Fear Conditioned Response in Healthy Subjects and in OCD Patients Pre and Post Treatment With Sertraline. (FEARCON)

April 26, 2021 updated by: Juliana Belo Diniz, University of Sao Paulo

Fear Conditioning, Extinction and Recall in Healthy Subjects and in Obsessive-compulsive Disorder Patients Pre and Post Treatment With Sertraline.

24 OCD patients and 24 healthy subjects will be submitted to a two-day fear conditioning paradigm during acquisition of functional magnetic resonance imaging (fMRI). OCD patients will be submitted to the paradigm at two timepoints: baseline and 4 weeks after treatment initiation with sertraline up to 200mg/day or maximum tolerated dosage. OCD patients are expected to demonstrate worsened extinction retention compared to healthy subjects at baseline. Sertraline treatment is expected to improve extinction retention compared to baseline and to normalize the brain regions being recruited with the conditioned stimuli presented during the recall phase.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Fear conditioning paradigms are used to investigate the learning process of the fear response in patients with psychiatric disorders and healthy subjects. Patients with post traumatic stress disorder have been shown to fail to retrieve the memory of fear extinction during the recall phase of the fear conditioning paradigm when compared to healthy subjects. In one previous trial, obsessive-compulsive disorder (OCD) patients have demonstrated the same failure to recall extinction and the results from functional magnetic resonance imaging (fMRI) activation maps have shown different regions being recruited during recall when compared with healthy subjects. However, in that previous trial, some of the OCD patients included were already taking medication for OCD. In the current trial, we will evaluate 24 unmedicated OCD patients with a two-day fear conditioning paradigm before and after 4-weeks of treatment initiation with sertraline up to 200mg/day or maximum tolerated dosage. Sertraline is a first-line treatment option for OCD. At baseline, OCD patients will be compared to 24 healthy subjects. At post treatment, fear conditioning and fMRI results wil be compared to baseline. OCD patients are expected to demonstrate worsened extinction retention compared to healthy subjects at baseline. Sertraline treatment is expected to improve extinction retention compared to baseline and to normalize the brain regions being recruited with the conditioned stimuli presented during the recall phase. By "normalize" we mean that after treatment the regions being recruited will be the same as the ones recruited by healthy subjects during baseline, in other words, differences found at baseline regarding brain activation by the conditioned stimuli are expected to disappear after treatment.

Abbreviations: CS= conditioned stimuli, CS+= conditioned stimuli to shock, CS-=neutral conditioned stimuli, CS+E= extinguished conditioned stimuli to shock, CS+U=unextinguished conditioned stimuli to shock

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sao Paulo, Brazil, 05403-010
        • Institute of Psychiatry, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Healthy controls

-willingness to participate in research

OCD patients

  • willingness to participate in research
  • main diagnosis of OCD (psychiatric clinical evaluation)
  • minimum YBOCS (Yale Brown Obsessive-compulsive severity scale) score of 16 points

Exclusion Criteria:

Healthy controls

  • any current psychiatric diagnosis according to evaluation using semi structured interview for DSM IV diagnoses (SCID I)
  • any past psychiatric diagnoses except single major depression episode and simple phobia (evaluation by semi structure interview-SCID I)
  • current use of psychotropic medications (last use has to be at least 3 months prior to study initiation)
  • chronic use of any medications except vitamins and contraceptives
  • MRI exclusionary criteria (metal implants, recently made tatoos, claustrophobia, etc)
  • being pregnant

