Optimizing the Social Engagement System in Prader-Willi Syndrome: Insights From the Polyvagal Theory

• ClinicalTrials.gov Identifier: NCT03101826
• Recruitment Status: Terminated
• First Posted: April 5, 2017
• Last Update Posted: April 3, 2023
• Sponsor: Indiana University
• Collaborator: Latham Centers
• Information provided by (Responsible Party): Stephen Porges, Indiana University

Study Description

Brief Summary:

The Polyvagal Theory focuses on how function and structure changed in the vertebrate autonomic nervous system during evolution. The theory is named for the vagus, a major cranial nerve that regulates bodily state. As a function of evolution, humans and other mammals have a "new" vagal pathway that links the regulation of bodily state to the control of the muscles of the face and head including the middle ear muscles. These pathways regulating body state, facial gesture, listening (i.e., middle ear muscles), and vocal communication collectively function as a Social Engagement System (SES). Because the Social Engagement System is an integrated system, interventions influencing one component of this system (e.g., middle ear muscles) may impact on the other components.

Individuals with Prader-Willi Syndrome (PWS) exhibit many behaviors that are consistent with a compromised Social Engagement System. Atypical function of the Social Engagement System results in problems associated with state regulation (e.g., impulsivity, tantrums, and difficulty with change in routine), ingestion (e.g., difficulties in sucking at birth, hyperphagia), coordination of suck/swallow/breathe, intonation of vocalizations, auditory processing and hypersensitivity, and socialization. We propose to confirm that several features of the behavioral phenotype of PWS may be explained within the context of a dysfunctional SES (Specific Aim I), which may be partially rehabilitated via an intervention designed as a 'neural exercise' of the SES (Specific Aim II).

Specific Aims:

Aim I: To demonstrate that children with PWS have atypical regulation of the SES. We hypothesize these effects will be manifested by dampened vagal regulation of the heart (low parasympathetic tone); poor middle ear muscle regulation resulting in auditory hypersensitivities and poor auditory processing; lack of voice intonation (prosody), and difficulties in accurately detecting the emotions of others.

Aim II: To demonstrate the effectiveness of the Listening Project Protocol (LPP) in decreasing the atypical features of the SES in adolescents with PWS. We hypothesize that individuals who complete the LPP will have improved vagal regulation of the heart, improved middle ear muscle regulation, increased voice intonation and improved ability to accurately detect the emotions of others.

Condition or disease	Intervention/treatment	Phase
Prader-Willi Syndrome	Behavioral: Listening Project Protocol	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All participants will receive the active (filtered music) intervention.
• Masking: None (Open Label)
• Masking Description: No masking.
• Primary Purpose: Basic Science
• Official Title: Optimizing the Social Engagement System in Prader-Willi Syndrome: Insights From the Polyvagal Theory
• Actual Study Start Date: November 1, 2017
• Actual Primary Completion Date: March 8, 2023
• Actual Study Completion Date: March 8, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Filtered Music Intervention; All participants will participate in pre-intervention assessments (6 months, 1 week prior) and post-intervention assessments (1 week, 1 month post). The Filtered Music Intervention (i.e., Listening Project Protocol) will last for 1 hour per day, for 5 consecutive days.

Behavioral: Listening Project Protocol; The filtered music intervention will consist of listening to computer-altered acoustic stimulation, designed to modulate the frequency band of vocal music passed to the participant. The frequency characteristics of the acoustic stimulation are selected to emphasize the relative importance of specific frequencies in conveying the information embedded in human speech Modulation of the acoustic energy within the frequencies of human voice, similar to an exaggerated vocal prosody, are hypothesized to recruit and modulate the neural regulation of the middle ear muscles and to functionally reduce sound hypersensitivities and improve auditory processing.; Other Name: Safe and Sound Protocol

Outcome Measures

Primary Outcome Measures :

1. Effect of Intervention on Autonomic regulation [ Time Frame: Change from 1 week pre-intervention RSA to 1 month post-intervention ]
   Respiratory sinus arrhythmia (RSA)

Secondary Outcome Measures :

