Influence of Valproic Acid on Extinction-based Therapy in Patients With Fear of Spiders.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether valproic acid in combination with fear memory reactivation is useful to enhance treatment stability of exposure therapy for specific phobia.

Detailed Description
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There will be one screening visit (visit 1), one intervention visit (visit 2) and one follow-up visit (90 days after visit 2) (visit 3). On visit 2 all participants will undergo 30 min exposure therapy in virtual reality with pre-defined spider situations. Duration for an individual participant will be at most 15 weeks depending on the time passing between screening (visit 1) and intervention visit (visit 2). Change in phobic fear to baseline (visit 1) will be assessed on 90 day follow-up (visit 3). Documentation of all study relevant source data of every study participant will be done by completing the study specific electronic case report forms (eCRF, SoSci Survey) and study specific case report forms on paper (Adverse Events, Serious Adverse Events and concomitant medication). Data in the eCRF can be validated for completeness and discrepancies automatically. An audit trail system maintains a record of initial entries and changes (reasons for changes, time and date of changes, user identification of entry and changes). Quality insurance will be done by an external site monitoring (including study progress, accuracy and completeness of eCRF, fulfillment of protocol requirements, applicable local authority regulations and investigator's obligations). Monitoring includes 100% of safety parameters, primary endpoints, informed consent documents and the Trial Master File on the Initiation Visit and on Close Out. Standard Operating Procedures to address study activities such as patient recruitment, informed consent, study interventions, data collection, data management, data analysis, and reporting for adverse events exist.

Official Title
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Randomized Placebo-controlled Phase II Study on the Influence of Valproic Acid in Combination With Reactivation of Fear Memory on the Outcome of Extinction-based Therapy in Patients With Fear of Spiders.

Conditions
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Phobia, Specific

Intervention / Treatment
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* Drug: Valproic Acid
* Drug: Placebo
* Behavioral: Fear reactivation
* Behavioral: No fear reactivation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV diagnosis of specific phobia (animal type: spider) BAT score (at screening) between 1 and 7 points Physically healthy Normotensive (90/60-140/90 mmHg) Male or female Aged between 18 and 40 years Native or fluent German-speaking Females have to be on effective birth control Exclusion Criteria: Other axis I disorder except a further comorbid phobic disorder Concurrent psychotherapy or pharmacotherapy Previous exposure-based therapy for specific phobia Parallel participation in another study Body weight less than 50kg Long-term medication intake Substance abuse 5 or more cigarettes a day and/or inability of being abstinent for at least 5 hours Pregnancy or breast-feeding Kinetosis History of coagulation disease History of gastrointestinal disease Laboratory exclusion criteria: clinically relevant deviation of laboratory values (blood count, blood chemistry, coagulation status, liver and pancreas enzymes, electrolytes) from normal range

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valproic Acid and fear reactivation<br>This group will receive once a combination of 500mg Valproic Acid (oral solution) and fear reactivation before exposure therapy. | Drug: Valproic Acid<br>* Once oral administration of 500mg before exposure therapy.<br>* Other names: Orfiril®;Behavioral: Fear reactivation<br>* Fear reactivation before exposure therapy.<br>|
| Active Comparator: Valproic Acid and no fear reactivation<br>This group will receive once 500mg Valproic Acid (oral solution) before exposure therapy. | Drug: Valproic Acid<br>* Once oral administration of 500mg before exposure therapy.<br>* Other names: Orfiril®;Behavioral: No fear reactivation<br>* No fear reactivation before exposure therapy.<br>|
| Placebo Comparator: Placebo and fear reactivation<br>This group will receive once a combination of Placebo (oral solution) and fear reactivation before exposure therapy. | Drug: Placebo<br>* Once oral administration of 500mg before exposure therapy.<br>Behavioral: Fear reactivation<br>* Fear reactivation before exposure therapy.<br>|
| Placebo Comparator: Placebo and no fear reactivation<br>This group will receive once Placebo (oral solution) before exposure therapy. | Drug: Placebo<br>* Once oral administration of 500mg before exposure therapy.<br>Behavioral: No fear reactivation<br>* No fear reactivation before exposure therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in performance in Behavioral Approach Test (BAT) in real-life (in vivo) |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in performance in BAT in virtual reality (in virtuo) |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention | 
| Change in subjective reactions in BAT in virtual reality (in virtuo) |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention | 
| Change in psychophysiological reactions in BAT in virtual reality (in virtuo) |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention | 
| Change in subjective reactions to fear-related picture cue presentation quantified by visual analog scales (VAS) for valence, arousal and fear |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention | 
| Change in psychophysiological reactions to fear-related picture cue presentation quantified by electrodermal activity (EDA), heart rate (HR), startle response |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention | 
| Performance in working and recognition memory of pictures task |  | Follow up (visit 3: 90 days after visit 2: intervention) | 
| Valence, arousal, and mood ratings of pictures of working and recognition memory of pictures task |  | Follow up (visit 3: 90 days after visit 2: intervention) | 
| Change in strength of phobic fear quantified by self-report questionnaires |  | Baseline (7-21 days before visit 2: intervention), intervention (visit 2: 7-21 days after visit 1: baseline) and follow up (visit 3: 90 days after visit 2: intervention) | 
| Change in mood and state-anxiety quantified by self-report questionnaires |  | Baseline (7-21 days before visit 2: intervention), intervention (visit 2: 7-21 days after visit 1: baseline) and follow up (visit 3: 90 days after visit 2: intervention) | 
| Change in performance during exposure in virtuo quantified by eye tracking |  | Intervention (visit 2: 7-21 days after visit 1: baseline) | 
| Change in subjective reactions during exposure in virtuo quantified by subjective units of discomfort (SUD) ratings |  | Intervention (visit 2: 7-21 days after visit 1: baseline) | 
| Change in psychophysiological reactions during exposure in virtuo quantified by EDA and HR |  | Intervention (visit 2: 7-21 days after visit 1) | 
| Change in clinical relevance of phobic symptoms measured by Diagnostic Interview for Psychiatric Disorders (DIPS), section for specific phobia |  | Baseline (visit 1: 7-21 days before visit 2: intervention) and follow up (visit 3: 90 days after visit 2: intervention) |