Autonomic Dysfunction in Functional Dysphonia

Muscle Tension Dysphonia Clinical Trial

Official title:

Autonomic Dysfunction in Functional Dysphonia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06100601
• Other study ID #: BOF23/PDO/059
• Status: Recruiting
• Phase: N/A
• Start date: October 10, 2023
• Est. completion date: December 2026

Study information

• Verified date: October 2023
• Source: University Ghent
• Contact: Iris Meerschman, PhD
• Phone: +32499294636
• Email: iris.meerschman[@]ugent.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The first objective of this research project is to compare the occurrence and frequency of symptoms and/or disorders related to autonomic dysfunction in patients with functional dysphonia with gender- and age-matched vocally healthy controls, using a case-control study.

The second objective is to compare the effects of a novel therapy based on autonomic nervous system regulation (i.e., ANS therapy: heart rate variability biofeedback), for functional dysphonia versus coventional voice therapy (CVT) alone or in combination with ANS regulation therapy (i.e., ANS therapy + CVT), using a longitudinal randomized controlled trial (RCT).

Description:

Background. Although psychological factors have been implicated in patients with functional dysphonia (FD), conventional treatment typically targets the aberrant voice symptoms exclusively. Yet, symptomatic/conventional voice therapy (CVT) is not always successful, and in view of the significant adverse quality of life (QoL) impact combined with the substantial financial burden on the healthcare system and society, research is needed to elucidate the underlying pathogenesis and psychophysiology of FD and improve treatment outcomes. Given that (1) the Vagus nerve not only innervates the larynx, but helps to regulate the autonomic nervous system (ANS), (2) autonomic dysfunction is well recognized in the fields of psychology and psychiatry, but remains relatively understudied in the area of voice disorders, and, (3) many of the psychological symptoms/features commonly observed in patients with FD may reflect ANS dysregulation, we intend to investigate ANS dysfunction as a potential psychophysiological mechanism underlying FD; and, to evaluate the comparative effectiveness of a novel therapy that aims to improve ANS regulation in patients with FD.

Objectives. The first objective of this research project is to compare the occurrence and frequency of symptoms and/or disorders related to autonomic dysfunction in patients with FD with gender- and age-matched vocally healthy controls, using a case-control study. The second objective is to compare the effects of a novel therapy based on ANS regulation (i.e., ANS therapy: heart rate variability biofeedback), for FD versus CVT alone or in combination with ANS regulation therapy (i.e., ANS therapy + CVT), using a longitudinal randomized controlled trial (RCT).

Methods. Case-control study: Autonomic (dys)function of patients with FD will be compared with gender- and age-matched vocally healthy controls, using both physiological measures (e.g. heart rate variability, skin conductance level) and psychological patient-reported outcome measures (PROMs, e.g. Neuroception of Psychological Safety Scale, Depression Anxiety and Stress Scale). RCT: The FD group will be randomly assigned to the innovative ANS therapy group, the CVT group or the ANS therapy + CVT group. All patients will receive 1 month of treatment with 20min of daily practice. Both the autonomic assessment and the voice assessment will be performed pretherapy, immediately after therapy and at 3 months follow-up by assessors blinded to group allocation and study phase.

Expected results. Higher occurrence of symptoms and/or disorders related to autonomic dysfunction are expected in patients with FD compared with vocally healthy controls. Physiological outcomes: Lower heart rate variability, lower cardiac pre-ejection period, higher respiration rate and higher skin conductance level are hypothesized in patients with FD compared with vocally healthy controls. Psychological PROMs: Higher self-report of feelings/symptoms related to autonomic dysfunction (e.g. perceived stress, anxiety) is expected in patients with FD compared with vocally healthy controls. Autonomic function is hypothesized to improve more after the ANS therapy and the ANS therapy + CVT compared with the CVT only. Voice function is expected to improve more after the ANS therapy + CVT compared with the ANS therapy and the CVT alone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Patients with functional dysphonia will be recruited from a treatment-seeking population consulting at the voice clinic of Ghent University Hospital. Inclusion criteria are all genders, all ethnicities, aged 18 - 60 years (to exclude voice-related changes due to puberty/mutation or aging/presbyphonia), diagnosed with FD by an experienced otorhinolaryngologist and SLP (defined by a voice disorder in the absence of organic or structural mucosal disease and/or neuropathology sufficient to explain the voice disturbance (Roy et al., 2003), as determined with strobovideolaryngoscopy and a multidimensional voice assessment). Exclusion criteria include: being diagnosed with an organic voice disorder, current participation in voice therapy, practice of breathing exercises including mediation and yoga, current participation in psychotherapy or physical rehabilitation, pharmacological treatment (i.e. antidepressants, antipsychotics, heart medication, antihypertensives, inhalers), previous phonosurgical interventions, lung diseases, endocrinologic diseases, metabolic diseases, cardiovascular diseases, neurologic diseases, nasal or ear diseases, pregnancy, asthma, smoking or drug consumption.

For the vocally healthy controls, inclusion criteria are all genders, all ethnicities, aged 18 - 60 years, and matched with the FD groups by age and gender. The same exclusion criteria as above apply, with the addition of: 'diagnosed with FD'.

