Generalization of Extinction Learning

Study Overview
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Brief Summary
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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.

Official Title
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Cholinergic Decontextualization of Exposure Therapy for Anxiety

Conditions
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Social Anxiety Disorder

Intervention / Treatment
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* Drug: Scopolamine
* Drug: intranasal placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exposure, scopolamine, extinction learning, social anxiety