Clinical trial NCT02325128: Augmentation of Exposure Therapy for High Levels of Social Anxiety Using Post-exposure Naps
Official title: Augmentation of Exposure Therapy for High Levels of Social Anxiety Using Post-exposure Naps
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Social Anxiety Disorder
Sleep Laboratory
Keywords: social anxiety
exposure therapy
extinction
sleep-dependent memory consolidation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2014-12-24
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Investigators will examine whether post-exposure naps can be used to strengthen therapeutic extinction memories formed during exposure therapy for extreme social anxiety. Thirty-two individuals with high levels of social anxiety, evidenced by scores of 60 or greater on the Liebowitz Social Anxiety Scale, by self-report during a clinical interview and by demonstrated enhanced psychophysiological reactivity when imagining a socially stressful scenario, will be enrolled as one of four participants in one of eight successive offerings of a validated 5-session exposure-based group treatment for extreme social anxiety. The third and fourth sessions conclude with each participant delivering a speech on a topic individually chosen to elicit significant social anxiety. Following these sessions, participants will go to the sleep laboratory where two will be given a 2-hour sleep opportunity with polysomnographic (PSG) monitoring and two will be similarly instrumented but undergo 2 hours of monitored quiet wakefulness. Before and after treatment, participants will be individually assessed for social anxiety symptoms using standardized self-report instruments and a Trier Social Stress Test (TSST) modified for continuous psychophysiological monitoring. Ambulatory monitoring of home sleep will also be obtained using actigraphy and sleep diaries. The investigators hypothesize that, post treatment, those individuals who napped will show greater questionnaire-based clinical improvement as well as lesser psychophysiological reactivity during the modified TSST compared to those who remained quietly awake. The investigators further hypothesize that characteristics of sleep quality and architecture during naps, specifically durations of total sleep, REM and slow-wave sleep, as well as REM continuity, will predict greater clinical improvement and lesser psychophysiological reactivity to the TSST in those who napped following their third and fourth therapy sessions. Positive results will provide the first proof-of-principle for sleep augmentation of exposure therapy for clinically significant extreme social anxiety.

Detailed description: Widely replicated studies demonstrate that sleep can enhance memory consolidation. Potential clinical applications of such findings have only begun to be explored. The investigators have recently shown that nocturnal sleep following simulated exposure therapy for high levels of spider fear reduced both psychophysiological and self-reported reactivity when participants were re-exposed to the same and to novel spider stimuli. The proposed research will extend these findings to the more debilitating and clinically important condition of extreme social anxiety. The investigators will examine whether post-exposure naps can be used to strengthen therapeutic extinction memories formed during exposure exercises used in the behavioral treatment of extreme social anxiety. A total of 32 individuals with high levels of social anxiety, evidenced by scores of 60 or greater on the Liebowitz Social Anxiety Scale, self-report during a clinical interview and demonstrated enhanced psychophysiological reactivity when imagining a socially stressful scenario, will be enrolled in an exposure-based group treatment for extreme social anxiety. Eight successive therapy groups of 4 patients each will be offered during the 2-year funding period. The third and fourth sessions of this validated 5-week/5-session treatment will involve each participant delivering a speech on a topic individually chosen to elicit significant social anxiety. Following both of these sessions, all 4 participants will go to the nearby Massachusetts General Hospital sleep laboratory where 2 will be given a 2-hour sleep opportunity with polysomnographic (PSG) monitoring and the other 2 will be similarly instrumented but undergo 2 hours of monitored quiet wakefulness (prior to session 3 participants will be randomized to the sleep or wakefulness arm). Before beginning treatment and within several days following the final treatment session, all participants will be individually assessed for social anxiety symptoms using standardized self-report instruments. At these same times, they will undergo a Trier Social Stress Test (TSST) modified for continuous psychophysiological monitoring that also includes repeated Subjective Units of Distress (SUDS) self report and sampling for salivary cortisol. In addition to laboratory PSG, ambulatory monitoring of home sleep with actigraphy and sleep diaries will take place at pre-treatment baseline and during the last 3 weeks of treatment. The investigators hypothesize that those individuals allowed a 2-hour sleep opportunity following exposure sessions, compared to those who remained quietly awake, will show greater questionnaire-based clinical improvement as well as lesser psychophysiological and SUDS reactivity during the modified TSST. The investigators further hypothesize that characteristics of sleep quality and architecture during naps, specifically durations of total sleep, REM sleep and slow-wave sleep as well as REM continuity, will predict clinical improvement and diminished TSST reactivity in those who napped. To help ensure that observed sleep effects are attributable to the two 2-hour sleep opportunities, the investigators will control for actigraph and diary-measured sleep quality during treatment. Positive results will provide the first proof-of-principle for sleep augmentation of exposure therapy for a clinically significant extreme social anxiety.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria:

1. Treatment-seeking individuals diagnosed with Social Anxiety Disorder using the Structured Clinical Interview for DSM-IV56 (DSM-5 SCID once available)
2. A score \> 60 on the Liebowitz Social Anxiety Scale (LSAS)13
3. 18-40 years of age
4. Proficient in English
5. Normal or corrected to normal vision
6. Able to give informed consent
7. Willingness and ability to comply with the requirements of the study protocol
8. Meets psychophysiological screening criteria for inclusion carried out as follows:

   * During a 5-min. baseline period, the candidate participant will sit quietly with skin conductance and orbicularis oculi EMG levels being recorded.
   * Toward the end of this period a loud acoustic stimulus will be presented several times and blink startle EMG and SCR will be recorded.
   * The candidate subject will then be asked to describe, for 2 min., their most fearful and upsetting past social experience.
   * They will then be instructed to silently reimagine this experience as vividly as possible.
   * During this imagination period, the loud acoustic stimulus will again be presented several times and blink startle EMG and SCR will be recorded.
   * Participants for whom mean SCR and blink startle EMG during the imagining period measurably exceed the means of these measures during baseline will be retained in the study whereas those for whom these measures do not change or are reduced will be excluded.
   * This procedure will help ensure that those included in the study will show potentiation of physiological reactivity while anticipating exposure to public speaking.