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Dysphonia
• Functional Voice Disorder
• Hoarseness
• Muscle Tension Dysphonia
• Primary Dysautonomias
• Voice Disorders

Intervention

Behavioral:
• ANS regulation therapy
innovative intervention for functional dysphonia
• conventional voice therapy (CVT)
conventional voice therapy traditionally provided for functional dysphonia
• ANS regulation therapy + CVT
combination of ANS regulation therapy and CVT

Locations

Country	Name	City	State
Belgium	Department of Rehabilitation Sciences, Ghent University (Hospital)	Ghent	East-Flanders

Sponsors (3)

Lead Sponsor	Collaborator
University Ghent	Universiteit Antwerpen, University of Utah

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	heart rate variability (HRV)	Heart rate variability (HRV, in ms) is an autonomic index measuring the variation of the interval between consecutive heartbeats and is vagally regulated (PSA) (Thayer et al., 2009; Pizzoli et al., 2021; Singh Solorzano et al., 2022). It measures direct Vagus nerve activation potential on a cardiac level (Thayer & Lane, 2000; Sars, 2022). High HRV is associated with high vagal tone, whereas low HRV indicates ANS dysregulation with low vagal tone and SA prominence (Idrobo-Ávila et al., 2022). HRV will be determined at rest with electrocardiography using Kubios HRV analysis software (Tarvainen et al., 2002; 2014; Niskanen et al., 2004). Ag/AgCl surface electrodes will be positioned on the participant's chest in a modified lead II configuration.	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Primary	Dysphonia Severity Index (DSI)	The DSI is an objective multiparametric indices that quantifies voice quality (Wuyts et al., 2000)	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	Pre-ejection period	The pre-ejection period is the time between the onset of depolarization of the left ventricle and the opening of the aortic valves and will be calculated as a cardiovascular index of SA (Lozano et al., 2007)	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	Respiration rate	Respiration rate (in bpm) will be determined via thoracic impedance (De Geus et al., 1995). For each respiratory cycle, the total cycle time between the start of inspiration and the end of expiration will be extrapolated to a per-minute respiration rate	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	Skin conductance level	Skin conductance level (in µS) will measure the tonic electrodermal activity and reflects increased SA (Dawson et al., 2017).	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	The Neuroception of Psychological Safety Scale	The Neuroception of Psychological Safety Scale (NPSS; Morton et al., 2022) is a psychometrically valid measure determining psychological, relational and physiological safety. It consists of 29 items subdivided into 3 subscales: compassion (e.g. I felt caring), social engagement (e.g. I felt accepted by others) and body sensations (e.g. My body felt relaxed).	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	The Depression Anxiety and Stress Scale 21	The Depression Anxiety and Stress Scale 21 (DASS-21; Lovibond PF & Lovibond SH, 1995; Dutch Version: De Beurs et al., 2001) is a validated 21-item checklist covering 3 subscales measuring the emotional states of depression (e.g. I felt that I had nothing to look forward to), anxiety (e.g. I felt scared with any good reason) and stress (e.g. I found myself getting agitated).	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	The Posttraumatic Stress Disorder Checklist for DSM-5	The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5; Weathers et al., 2013; Dutch version: Boeschoten et al., 2014; De Beurs et al., 2020) is a validated 20-item checklist that assesses the DSM-5 symptoms of PTSD. It exists of 4 clusters: re-experiencing (e.g. Repeated, disturbing dreams of the stressful experience), avoidance (e.g. Avoiding memories, thoughts, or feelings related to the stressful experience), numbing (e.g. Loss of interest in activities that you used to enjoy), and arousal factors (e.g. Irritable behavior, angry outbursts, or acting aggressively).	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	The short version of the Self Regulation Questionnaire	The short version of the Self Regulation Questionnaire (Brown & Miller, 1999; Carey et al., 2004; Neal & Carey, 2005) is a 31-item self-report measure of the ability to self-regulate one's behavior (e.g. Once I have a goal, I can usually plan how to reach it, I have a lot of willpower).	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	The Pittsburgh Sleep Quality Index	The Pittsburgh Sleep Quality Index (Dutch Version: Buysse et al., 1989) is a validated 19-item index assessing overall sleep quality. It consists of 7 subscales: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction.	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	Laryngeal function	A flexible strobovideolaryngoscopy will be performed by an experienced otorhinolaryngologist to visualize the laryngeal function and (supra)glottic activity. The video samples will be evaluated randomly and blindly by a specialized otorhinolaryngologists and SLP to assure interrater reliability; 15% of the samples will be randomly repeated to assess intrarater reliability. The Voice-Vibratory Assessment with Laryngeal Imaging (VALI) rating form (Poburka et al., 2017) will be used for these evaluations.	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	Acoustic Voice Quality Index (AVQI)	An instrumental voice assessment will be performed by an experienced SLP, different from the therapist. Acoustic measures will be obtained by the Computerized Speech Lab (KayPENTAX, Montvale, NY) and the software program Praat (Boersma & Weenink, 2013). A Shure SM-48 and an AKG Lyra microphone will be used. Two objective multiparametric indices will quantify voice quality: the DSI (Wuyts et al., 2000) and the AVQI (Maryn et al., 2010).	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	Consensus Auditory Perceptual Evaluation of Voice	An auditory-perceptual (subjective) voice evaluation will be performed using the Consensus Auditory Perceptual Evaluation of Voice (Kempster et al., 2009). Speech samples (sustained vowel and continuous speech) will be evaluated randomly and blindly by 2 experienced SLPs to assure interrater reliability; 15% of the samples will be randomly repeated to assess intrarater reliability.	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up
Secondary	voice-related patient-reported outcome measures	The Voice Handicap Index (Jacobson et al., 1997; Dutch version: De Bodt et al., 2000), the Vocal Tract Discomfort Scale (Mathieson et al., 2009; Dutch version: Luyten et al., 2016) and the Vocal Fatigue Index (Nanjundeswaran et al., 2015) will be administered to evaluate the psychosocial impact, vocal tract discomfort and vocal fatigue associated with dysphonia.	baseline (before the intervention), 1 months (after the intervention), 3 months follow-up