Clinical trial NCT01900301: Generalization of Extinction Learning
Official title: Cholinergic Decontextualization of Exposure Therapy for Anxiety
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Social Anxiety Disorder
Keywords: exposure
scopolamine
extinction learning
social anxiety
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2013-07-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Eye blink startle reflex
timeFrame: change from final exposure session to follow-up (8 weeks following baseline)
measure: Skin conductance responses and heart rate
timeFrame: change from final exposure session to follow-up (8 weeks following baseline)
measure: Subjective Units of Distress
timeFrame: change from final exposure session to follow-up (8 weeks following baseline)
Secondary outcomes:
measure: Self Statements During Public Speaking Scale
timeFrame: change from baseline to follow-up (8 weeks following baseline)
measure: Personal Report of Confidence as a Speaker Scale
timeFrame: change from baseline to follow-up (8 weeks following baseline)
measure: Subjective units of distress during in vivo speech
timeFrame: change from baseline to follow-up (8 weeks following baseline)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
affiliation: Department of Psychology, UCLA
name: Michelle G. Craske, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychology, UCLA
name: Michael Fanselow, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.