to-treat principle. The
limit of statistical significance is set at p<0.05.
8 Study permits and practices
The trial authorization of the regional ethics committee has been applied and permitted.
Permission for the clinical study is being sought from the administrative management of Oulu
University Hospital.
The research will be conducted the principles of Good Clinical Practice (GCP). An external
monitor will be appointed for the study for the implementation of the study and the
fulfilment of the patients' rights.
The hospital patient insurance covers all the study patients. Patients will not be
compensated for participating in the trial, with the exception of normal parental
accompanying costs.
9 Quality and appropriateness of the premises and equipment of the trial sites
The Oulu University Hospital's Mother-Child Unit, Department of Otorhinolaryngology, Neonatal
Intensive Care Unit, Neonatal ward, and Faculty of Humanities, Research Unit of Logopedics,
are the study sites. The qualifications of the personnel of these units are appropriate for
the implementation of the research. The equipment of the tertiary-level hospital and the
emergency facilities are modern and appropriate for study safety.
10 Timetable estimation
Prospective study will be launched during the fall of 2022. The recruitment will last for an
estimated three years, and the follow-up protocol will continue for another five years. The
first analyses and reporting of the results of the feasibility study will be done during
2023-2024.
11 Funding
The present project will be carried out using personal and project grants, applied from the
medical research foundations. The study represents an investigator-driven research and will
be executed without commercial funding. The project has no connections to the pharmaceutical
or any other commercial companies.
