Randomized Controlled Trial of Voice on Children With Vocal Nodules

Voice disorders place over five million school-aged children at increased risk for inferior
school performance, dysfunctional social development, and higher participation in criminal
activities. The lesions most commonly associated with pediatric vocal dysfunction are
reported to be vocal fold nodules, which are present in up to 21% of the general pediatric
population and are associated with behavioral problems and inferior quality of life. Voice
therapy with a speech-language pathologist is recommended by 95% of otolaryngologists for
management of vocal fold nodules. When implemented, this voice therapy requires significant
time investment and typically results in regular absence from the classroom over a period of
1-3 months or longer, depending on the protocol and the setting. Regular absence from school
has been shown to place children at risk for poorer scholastic performance but the benefits
of this voice therapy have yet to be demonstrated in any rigorous prospective, controlled
trial. Thus, the most widely used treatment for the most common lesion associated with
pediatric voice disorders has not been rigorously tested in a randomized controlled trial to
determine whether it may have benefits.

A randomized clinical trial addressing whether voice therapy improves voice-related quality
of life for children with apparent vocal fold nodules is a logical step toward developing an
evidence-based treatment plan to optimize outcomes for this sizable population of at-risk
children. There are currently no well-powered, prospective, controlled studies which compare
voice therapy versus control in children who present with apparent nodules. Our goal is to
remedy this deficiency through testing of the following primary null hypothesis: There is no
difference in the change in PVRQOL scores after 3 months of treatment with voice therapy
versus office instructions.

Inclusion criteria

1. Eligibility is contingent on the presence of apparent vocal fold nodules, which are
defined as bilateral, localized, benign, superficial growths with protrusion on the
medial surface of the true vocal folds at the junction of their anterior and middle
thirds. This examination is based on video-stroboscopic examination, or, in rare
cases, on operative microsuspension laryngoscopy. In addition, strict exclusion
criteria are applied toward excluding masses that are not nodules. Defining
characteristics for these inclusion criteria are based upon the evaluations of three
senior otolaryngologists of each participant's exam. Children evaluated by the senior
otolaryngologist at each institution suspected to have vocal fold nodules are
candidates for inclusion to this study. Patient de-identified images of the
stroboscopy are reviewed by each of the other two laryngologists; only those children
with confirmed vocal fold nodules by the all three senior otolaryngologists will be
considered for entry into this study.

2. Children 6 to10 years of age will be enrolled. The rationale for this age range was
previously noted. In brief, children in this age range (a) have similar educational
and social exposures; (b) will likely not yet encounter pubertal changes affecting
the larynx; and (c) are relatively cognitively homogeneous. Moreover, children in
this age range have the ability to cooperate with voice therapy and have also been
shown to be tolerant of stroboscopic examination. Finally, the voice therapy regimen
in this protocol has been shown to be clinically effective for many children in this
age range.

3. Voice-related quality of life must be affected to the extent that baseline PVRQOL
scores are <87.5 (on a scale of the worst, 0, to the best, 100) at the time of entry
into the trial. Based on previously published data, this subset of scores will be
clearly distinct from scores in children with normal voices. In addition, scores
<87.5 represent worse than average scores among children diagnosed with vocal fold
nodules.

4. Dysphonia duration prior to randomization must be at least 12 weeks, in order to
ensure that vocal dysfunction is chronic in nature.

5. Hearing in better ear of 35 dB or better.

6. Agreement by informed consent from the parents and informed assent from the child
participant with anticipated commitment to compliance throughout the follow up period
of 3 months is necessary for enrollment which includes time commitment of up to 3
hours per week to therapy sessions and homework.

7. Vocal fold nodules are a pathology that predominantly affects males. A number of
studies and the databases utilized to track this pathology at the clinical sites
indicate that the male: female ratio is approximately 7:3. Given this background, the
enrollment plan for the current investigation will seek to have a 30% female
representation of the patients enrolled in this study to ensure appropriate gender
representation. Additionally, patients with a diagnosis of pediatric vocal fold
nodules predominantly are found in Caucasian populations. However, in accordance with
the National Institute of Health Revitalization Act of 1993 the inclusion of
minorities in this proposal will be targeted to the representation of minorities in
the greater Boston, Philadelphia and Milwaukee metropolitan regions.

Exclusion criteria

1. Children with non-standard nodules or masses that are not unequivocally nodules are
excluded, including those with irregular epithelium, concern for malignancy requiring
biopsy, rapid growth pattern, airway obstruction requiring urgent or operative
intervention, and prior laryngeal surgery. Furthermore, since there are several
lesions that can present as bilateral true vocal fold masses (such as unilateral
cysts or polyps with contralateral fibrovascular reaction, contact granulomas, and
Reinke's edema), masses with the following characteristics will be excluded: a)
yellow or blue color suggestive of a mucous- or fluid-filled component, b) pink
friable lesions at the posterior aspect of the true vocal folds, c) watery edematous
expansion without a distinct protrusive mass. Defining characteristics for these
exclusion criteria are determined and corroborated by the evaluations of three senior
otolaryngologists of each participant's videostroboscopic exam. This examination is
based on video-stroboscopy, or, in rare cases, on operative microsuspension
laryngoscopy. The video images will be placed on a password-protected server to which
all three senior investigators will have access; these video images will not contain
any patient identifying information but rather a study number that will be assigned
to each participant. In addition, strict inclusion criteria are applied toward
excluding masses that are not nodules.

2. Children who have previously received any form of speech therapy targeting voice
and/or resonance with the exception of articulation or speech therapy.

3. Children for whom voice therapy protocols will be problematic are excluded:
developmental delay, cognitive disorder, behavioral disorder, neurologic disorder,
articulation disorder, phonological disorder, language disorder, expressive and/or
receptive language delay, specific language impairment, central auditory processing
disorder, fluency disorder, prior knowledge of voice therapy principles through
previous interventions (with the exception of articulation or speech therapy), and
inability to commit to at least 12 weeks of therapy as determined and evaluated by
the treating speech language pathologist and confirmed by consensus of all three PIs.

4. Children whose caregivers cannot complete the primary endpoint are excluded:
non-English speaking as the PVRQOL instrument is administered in English, and those
unable to commit to the 3-month treatment and follow-up schedule.

5. Children whose caregivers are not willing to commit up to 3 hours per week to vocal
therapy including therapy sessions and homework for up to 12 weeks.

6. Children who cannot tolerate a conscious video-stroboscopic examination and whose
parents feel that the diagnostic information gained by a planned examination under
anesthesia is not valuable for the severity of presenting symptoms are excluded.

7. Children with significant confounders of voice-related quality of life are excluded:
vocal fold paralysis, neurologic disorder of the larynx (dystonias, tics, tremors,
etc), ongoing acute upper respiratory tract infection (defined by at least 2 of the
following: sneezing, coughing, nasal congestion, runny nose, or temperature greater
than 100.4° F (38.0° C), and untreated or unsuccessfully treated allergic
rhinitis/post nasal drip.