Generalization of Extinction Learning

Sponsor

University of California, Los Angeles (Other)

Overall Status

Completed

CT.gov ID

NCT01900301

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Social Anxiety Disorder	Drug: Scopolamine Drug: intranasal placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Cholinergic Decontextualization of Exposure Therapy for Anxiety

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Scopolamine .4mg 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 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
Placebo Comparator: Intranasal placebo Participants will be randomized to a placebo, administered via nasal drops, prior to each session of exposure therapy	Drug: intranasal placebo Participants will be randomized to a drug placebo, administered via nasal drops, prior to each session of exposure therapy
Experimental: Scopolamine .5mg 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 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
Experimental: Scopolamine .6mg 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 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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

participant report of a diagnosed medical or neurological disorder
prescription or over the counter medications that can interact with Scopolamine, such as anticholinergic medications (e.g. belladonna alkaloids, antihistamines, meclizine, tricyclic antidepressants, and muscle relaxants), cold medicines, cough suppressants. Other drugs that will be reasons for exclusion include: antimuscarinics, nifedipine, parasympathomimetics, amantadine, amoxapine, antacids, antidiarrheals, anxiolytics, hypnotics, atomexetine, bupropion, cisapride, clozapine, cyclobenzaprine, digoxin, disopyramide, dronabinol (THC), ethanol, maprotilline, memantine, metoclopramide, nabilone, olanzapine, opiate agonists, orphenadrine, phenothiazines, potassium salts, quinidine, sedating H1-blockers, topiramate, tricyclic antidepressants, erthyromycin, ketoconazole, and tegaserod.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095

Sponsors and Collaborators

University of California, Los Angeles

Investigators

Principal Investigator: Michelle G. Craske, Ph.D., Department of Psychology, UCLA
Principal Investigator: Michael Fanselow, Ph.D., Department of Psychology, UCLA