Pilot Study of Pharmaceutical and Behavioral Interventions to Treat Anxiety Disorders

NCT01631682 | Completed Phase 4 Results DMC

• 1 other identifier: W81XWH-11-2-0092
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this project is to create fear conditioning paradigm within which the relative strengths of various novel pharmacological and behavioral interventions can be tested. These interventions are intended to reduce the fearfulness associated with fear conditioning by blocking a memory process known as reconsolidation. In fear conditioning, a "conditioned" stimulus (CS) is paired with an aversive "unconditioned" stimulus (US) such as an electric shock, until presentation of the CS alone comes to elicit a fear conditioned response (CR). The investigators hypothesize that by using a more highly prepared CS (i.e. video of spiders); more sensitive subjects (individuals with stronger acquired CRs); and additional experimental probes for the presence of the latent CR, the investigators may develop a normal human paradigm that is not plagued by previously observed floor effects (i.e. intervention is 100% effective), within which both the established techniques of propranolol and delayed extinction will produce significant, but only partial, CR reduction. This would leave room to test and compare potentially more powerful candidate reconsolidation-blocking or memory-updating interventions. To achieve these aims, subjects will undergo a four-day fear conditioning and delayed extinction protocol. Skin conductance response data will be gathered across the different phases of the experiment.

Conditions

Posttraumatic Stress Disorder; Anxiety Disorder

Keywords

Posttraumatic Stress Disorder; PTSD; Anxiety; Fear of spiders; Reconsolidation; Reconsolidation blockade

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Skin Conductance Response

  Skin conductance response (SCR) is the change in skin conductance level in response to a stimulus. We compared the SCR to a non-treated conditioned stimulus (CS+N) with the SCR to a treated conditioned stimulus (CS+R) by creating a difference score (CS+R - CS+N) for the day 3 data. Day 3 is 48 hours after the fear-conditioning procedure and serves as the primary measure of whether the treatment had an effect. SCR was measured in microSiemens; the SCR difference score reflects a change in microSiemens.

  48hrs

Study Arms (4)

Propranolol

ACTIVE COMPARATOR

a single dose of 40mg propranolol may be given to begin visit 2, followed by 90min wait and subsequently CS reactivation

Drug: Propranolol

Reactivation with time delay

ACTIVE COMPARATOR

For those not receiving propranolol on visit 2, one experimental CS will be reactivated, followed by a 10 minute break and subsequently extinction

Behavioral: Reactivation

Mifepristone

EXPERIMENTAL

a single dose of 1800mg (200mg tablets) mifepristone may be given to begin visit 2, followed by 90min wait and subsequently CS reactivation

Drug: Mifepristone

Intranasal oxytocin

EXPERIMENTAL

A single 32IU dose of Syntocinon (intranasal oxytocin) is given to begin visit 2, followed by a 10 minute wait and subsequent CS reactivation.

Drug: Intranasal oxytocin

Interventions

Propranolol DRUG

40mg single pill

Also known as: Inderal

Propranolol

Reactivation BEHAVIORAL

subject is re-exposed to CS+R on day 2 (code for CS that is both paired with shock and reactivated on day 2)

Reactivation with time delay

Mifepristone DRUG

1800mg, 9 tablets

Also known as: Mifeprex, Korlym

Mifepristone

Intranasal oxytocin DRUG

32 IU, 8 self-administered intranasal sprays, 4 in each nostril

Also known as: Syntocinon

Intranasal oxytocin

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-35
• Top half of the normal human distribution of the Spider Phobia Questionnaire-15

You may not qualify if:

• Any criteria for diagnosable spider phobia
• Any current Axis I mental disorder on the Structured Clinical Interview for DSM-IV (SCID)
• Presence of drugs of abuse (e.g. opiates, marijuana, cocaine, or amphetamines) per urine screen
• Non-English speaking (due to lack of validated questionnaires/instruments in other languages)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (2)

• Fricchione J, Greenberg MS, Spring J, Wood N, Mueller-Pfeiffer C, Milad MR, Pitman RK, Orr SP. Delayed extinction fails to reduce skin conductance reactivity to fear-conditioned stimuli. Psychophysiology. 2016 Sep;53(9):1343-51. doi: 10.1111/psyp.12687. Epub 2016 Jun 17.

  PMID: 27314560 RESULT

• Spring JD, Wood NE, Mueller-Pfeiffer C, Milad MR, Pitman RK, Orr SP. Prereactivation propranolol fails to reduce skin conductance reactivity to prepared fear-conditioned stimuli. Psychophysiology. 2015 Mar;52(3):407-15. doi: 10.1111/psyp.12326. Epub 2014 Sep 16.

  PMID: 25224026 RESULT

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Anxiety Disorders; Arachnophobia

Interventions

Propranolol; Mifepristone; Oxytocin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Scott P. Orr, Ph.D.
• Organization: Massachusetts General Hospital

scott_orr@hms.harvard.edu

617-643-7269

Study Officials

• Scott P. Orr, Ph.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychology

Study Record Dates

• First Submitted: June 25, 2012
• First Posted: June 29, 2012
• Study Start: November 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: February 23, 2017
• Results First Posted: February 23, 2017

Record last verified: 2017-01

Locations

US (1)