Effect of Semi-occluded Vocal Tract Therapy on the Phonation of Children With Vocal Fold Nodules.
Phase: NA
Conditions: Voice Disorders in Children, Vocal Nodules in Children, Hoarseness, Dysphonia
Sponsor: University Hospital, Ghent

 
 
 
Effect of Semi-occluded Vocal Tract 
Therapy on the Phonation of Children 
With Vocal Fold Nodules 
 
 
NCT05878197 
 
22/05/2024 
 

Study protocol 
This study was approved by the Ethics Committee of Ghent University Hospital 
(registration number: B670201936069) and has been registered on ClinicalTrials.gov. The 
consolidated standards of reporting trials (CONSORT) non-pharmacologic treatment 
interventions (NPT) checklist were used to report the trial specifications (Boutron et al., 
2017). Written informed consent was obtained from a parent of each participant. 
 
Participants 
Children between six and 12 years old (primary school) with VFNs were eligible to 
participate in this study. Participants were recruited between October 2019 and January 
2023 during their consultations at the voice unit of Ghent University Hospital, through 
flyers in other hospital departments, through social media, or by referral from voice 
therapists who were informed about this project. All participants were diagnosed with 
VFNs by an otorhinolarygologist with extensive experience in voice diagnostics (S.C.). 
This age group was chosen because these children can cooperate with voice therapy and 
tolerate videolaryngostroboscopy. Exclusion criteria were a history of phonosurgery, 
nasal or ear diseases, neurological disorders, and parent-reported pubertal voice 
changes. 
 
Design 
A randomized controlled study design was used. Participants were assigned to one of the 
three study arms (experimental group “SP”, experimental group “RVT”, or the control 
group (CG) receiving indirect treatment), depending on their time of registration. The 
order in which the different voice treatments were organized was determined using a 
random number list. No changes in the methodology were made after trial 
commencement. 
 
Voice therapy 
In each study arm, a short-term, intensive, group therapy program was provided. All 
participants received 11 hours of voice therapy spread over four consecutive days (three 
hours on day 1-3 and two hours on day 4). Each group consisted of a minimum of two and 
a maximum of five children and was guided by one experienced voice therapist (I.M. or 
A.A.). All therapy sessions were provided at Ghent University Hospital. During the study 
period, participants were not allowed to attend external voice therapy. 
The content and hierarchical structure of the different study arms were kept as similar as 
possible, with the exception of the direct vocal techniques. In the CG, no direct technique 
was included. Offered therapy consisted of basic education of the vocal mechanism, 
normal vocal function, and VFNs, vocal hygiene recommendations, posture advice, and 
costo-abdominal breathing exercises. Participants in the experimental groups received 
the same counseling and breathing exercises, combined with the direct vocal technique 

SP or RVT. For SP, participants used a stainless-steel drinking straw with a diameter of 5 
mm and a length of 23 cm. In each study arm, vocal rest pauses and play activities 
(identical for the experimental groups) were provided. Since no direct vocal technique 
was practiced in the CG, more play activities were scheduled in which excessive or loud 
voice use was being monitored and limited. Home exercises were foreseen in each study 
arm. Parents were not present during therapy but were informed verbally and in writing 
about the content of the therapy sessions so they could supervise home exercises. 
 
Voice assessment 
A standardized and multidimensional voice assessment, based on the protocol of the 
European Laryngological Society (Dejonckere et al., 2003) and supplemented with the 
acoustic voice quality index (AVQI) (Maryn et al., 2010a), was performed one day before 
the start of voice therapy and immediately after the last voice therapy session. A 
standardized pretest anamnesis by means of a semi-structured interview (see Appendix 
H) was used to examine the demographic characteristics, therapy history, vocal 
complaints, and risk factors. The assessments were performed by eight voice therapists 
of the Center for Speech and Language Sciences (T.P., I.K., J.D., C.L., C.V.S., C.A., L.B., 
and E.D.) with experience in voice diagnostics in two acoustically treated rooms at Ghent 
University Hospital. The assessors were blinded to group allocation and participants 
were assessed by the same assessor pre- and posttherapy. Voice assessment consisted 
of the following parts: (a) laryngeal anatomy and function, (b) voice quality and vocal 
capacities, and c) psychosocial wellbeing. 
 
