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

NCT ID: NCT03068429

Last Updated: 2021-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-01
• Study Completion Date: 2020-07-31

Brief Summary

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.

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

Conditions

Obsessive-Compulsive Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Sertraline open label

Sertraline hydrochloride up to 200mg/day or maximum tolerated dosage for 4-weeks.

Group Type: EXPERIMENTAL

Sertraline Hydrochloride

Intervention Type: DRUG

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

Interventions

Sertraline Hydrochloride

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

Intervention Type: DRUG

Other Intervention Names

sertraline 50mg; zoloft

Eligibility Criteria

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)
• being pregnant or at risk of becoming pregnant

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Juliana Belo Diniz

Psychiatrist, principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juliana B Diniz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Researcher

Locations

Institute of Psychiatry, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo

São Paulo, , Brazil

Countries

Brazil

Other Identifiers

0182/11

Identifier Type: -

Identifier Source: org_study_id