Exclusion Criteria:

1. Any potentially confounding medical illness
2. Lifetime history of any neurological illness or injury including neurodegenerative disorders or dementia, stroke, seizure disorders, neurosurgical procedures, head injury resulting in loss of consciousness for greater than 5 min.
3. Lifetime history, diagnosed by DSM-IV criteria (or DSM-5 once its SCID available), of bipolar disorder, schizophrenia or other psychotic disorder, pervasive developmental disorder, chronic mental disorder due to a medical condition or other potentially confounding chronic mental disorder.
4. Current major depressive, dysthymic or anxiety disorder other than Social Anxiety Disorder or other potentially confounding current mental disorder diagnosed by DSM-IV criteria (or DSM-5 once its SCID available).
5. DSM-IV substance abuse or dependence within the last year, lifetime history of hospitalization for substance abuse (determined at clinical interview) or positive urine toxicology screen at the time of the clinical interview
6. Any evidence of suicidal ideation, violent behavior or psychosis at the clinical interview
7. Use of psychiatric medication within 4 weeks of study (with the exception of 6 weeks for fluoxetine)
8. Current psychotherapy for Social Anxiety Disorder
9. Any indication of a sleep disorder, particularly sleep-disordered breathing, on the Pittsburgh Structured Clinical Interview for Sleep Disorders
10. Sleep onset latency \> 1 hr, total sleep time \< 5 hr or typical bed time later than 3 AM
11. Overnight shift work or recent travel across multiple time zones
12. \> 4 caffeinated beverages per day or \> 11 alcoholic beverages per week
13. Nicotine use

Primary outcomes:
measure: Leibowitz Social Anxiety Scale
timeFrame: 5 weeks
measure: Fear-potentiated startle
timeFrame: 5 weeks
Secondary outcomes:
measure: Fear of Negative Evaluation Scale
timeFrame: 5 weeks
measure: Social Phobia and Anxiety Inventory
timeFrame: 5 weeks
measure: Clinical Global Impressions Scale
timeFrame: 5 weeks
measure: Pre- to-post TSST change in Spielberger State-Trait Anxiety Inventory-State portion score
timeFrame: up to 5 weeks
measure: Subjective Units of Distress Ratings
timeFrame: 5 weeks
measure: Pre- to-post TSST change in salivary cortisol
timeFrame: up to 5 weeks
measure: Fear potentiation of loud-tone evoked heart-rate acceleration (HRA) and skin conductance response (SCR)
timeFrame: 5 weeks
measure: Increase in baseline heart rate from baseline to performance phases of TSST
timeFrame: up to 5 weeks
measure: Increase in mean corrugator supercilii EMG from baseline to performance phases of TSST
timeFrame: 5 weeks
Other outcomes:
measure: NEO-PI-R Neuroticism and Extraversion total scores
timeFrame: 5 weeks
measure: Social Avoidance and Distress Scale
timeFrame: 5 weeks
measure: Social Probability and Social Cost Questionnaire
timeFrame: 5 weeks
measure: Pre- to-post TSST change in Positive and Negative Affect Scale subtotals
timeFrame: up to 5 weeks
measure: Pre- to-post TSST change in Stanford Sleepiness Scale subtotals
timeFrame: up to 5 weeks
measure: Rate and number of spontaneous SCRs during baseline, preparation and performance phases of TSST
timeFrame: 5 weeks
measure: Rate of mean HR decline from performance to late recovery phases of the TSST
timeFrame: 5 weeks
measure: Social Interaction Self-Statements Test
timeFrame: 5 weeks
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital, One Bowdoin Square
state: Massachusetts
city: Charlestown
country: United States
facility: Massachusetts General Hospital-East, Building 149
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital and Harvard Medical School
name: Edward F Pace-Schott, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pace-Schott EF, Verga PW, Bennett TS, Spencer RM. Sleep promotes consolidation and generalization of extinction learning in simulated exposure therapy for spider fear. J Psychiatr Res. 2012 Aug;46(8):1036-44. doi: 10.1016/j.jpsychires.2012.04.015. Epub 2012 May 10.
citation: Zalta AK, Dowd S, Rosenfield D, Smits JA, Otto MW, Simon NM, Meuret AE, Marques L, Hofmann SG, Pollack MH. Sleep quality predicts treatment outcome in CBT for social anxiety disorder. Depress Anxiety. 2013 Nov;30(11):1114-20. doi: 10.1002/da.22170. Epub 2013 Aug 26.
citation: Pace-Schott EF, Bottary RM, Kim SY, Rosencrans PL, Vijayakumar S, Orr SP, Lasko NB, Goetter EM, Baker AW, Bianchi MT, Gannon K, Hoeppner SS, Hofmann SG, Simon NM. Effects of post-exposure naps on exposure therapy for social anxiety. Psychiatry Res. 2018 Dec;270:523-530. doi: 10.1016/j.psychres.2018.10.015. Epub 2018 Oct 9.