OCD patients

  • comorbidity with neurodevelopmental disorders (autism, mental retardation), current psychotic disorders, current substance dependence or abuse, bipolar mood disorder according to evaluation using semi structured interview for DSM IV diagnoses (SCID I)
  • current use of psychotropic medications (last use has to be at least 3 months prior to study initiation)
  • MRI exclusion criteria(metal implants, recently made tatoos, claustrophobia, etc)
  • being pregnant or at risk of becoming pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sertraline open label
Sertraline hydrochloride up to 200mg/day or maximum tolerated dosage for 4-weeks.
first week: sertraline hydrochloride 50mg/day, second week: sertraline hydrochloride 100mg/day, third week: sertraline hydrochloride 150mg/day, fourth week: sertraline hydrochloride 200mg/day OBS.: Other SSRIs (fluoxetine, paroxetine, escitalopram) with equivalent dosage schedules can be used if patients report prior intolerance to sertraline
Other Names:
  • zoloft
  • sertraline 50mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Main behavioral measure (extinction retention index)
Time Frame: Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group
Equation: 100-((MEAN(2 first CS+E during recall)/MAXIMUM(2 last CS+E during extinction))*100)
Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group
Main functional neuroimaging measure
Time Frame: Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group
ventro medial prefrontal cortex (vmPFC) activation during recall phase
Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group
Main treatment outcome measure
Time Frame: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Yale Brown Obsessive Compulsive Scale reduction (final score minus initial score)
Change from baseline to 4 weeks after treatment initiation (only interventional group)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Main behavioral measure baseline comparison (extinction retention index OCD patients versus healthy subjects)
Time Frame: Baseline
Equation: 100-((MEAN(2 first CS+E during recall)/MAXIMUM(2 last CS+E during extinction))*100)
Baseline
Main functional neuroimaging measure (activation maps for contrast CS+E versus CS-during recall phase,OCD patients versus healthy subjects)
Time Frame: Baseline (all subjects)
ventro medial prefrontal cortex (vmPFC) activation during recall phase
Baseline (all subjects)
Secondary behavioral measure (learning- conditioning index, OCD patients pre and post treatment)
Time Frame: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Equation: MEAN(all CS+ during conditioning)-MEAN(all CS- during conditioning)
Change from baseline to 4 weeks after treatment initiation (only interventional group)
Secondary behavioral measure (learning- conditioning index, OCD patients versus healthy subjects)
Time Frame: Baseline (all subjects)
Equation: MEAN(all CS+ during conditioning)-MEAN(all CS- during conditioning)
Baseline (all subjects)
Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients pre and post treatment)
Time Frame: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Equation: MEAN(first two CS+U during renewal)-MEAN(first two CS+U during recall)
Change from baseline to 4 weeks after treatment initiation (only interventional group)
Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients versus healthy subjects)
Time Frame: Baseline (all subjects)
Equation: MEAN(first two CS+U during renewal)-MEAN(first two CS+U during recall)
Baseline (all subjects)
Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients pre and post treatment)
Time Frame: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Gain in amygdala activation during conditioning for CS+ presentations
Change from baseline to 4 weeks after treatment initiation (only interventional group)
Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients versus healthy subjects)
Time Frame: Baseline (all subjects)
Gain in amygdala activation during conditioning for CS+ presentations
Baseline (all subjects)
Secondary functional neuroimaging measure (functional activation maps for contrast CS+E/CS- during recall phase of baseline measurement, OCD patients versus healthy subjects)
Time Frame: Baseline (all subjects)
Alternative activations (OCD patients versus controls), regions other than the vmPFC, activated with CS+ presentations during recall
Baseline (all subjects)
Secondary functional neuroimaging measure (functional activation maps for contrast CS+E/CS- during recall phase comparing change between post and pre treatment)
Time Frame: Change between baseline and 4 weeks after treatment initiation (only interventional group)
Alternative activations (OCD patients post treatment compared with baseline), regions other than the vmPFC, activated with CS+E presentations during recall
Change between baseline and 4 weeks after treatment initiation (only interventional group)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Juliana B Diniz, MD, PhD, Researcher

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Actual)

December 20, 2019

Study Completion (Actual)

July 31, 2020

Study Registration Dates

First Submitted

February 22, 2017

First Submitted That Met QC Criteria

February 24, 2017

First Posted (Actual)

March 1, 2017

Study Record Updates

Last Update Posted (Actual)

April 27, 2021

Last Update Submitted That Met QC Criteria

April 26, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The spreadsheet with main results will be made available along main publication

IPD Sharing Time Frame

Data is estimated to be available at study completion. Completion date is estimated to be july/2020.

IPD Sharing Access Criteria

There will be no restrictions to acess of unindentified data results.

IPD Sharing Supporting Information Type

  • Statistical Analysis Plan (SAP)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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