The Effects of D-cycloserine on Stimulus Generalization of Conditioned Fear Healthy Controls. (DCS)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01733030
First received: November 19, 2012
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

PROJECT SUMMARY:

PTSD is a debilitating psychiatric condition precipitated by exposure to extreme, or life threatening, trauma with an estimated lifetime prevalence between 8% and 9% in U.S. adults. One core symptom of PTSD is intense psychological distress in the presence of stimuli that "resemble" one or more aspects of the trauma experience (DSM-IV). This phenomenon referred to as stimulus generalization has received surprisingly little empirical testing in the context of clinical anxiety in general, and PTSD more specifically. The current proposal represents the first effort to study the neurobiology and pharmacology of this PTSD-relevant learning phenomenon across those with and without PTSD. The objective of this particular proposal is to apply fMRI and pharmacologic methods to: 1) identify brain mechanisms associated with generalization of conditioned fear and 2) examine the pharmacologic modifiability of levels of generalization using a partial agonist at the NMDA receptor complex (D-cycloserine) shown to increase discrimination of CS+ (danger cue) and CS- (safety cue) in animal studies.


Condition Intervention
3 Conditions Including 250 mg Syromycin, 500 mg Seromycin, and Placebo.
Drug: Seromycin

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: The Effects of D-cycloserine on Stimulus Generalization of Conditioned Fear in Healthy Controls.

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • fMRI (BOLD) responses [ Time Frame: 1/1/13-6/1/14 ] [ Designated as safety issue: No ]
    fMRI (BOLD) responses


Secondary Outcome Measures:
  • Behavioral assessments of perceived danger [ Time Frame: up to three years ] [ Designated as safety issue: No ]
    Behavioral assessments of perceived danger


Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
250 mg Seromycin
Healthy adults who will receeve one administration of 250 mg of Seromycin prior to the start of the study.
Drug: Seromycin
250 mg versus 500 mg versus placebo effects on conditioned fear generalization
Other Name: D-cycloserine
Drug: Seromycin
500 mg Seromycin
Healthy adults who will recieve one administration of 500 mg of Seromycin prior to the start of the study.
Drug: Seromycin
250 mg versus 500 mg versus placebo effects on conditioned fear generalization
Other Name: D-cycloserine
Drug: Seromycin
Placebo
Healthy adults who will receive one administration of a placebo pill prior to the start of the study.

Detailed Description:

To fullfill the objectives of this application, a generalization paradigm has been designed and psychophysiologically validated in which 6 rings presented on a computer screen gradually increase in size. For half of participants the smallest ring is the conditioned stimulus paired with electric shock (CS+) and the largest is the unpaired stimulus (CS-), and for the other half of participants this is reversed. Activity in fear-related brain structures measured via fMRI are predicted to gradually decrease as the presented stimulus gradually becomes less similar to the CS+, forming a generalization slope or gradient. One central hypothesis of the current application is that DCS (Seromycin) will dose dependently increase the steepness of generalization gradients (i.e., reduce fear generalization). This study will include 3 groups of healthy adults recieving either 1) 500 mg Seromycin, 2) 250 mg Seromycin, or placebo only prior to acquisition of fear conditioning. Twenty four hours later, participants will return to complete an fMRI during which brain responses to the danger cue and stimuli resembling the danger cue will be assessed.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Healthy adults between the ages of 18-55.

Criteria

Inclusion Criteria:

  • Healthy adults between the ages of 18-55.

Exclusion Criteria:

  1. Current or past Axis I psychiatric diagnosis as determined by self report
  2. Current substance dependence or meet criteria for the six month period preceding testing.
  3. Participants will be excluded if they have current or past medical illnesses, which place the participant at risk or confound the results of the study including:

    A) Past history of hypersensitivity to Seromycin B) Current or past epileptic disorders C) Current depression D) Current anxiety disorders E) Current or past psychotic disorders F) Current or past renal disease G) Excessive or concurrent use of alcohol

    a) Subjects who are unable to abstain from alcohol for 12 hours prior to testing and 2 days following testing will be excluded

  4. Current use of psychoactive medications or medications that alter central-nervous-system function
  5. Females who are pregnant or currently breast-feeding
  6. Any metallic implants or objects above the knee, tattoos about the knee, or oral braces.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01733030

Locations
United States, Minnesota
University of MInnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Shmuel Lissek, PhD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01733030     History of Changes
Other Study ID Numbers: MH080130
Study First Received: November 19, 2012
Last Updated: March 18, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014