A. Laryngeal anatomy and function 
Flexible videolaryngostroboscopy was performed during pretest to determine whether 
VFNs were present and to describe the baseline laryngeal anatomy and function in detail. 
In order to avoid overloading the children, videolaryngostroboscopy was performed only 
pretherapy. It can be perceived as an invasive examination by (young) children, therefore 
it was considered unethical to perform it twice over a period of five days. Flexible 
videolaryngostroboscopy was carried out by an experienced otorhinolaryngologist (S.C., 
more than 25 years of experience in diagnosing voice disorders) or one of her assistants 
(C.D.V. and M.D.K.). Participants were examined in seated position with the head upright. 
They were asked to produce a sustained vowel [i] at habitual pitch and loudness, followed 
by a high-pitched [i] and a low-to-high glissando using [i]. Videolaryngostroboscopy was 
sometimes terminated early due to discomfort in the children, but recording the vowel [i] 
at normal pitch and loudness was the minimum requirement. Videolaryngostroboscopic 
video samples were evaluated using the Voice-Vibratory Assessment with Laryngeal 
Imaging (VALI) rating form (Poburka et al., 2017) and a grading scale for pediatric VFNs 
(Nuss et al., 2012; Shah et al., 2007). The video samples were provided with audio. An 
otorhinolaryngologist (S.C.) and voice therapist (I.K.) randomly and blindly evaluated all 
video samples. Both raters had experience with administering the VALI rating form, but 

not with the grading scale for pediatric VFNs. A half-hour training session was provided in 
which each parameter was clarified with the definition, a high-quality graphic, and two 
video examples. The raters first evaluated the video samples independently, followed by 
a consensus evaluation. 
 
B. Voice quality and vocal capacities 
The Dysphonia severity index (DSI) is a multiparametric index, consisting of a weighted 
combination of the maximum phonation time (MPT, in s), minimal intensity (Ilow, in dB), 
maximal frequency (fhigh, in Hz), and jitter (%) (Wuyts et al., 2000). MPT was determined 
by asking the children to sustain the vowel [a:] as long as possible with habitual pitch and 
loudness after maximum inspiration. Three measurements were performed in free field 
while participants were seated. Children received verbal encouragements to produce the 
longest possible vowel. Time was measured with a chronometer and the longest result 
was used for further analyses. The Ilow and fhigh were determined using the Voice Range 
Profile of the Computerized Speech Lab (CSL, model 4500, KayPENTAX, Montvale, NY) 
and a Shure SM-48 microphone, located at a distance of 15 cm from the mouth and 
angled at 45 degrees. Participants were successively asked to produce the vowel [a:] with 
minimal loudness and maximal pitch and they were given multiple attempts to achieve 
the best result. Each production was demonstrated by the assessors, who also verbally 
encouraged the children. Jitter % was obtained by the Multi-Dimensional Voice Program 
of the CSL and the same Shure SM-48 microphone. Participants were asked to count to 
three (an automatic sequence), followed by a sustained vowel [a:] with habitual pitch and 
loudness. A midvowel segment of three seconds registered with a sampling rate of 50 kHz 
was used for the analysis. The DSI is calculated using the following formula: 0.13 × MFT 
+ 0.0053 × fhigh - 0.26 × Ilow - 1.18 × jitter + 12.4 (Wuyts et al., 2000). The index value 
usually ranges between -5 and +5. A lower index value indicates poorer voice quality or, 
more generally, poorer vocal functioning (Awan & Ensslen, 2010). The threshold score 
that distinguishes a normophonic from a dysphonic voice is +1.6 in adults (Raes et al., 
2002). This threshold score was used since norm values for Dutch children are currently 
missing. 
 
The Acoustic Voice Quality Index (AVQI) is an objective, multiparameter approach to 
quantify dysphonia severity on the basis of a sustained vowel [a:] and continuous speech 
(Maryn et al., 2010a). The index consists of a weighted combination of six time-domain 
parameters [i.e., shimmer local (SL), shimmer local decibels (SLdB), and harmonics-to-
noise ratio (HNR)), frequency-domain parameters (i.e., general slope of the spectrum 
(slope) and tilt of the regression line through the spectrum (tilt)), and quefrency-domain 
parameters (i.e., smoothed cepstral peak prominence (CPPs)]. The formula of the AVQI 
is 2.571 (3.295 − 0.111 CPPs − 0.073 HNR − 0.213 SL + 2.789 SLdB − 0.032 slope + 0.077 
tilt). The index ranges from 0 to 10 and a higher index indicates poorer voice quality. The 
threshold score that distinguishes a normophonic voice from a dysphonic voice in Dutch 

adults is 2.95 (Maryn et al., 2010a). An Australian study suggested a threshold score of 
3.46 in the pediatric population, but norm values for Dutch children are missing 
(Reynolds et al., 2012). In order to calculate the AVQI, the participants were asked to 
produce a sustained vowel [a:] at normal pitch and loudness and to read the Dutch 
phonetically balanced text "Papa and Marloes” (Van de Weijer & Slis, 1991). A Samson 
C01U Pro microphone, located at a distance of 15 cm from the mouth, and the software 
program PRAAT were used (Boersma & Weenink). A midvowel segment of 3 seconds of 
the vowel [a:] and the first two sentences of the text were combined in an automated 
script to calculate the AVQI. It is known that a minimum signal-to-noise ratio (SNR) of 30 
dB is required to obtain acceptable perturbation measurements (Deliyski et al., 2005). 
For this reason, all participants with a pre- or posttest sample with an SNR less than 30 
dB were removed from the analyses of the AVQI. 
 
Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) was used for the auditory-
perceptual evaluation of the children’s voices (Kempster et al., 2009). This tool is 
designed to describe the severity of dysphonia by rating six parameters (overall severity, 
roughness, breathiness, strain, pitch, and loudness) on a visual-analog scale from 0 to 
100, where 0 is considered within normal limits. The tool was supplemented by two 
additional visual-analog scales to measure asthenia and instability (Meerschman et al., 
2022). Two experienced voice therapists (T.P. and E.D.) independently and blindly rated 
all the pseudonymized samples in a random order. 
Afterwards, they relistened to the samples together to compare their individual 
evaluations and to reach a consensus. The samples consisted of the sustained vowel [a:] 
and the full text "Papa and Marloes," which were also used to determine the AVQI. The 
raters were allowed to listen multiple times to the samples. Training was not provided 
because both raters had experience with administering the CAPE-V. A random selection 
of 15% of the samples was doubled to calculate the intra-rater reliability. For this study, 
the CAPE-V overall severity was selected as a primary outcome parameter. The analysis 
of the other CAPE-V parameters can be found in Appendix I. 
 
C. Psychosocial wellbeing 
Pediatric Voice Handicap Index (pVHI). A parent completed the Dutch version of the pVHI, 
which is a parent-proxy tool to gain insight into the physical, functional and emotional 
impact of the voice disorder on their child (Veder et al., 2017). The pVHI consists of 23 
items which are evaluated using a five-point Likert scale (0: never, 1: almost never, 2: 
sometimes; 3: almost always; 4: always). Total pVHI scores range from 0 to 92 with a 
higher score corresponding with a greater psychosocial impact. The same parent was 
asked to complete the questionnaire pre- and posttherapy. 
 

Statistical analysis plan 
The statistical analysis was performed using IBM SPSS Statistics 28 software (SPSS, Inc. 
Chicago, IL). The significance level was set at α = 0.05. One-way ANOVAs were used to 
check for statistically significant differences in continuous parameters (e.g., age) 
between the three study arms. Fisher’s exact tests were used for the comparison of 
categorical parameters (e.g., sex) between the three study arms. Pairwise comparisons 
with Bonferroni corrections (α < 0.016) were performed when a significant difference was 
found between the groups. The inter- and intra-rater reliability of the CAPE-V overall 
severity has been examined with two-way mixed ICCs and their 95% confidence 
intervals, type consistency, single-rating, and interpreted following the classification of 
Koo and Li (2016) ((ICC > 0.9 ‘excellent’; 0.9 ≥ ICC > 0.75 ‘good’; 0.75 ≥ ICC > 0.5 
‘moderate’; ICC ≤ 0.5 ‘poor’). The effects of voice therapy were evaluated using two 
complementary approaches. 
Firstly, a more traditional group-level analysis was conducted. Linear mixed models were 
used to compare groups over time on the primary outcome parameters, using the 
restricted maximum likelihood estimation and unstructured covariance type. Time, 
group, and time-by-group interaction were specified as fixed factors. A random intercept 
for participants was included and within-group effects of time were determined using 
pairwise comparisons. Unstandardized effect sizes were presented in the form of the 
estimated mean differences and 95% confidence intervals for the outcome variables. For 
the analysis of the AVQI, only participants in whom the SNR of the pretest and posttest 
voice samples was greater than or equal to 30 dB were selected (Deliyski et al., 2006). 
Secondly, an individual-level analysis was conducted for a thorough clinical 
interpretation of the study results, which is not possible based on group-level average 
intervention effects (Sand, 2022). This individual analysis examined for each participant 
whether outcome parameters changed to a relevant degree or remained unchanged. 
Previous literature was considered to determine the magnitude of this relevant degree of 
change. For the DSI and AVQI, the relevant degree of change within one patient was set 
at 2.49 (Hakkesteegt et al., 2008) and 0.54 (Barsties & Maryn, 2013), respectively. For the 
pVHI and CAPE-V overall severity, the relevant degrees of change were not yet 
determined. Therefore, it was opted to exclude these outcome parameters from the 
individual analysis. The results show for DSI and AVQI what percentage of participants 
improved to a relevant degree, remained unchanged or deteriorated to a relevant degree. 
Wilson 95% confidence intervals for proportions were calculated.