Generalization of Extinction Learning

NCT ID: NCT01900301

Last Updated: 2019-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2017-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Scopolamine

Intervention Type: 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

Intranasal placebo

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

Group Type: PLACEBO_COMPARATOR

intranasal placebo

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Scopolamine

Intervention Type: 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 .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

Group Type: EXPERIMENTAL

Scopolamine

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

intranasal placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Michelle Craske

Professor, Department of Psychology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michelle G. Craske, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Psychology, UCLA

Michael Fanselow, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Psychology, UCLA

Locations

University of California, Los Angeles

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31174846 (View on PubMed)

Other Identifiers

MH101359-01

Identifier Type: -

Identifier Source: org_study_id