Generalization of Extinction Learning

NCT01900301 | Completed Phase 1 DMC

• 1 other identifier: MH101359-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Fear, whether it occurs in humans suffering from an anxiety disorder or in experimental models with rodents, is reduced by exposing the frightened organism to the fearful stimulus in the absence of any negative consequences (i.e., extinction, or exposure therapy). However, fear often renews when the feared stimulus is encountered in a context different from the exposure context. In rats, the investigators found that interfering with the animal's ability to process contexts during extinction by administering an anticholinergic drug prevented fear renewal. This proposal will determine if the beneficial effect of this drug translates to exposure therapy in socially anxious humans. To this end, 100 individuals with Social Phobia who fear public speaking will undergo repeated sessions of exposure to public speaking, within a virtual reality context. Participants will be randomized to either drug placebo, .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy. One month after completion of exposure therapy, context renewal will be tested by comparing physiological and subjective responses to public speaking in the same virtual context as used during exposure therapy versus a context different than the one used during exposure therapy. The goal is to identify the dose of Scopolamine associated with the greatest reduction in context renewal. In addition, a secondary analysis will attempt to identify those individuals who benefit most from Scopolamine-augmentation of exposure therapy.

Conditions

Social Anxiety Disorder

Keywords

exposure; scopolamine; extinction learning; social anxiety

Outcome Measures

Primary Outcomes (3)

• Eye blink startle reflex

  change from final exposure session to follow-up (8 weeks following baseline)

• Skin conductance responses and heart rate

  change from final exposure session to follow-up (8 weeks following baseline)

• Subjective Units of Distress

  change from final exposure session to follow-up (8 weeks following baseline)

Secondary Outcomes (3)

• Self Statements During Public Speaking Scale

  change from baseline to follow-up (8 weeks following baseline)

• Personal Report of Confidence as a Speaker Scale

  change from baseline to follow-up (8 weeks following baseline)

• Subjective units of distress during in vivo speech

  change from baseline to follow-up (8 weeks following baseline)

Study Arms (4)

Scopolamine .4mg

EXPERIMENTAL

Participants will be randomized to either .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy

Drug: Scopolamine

Intranasal placebo

PLACEBO COMPARATOR

Participants will be randomized to a placebo, administered via nasal drops, prior to each session of exposure therapy

Drug: intranasal placebo

Scopolamine .5mg

EXPERIMENTAL

Participants will be randomized to either .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy

Drug: Scopolamine

Scopolamine .6mg

EXPERIMENTAL

Participants will be randomized to either .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy

Drug: Scopolamine

Interventions

Scopolamine DRUG

Participants will be randomized to either, .4mg/.01 mL Scopolamine, .5mg/.01 mL Scopolamine or .6mg/.01 mL Scopolamine, administered via nasal drops, prior to each session of exposure therapy

Scopolamine .4mg; Scopolamine .5mg; Scopolamine .6mg

intranasal placebo DRUG

Participants will be randomized to a drug placebo, administered via nasal drops, prior to each session of exposure therapy

Intranasal placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• between the ages of 18 and 55,
• fluent in English,
• within normal body weight (BMI=18.5 to 24.9)
• meet DSM-IV diagnostic criteria for Social Phobia and report a fear of public speaking.

You may not qualify if:

• participant report of a diagnosed medical or neurological disorder
• over the counter drugs or substances that may have a sedative effect (e.g. herbal sedatives: ashwagandha, Duboisia hopwoodii, Prostanthera striatiflora, kava, mandrake, valerian, cannabis, passiflora incarnate; Antihistamines: Diphenhydramine, Dimenhydrinate, Doxylamine, Promethazine; Alcohol; Dextromethorphan)
• individuals with urinary problems (e.g., BPH)
• pregnant or nursing females (as the effect of Scop on fetuses is not known)
• suicidality
• delusions or hallucinations
• history of substance dependence in last five years or substance abuse within the past 6 months

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Craske MG, Fanselow M, Treanor M, Bystritksy A. Cholinergic Modulation of Exposure Disrupts Hippocampal Processes and Augments Extinction: Proof-of-Concept Study With Social Anxiety Disorder. Biol Psychiatry. 2019 Nov 1;86(9):703-711. doi: 10.1016/j.biopsych.2019.04.012. Epub 2019 Apr 19.

  PMID: 31174846 DERIVED

MeSH Terms

Conditions

Phobia, Social

Interventions

Scopolamine

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Michelle G. Craske, Ph.D.

  Department of Psychology, UCLA

  PRINCIPAL INVESTIGATOR

• Michael Fanselow, Ph.D.

  Department of Psychology, UCLA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Psychology

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 16, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: October 7, 2019

Record last verified: 2019-10

Locations

US (1)