Obsessive-Compulsive DisorderPhase 4FEARCONNCT03068429
Fear Conditioned Response in Healthy Subjects and in OCD Patients Pre and Post Treatment With Sertraline.
A Phase 4 study testing Sertraline Hydrochloride in people with Obsessive-Compulsive Disorder, run by University of Sao Paulo at 1 site in Brazil.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obsessive-Compulsive Disorder
- What is being tested?
- Sertraline Hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Dec 2016to 31 Jul 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Institute of Psychiatry, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo
São Paulo, 05403-010
About this study
Official title: 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.
Read the 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
- Being tested
- Sertraline Hydrochloride
- Keywords
- obsessive-compulsive disorder, fear conditioning, functional neuroimaging, sertraline
- Medical subject headings
- Obsessive-Compulsive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sertraline HydrochlorideDrug
Also called sertraline 50mg, zoloft
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
| Study group | Role | What they receive |
|---|---|---|
| Sertraline open label | Experimental | Sertraline hydrochloride up to 200mg/day or maximum tolerated dosage for 4-weeks. Receives: Drug: Sertraline Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main behavioral measure (extinction retention index)
Equation: 100-((MEAN(2 first CS+E during recall)/MAXIMUM(2 last CS+E during extinction))*100)
Measured: 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
ventro medial prefrontal cortex (vmPFC) activation during recall phase
Measured: 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
Yale Brown Obsessive Compulsive Scale reduction (final score minus initial score)
Measured: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Secondary outcomes (10)
Main behavioral measure baseline comparison (extinction retention index OCD patients versus healthy subjects)
Equation: 100-((MEAN(2 first CS+E during recall)/MAXIMUM(2 last CS+E during extinction))*100)
Measured: Baseline
Main functional neuroimaging measure (activation maps for contrast CS+E versus CS-during recall phase,OCD patients versus healthy subjects)
ventro medial prefrontal cortex (vmPFC) activation during recall phase
Measured: Baseline (all subjects)
Secondary behavioral measure (learning- conditioning index, OCD patients pre and post treatment)
Equation: MEAN(all CS+ during conditioning)-MEAN(all CS- during conditioning)
Measured: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Secondary behavioral measure (learning- conditioning index, OCD patients versus healthy subjects)
Equation: MEAN(all CS+ during conditioning)-MEAN(all CS- during conditioning)
Measured: Baseline (all subjects)
Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients pre and post treatment)
Equation: MEAN(first two CS+U during renewal)-MEAN(first two CS+U during recall)
Measured: 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)
Equation: MEAN(first two CS+U during renewal)-MEAN(first two CS+U during recall)
Measured: Baseline (all subjects)
Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients pre and post treatment)
Gain in amygdala activation during conditioning for CS+ presentations
Measured: 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)
Gain in amygdala activation during conditioning for CS+ presentations
Measured: 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)
Alternative activations (OCD patients versus controls), regions other than the vmPFC, activated with CS+ presentations during recall
Measured: 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)
Alternative activations (OCD patients post treatment compared with baseline), regions other than the vmPFC, activated with CS+E presentations during recall
Measured: Change between baseline and 4 weeks after treatment initiation (only interventional group)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study start1 Dec 2016
- Primary completion20 Dec 2019
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obsessive-Compulsive DisorderStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 4-weeks open label trial of sertraline up to 200mg/day treatment for obsessive compulsive disorder
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juliana Belo Diniz, University of Sao Paulo
- Investigators
- Juliana B Diniz, MD, PhD, Principal investigator, Researcher
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03068429
- Sponsor's protocol ID
- 0182/11
- Acronym
- FEARCON
- Status last verified
- Apr 2021
- First submitted
- 22 Feb 2017
- Last updated
- 27 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The spreadsheet with main results will be made available along main publication
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fear Conditioning, Extinction and Recall in Healthy Subjects and in Obsessive-compulsive Disorder Patients Pre and Post Treatment With Sertraline.
- ClinicalTrials.gov ID
- NCT03068429
- Acronym / sponsor ID
- FEARCON / 0182/11
- Conditions
- Obsessive-Compulsive Disorder
- Keywords
- obsessive-compulsive disorder, fear conditioning, functional neuroimaging, sertraline
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 1 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 4-weeks open label trial of sertraline up to 200mg/day treatment for obsessive compulsive disorder
| Arm | Type | Receives |
|---|---|---|
| Sertraline open label | Experimental | Drug: Sertraline HydrochlorideSertraline hydrochloride up to 200mg/day or maximum tolerated dosage for 4-weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy controls
- -willingness to participate in research
- OCD patients
- willingness to participate in research
- main diagnosis of OCD (psychiatric clinical evaluation)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sertraline HydrochlorideAlso: sertraline 50mg, zoloftfirst 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 | Drug | Sertraline open label |
Primary outcome
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)
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
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)
10 secondary outcomes
Main behavioral measure baseline comparison (extinction retention index OCD patients versus healthy subjects)
Time frame: 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)
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)
Secondary behavioral measure (learning- conditioning index, OCD patients versus healthy subjects)
Time frame: 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)
Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients versus healthy subjects)
Time frame: 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)
Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients versus healthy subjects)
Time frame: 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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Individual participant dataSharing planned: Yes. The spreadsheet with main results will be made available along main publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juliana B Diniz, MD, PhD principal investigator
Researcher
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sertraline Hydrochloride in people with Obsessive-Compulsive Disorder, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2021.