Generalization of Extinction Learning

University of California, Los Angeles (UCLA)

Status and phase: Completed; Phase 1

Conditions: Social Anxiety Disorder

Treatments: Drug: intranasal placebo; Drug: Scopolamine

Study type: Interventional

Funder types: Other

Identifiers

NCT01900301

MH101359-01

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. participant report of a diagnosed medical or neurological disorder
2. 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.
3. 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)
4. individuals with urinary problems (e.g., BPH)
5. pregnant or nursing females (as the effect of Scop on fetuses is not known)
6. suicidality
7. delusions or hallucinations
8. history of substance dependence in last five years or substance abuse within the past 6 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 4 patient groups, including a placebo group

Scopolamine .4mg

Experimental group

Description:

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

Treatment:

Drug: Scopolamine

Intranasal placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: intranasal placebo

Scopolamine .5mg

Experimental group

Description:

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

Treatment:

Drug: Scopolamine

Scopolamine .6mg

Experimental group

Description:

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

Treatment:

Drug: Scopolamine