1. Effect of Intervention on Heart period [ Time Frame: Change from 1 week pre-intervention heart period to 1 month post-intervention ]
   heart period
2. Effect of Intervention on Auditory processing [ Time Frame: Change from 1 week pre-intervention Filtered Words to 1 month post-intervention ]
   Filtered Words subtest of SCAN
3. Effect of Intervention on Auditory processing [ Time Frame: Change from 1 week pre-intervention Competing Words to 1 month post-intervention ]
   Competing Words subtest of SCAN
4. Effect of Intervention on Sensory Sensitivities [ Time Frame: Change from 1 week pre-intervention BBC Sensory Scales to 1 month post-intervention ]
   BBC Sensory Scales (questionnaire)
5. Effect of Intervention on Latency to Affect recognition [ Time Frame: Change from 1 week pre-intervention DARE (latency) to 1 month post-intervention ]
   Dynamic Affect Recognition Evaluation (DARE) - latency
6. Effect of Intervention on Accuracy of Affect recognition [ Time Frame: Change from 1 week pre-intervention DARE (accuracy) to 1 month post-intervention ]
   Dynamic Affect Recognition Evaluation (DARE) - accuracy
7. Effect of Intervention on Prosody [ Time Frame: Change from 1 week pre-intervention Prosody to 1 month post-intervention ]
   Analyses of vocal recordings
8. Effect of Intervention on Disruptive Behavior [ Time Frame: Change from 1 week pre-intervention DBC to 1 month post-intervention ]
   Developmental Behavior Checklist (DBC) (questionnaire)
9. Effect of Intervention on Social behavior [ Time Frame: Change from 1 week post-intervention LPP to 1 month post-intervention ]
   Listening Project Parent (LPP) Questionnaire
10. Effect of Intervention on Oxytocin [ Time Frame: Change from 1 week pre-intervention oxytocin to 1 month post-intervention ]
    oxytocin levels derived from salivary sample
11. Effect of Intervention on Vasopressin [ Time Frame: Change from 1 week pre-intervention vasopressin to 1 month post-intervention ]
    vasopressin levels derived from salivary sample

Other Outcome Measures:

1. Stability of Autonomic regulation [ Time Frame: Change from 6 months pre-intervention RSA to 1 week pre-intervention ]
   Respiratory sinus arrhythmia (RSA)
2. Immediate effects of intervention on Autonomic regulation [ Time Frame: Change from 1 week pre-intervention RSA to 1 week post-intervention ]
   Respiratory sinus arrhythmia (RSA)
3. Short-term effects of intervention on Autonomic regulation [ Time Frame: Change from 1 week post-intervention RSA to 1 month post-intervention ]
   Respiratory sinus arrhythmia (RSA)
4. Stability of Heart period [ Time Frame: Change from 6 months pre-intervention heart period to 1 week pre-intervention ]
   heart period
5. Immediate effects of intervention on Heart period [ Time Frame: Change from 1 week pre-intervention heart period to 1 week post-intervention ]
   heart period
6. Short-term effects of intervention on Heart period [ Time Frame: Change from 1 week post-intervention heart period to 1 month post-intervention ]
   heart period
7. Stability of Auditory processing [ Time Frame: Change from 6 months pre-intervention Filtered Words to 1 week pre-intervention ]
   Filtered Words subtest of SCAN
8. Immediate effects of intervention on Auditory processing [ Time Frame: Change from 1 week pre-intervention Filtered Words to 1 week post-intervention ]
   Filtered Words subtest of SCAN
9. Short-term effects of intervention on Auditory processing [ Time Frame: Change from 1 week post-intervention Filtered Words to 1 month post-intervention ]
   Filtered Words subtest of SCAN
10. Stability of Auditory processing [ Time Frame: Change from 6 months pre-intervention Competing Words to 1 week pre-intervention ]
    Competing Words subtest of SCAN
11. Immediate effects of intervention on Auditory processing [ Time Frame: Change from 1 week pre-intervention Competing Words to 1 week post-intervention ]
    Competing Words subtest of SCAN
12. Short-term effects of intervention on Auditory processing [ Time Frame: Change from 1 week post-intervention Competing Words to 1 month post-intervention ]
    Competing Words subtest of SCAN
13. Stability of Sensory Sensitivities [ Time Frame: Change from 6 months pre-intervention BBC Sensory Scales to 1 week pre-intervention ]
    BBC Sensory Scales (questionnaire)
14. Stability of Latency to Affect recognition [ Time Frame: Change from 6 months pre-intervention DARE latency to 1 week pre-intervention ]
    Dynamic Affect Recognition Evaluation (DARE) - latency
15. Immediate effects of intervention on Latency to Affect recognition [ Time Frame: Change from 1 week pre-intervention DARE latency to 1 week post-intervention ]
    Dynamic Affect Recognition Evaluation (DARE) - latency
16. Short-term effects of intervention on Latency to Affect recognition [ Time Frame: Change from 1 week post-intervention DARE latency to 1 month post-intervention ]
    Dynamic Affect Recognition Evaluation (DARE) - latency
17. Stability of Accuracy of Affect recognition [ Time Frame: Change from 6 months pre-intervention DARE accuracy to 1 week pre-intervention ]
    Dynamic Affect Recognition Evaluation (DARE) - accuracy
18. Immediate effects of intervention on Accuracy of Affect recognition [ Time Frame: Change from 1 week pre-intervention DARE accuracy to 1 week post-intervention ]
    Dynamic Affect Recognition Evaluation (DARE) - accuracy
19. Short-term effects of intervention on Accuracy of Affect recognition [ Time Frame: Change from 1 week post-intervention DARE accuracy to 1 month post-intervention ]
    Dynamic Affect Recognition Evaluation (DARE) - accuracy
20. Stability of Prosody [ Time Frame: Change from 6 months pre-intervention prosody to 1 week pre-intervention ]
    Analyses of vocal recordings
21. Immediate effects of intervention on Prosody [ Time Frame: Change from 1 week pre-intervention prosody to 1 week post-intervention ]
    Analyses of vocal recordings
22. Short-term effects of intervention on Prosody [ Time Frame: Change from 1 week post-intervention prosody to 1 month post-intervention ]
    Analyses of vocal recordings
23. Stability of Disruptive behavior [ Time Frame: Change from 6 months pre-intervention DBC to 1 week pre-intervention ]
    Developmental Behavior Checklist (DBC) (questionnaire)
24. Immediate effects of intervention on Disruptive behavior [ Time Frame: Change from 1 week pre-intervention DBC to 1 week post-intervention ]
    Developmental Behavior Checklist (DBC) (questionnaire)
25. Short-term effects of intervention on Disruptive behavior [ Time Frame: Change from 1 week post-intervention DBC to 1 month post-intervention ]
    Developmental Behavior Checklist (DBC) (questionnaire)
26. Stability of Oxytocin [ Time Frame: Change from 6 months pre-intervention oxytocin to 1 week pre-intervention ]
    oxytocin levels derived from salivary sample
27. Stability of Vasopressin [ Time Frame: Change from 6 months pre-intervention vasopressin to 1 week pre-intervention ]
    vasopressin levels derived from salivary sample

