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

• ClinicalTrials.gov Identifier: NCT01733030
• Recruitment Status: Completed
• First Posted: November 26, 2012
• Last Update Posted: May 4, 2017
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

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 or disease	Intervention/treatment
Post Traumatic Stress Syndrome	Drug: Seromycin

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 56 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: The Effects of D-cycloserine on Stimulus Generalization of Conditioned Fear in Healthy Controls.
• Study Start Date: January 2013
• Actual Primary Completion Date: October 1, 2015
• Actual Study Completion Date: October 1, 2015

Groups and Cohorts

Group/Cohort	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. fMRI (BOLD) responses [ Time Frame: 1/1/13-6/1/14 ]
   fMRI (BOLD) responses

Secondary Outcome Measures :

1. Behavioral assessments of perceived danger [ Time Frame: up to three years ]
   Behavioral assessments of perceived danger

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Minnesota

University of MInnesota

Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Shmuel Lissek, PhD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01733030
• Other Study ID Numbers: MH080130
• First Posted: November 26, 2012
• Last Update Posted: May 4, 2017
• Last Verified: May 2017

Keywords provided by University of Minnesota:

PTSD

Additional relevant MeSH terms:

Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Cycloserine; Anti-Infective Agents, Urinary; Anti-Infective Agents; Renal Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action