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participants must be current residents at Latham Centers (LC) School in Brewster MA
2. Participants must meet criteria for Prader-Willi Syndrome
3. Participants must be between ages 13 - 25 years
4. Participants must have normal hearing
5. Participants must have normal vision (or corrected vision)

Exclusion Criteria:

1. Individuals with current (or a history of) heart disease
2. Individuals who are hearing-impaired
3. Individuals who are being treated for seizure disorder
4. Individuals who do not read/speak English
5. Individuals who are sight-impaired without correction

Contacts and Locations

Locations

United States, Massachusetts

Latham Centers School

Brewster, Massachusetts, United States, 02631

Sponsors and Collaborators

Indiana University

Latham Centers

Investigators

• Principal Investigator: Stephen W Porges, PhD; Indiana University/Kinsey Institute

More Information

Publications:

Bal E, Harden E, Lamb D, Van Hecke AV, Denver JW, Porges SW. Emotion recognition in children with autism spectrum disorders: relations to eye gaze and autonomic state. J Autism Dev Disord. 2010 Mar;40(3):358-70. doi: 10.1007/s10803-009-0884-3.

Borg E, Counter SA. The middle-ear muscles. Sci Am. 1989 Aug;261(2):74-80. doi: 10.1038/scientificamerican0889-74. No abstract available.

Lewis GF, Furman SA, McCool MF, Porges SW. Statistical strategies to quantify respiratory sinus arrhythmia: are commonly used metrics equivalent? Biol Psychol. 2012 Feb;89(2):349-64. doi: 10.1016/j.biopsycho.2011.11.009. Epub 2011 Dec 3.

Porges SW. The polyvagal theory: phylogenetic substrates of a social nervous system. Int J Psychophysiol. 2001 Oct;42(2):123-46. doi: 10.1016/s0167-8760(01)00162-3.

Porges SW, Macellaio M, Stanfill SD, McCue K, Lewis GF, Harden ER, Handelman M, Denver J, Bazhenova OV, Heilman KJ. Respiratory sinus arrhythmia and auditory processing in autism: modifiable deficits of an integrated social engagement system? Int J Psychophysiol. 2013 Jun;88(3):261-70. doi: 10.1016/j.ijpsycho.2012.11.009. Epub 2012 Nov 29.

Porges SW, Bazhenova OV, Bal E, Carlson N, Sorokin Y, Heilman KJ, Cook EH, Lewis GF. Reducing auditory hypersensitivities in autistic spectrum disorder: preliminary findings evaluating the listening project protocol. Front Pediatr. 2014 Aug 1;2:80. doi: 10.3389/fped.2014.00080. eCollection 2014.

• Responsible Party: Stephen Porges, Distinguished University Scientist, Indiana University
• ClinicalTrials.gov Identifier: NCT03101826
• Other Study ID Numbers: 1609337519
• First Posted: April 5, 2017
• Last Update Posted: April 3, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stephen Porges, Indiana University:

Polyvagal Theory; Respiratory Sinus Arrhythmia; Heart rate; Social Behavior; Arginine Vasopressin; Dichotic Listening Tests; Oxytocin; Hyperacusis; Affect; Auditory perception; Sound spectrography

Additional relevant MeSH terms:

Prader-Willi Syndrome; Syndrome; Disease; Pathologic Processes; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Obesity; Overweight; Overnutrition; Nutrition Disorders