Clinical trial NCT01928823: Augmentation of Psychotherapy With D-Cycloserine in Agoraphobia
Official title: Augmentation of Exposure Therapy With D-Cycloserine in Patients With Agoraphobia With or Without Panic Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Agoraphobia
Keywords: agoraphobia
panic disorder
D-Cycloserine
DCS
exposure
cognitive behavioral therapy
CBT
augmentation
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2013-08-27
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Since decades, D-Cycloserine (DCS, drug class: Oxazolidinone) is proven to be an effective antibiotic agent in the treatment of tuberculosis. Furthermore it takes action in the central nervous system as an partial agonist on NMDA receptors. Because of glutamate mediated neuronal long-term potentiation in long-term memory DCS has an augmenting effect on emotional learning, as it occurs in exposure therapy of anxiety disorders. In this context we use DCS in addition to exposure therapy as a part of cognitive behavioral therapy (CBT) in patients suffering from agoraphobia with or without panic disorder. Thereby DCS is applicated oral as a capsule of 50mg, on three consecutive therapy sessions.

Detailed description: The present study is a multicenter study with two participating institutions: The "Klinik für Psychiatrie und Psychotherapie, Charité - Universitätsmedizin Berlin" and the "ZPHU - Zentrum für Psychotherapie am Institut für Psychologie, Humboldt-Universität zu Berlin". It is a randomized, placebo-controlled and double blind study with agoraphobic patients receiving a manualized cognitive behavioral therapy. The randomization and blindness refers to medication with an antibiotic called D-Cycloserine: One group receives D-Cycloserine after exposure sessions and the other group is treated with a placebo. The aim is to find out, whether or not D-Cycloserine augments psychotherapy outcome when administered after an exposure. Altogether, 78 patients will be treated. Before therapy, all patients receive a clinical examination to ensure that no contraindications for participating (like cardiac defects or serious central nervous system diseases) are present. In the following diagnostic sessions therapists conduct standardized assessments and after four diagnostic sessions therapy starts. All patients receive six therapy sessions, whereof three consist of exposures. When exposures are successful, D-Cycloserine or Placebo is administered afterwards. At the last therapy session another clinical examination to control several parameters is conducted. One month after therapy, two follow-up sessions with assessments take place.

Eligibility criteria: Inclusion Criteria:

* written consent (as per AMG §40 (1) 3b)
* diagnosis of agoraphobia; severity of the disorder due to the CGI should at least be "moderately ill"
* age: 18-75 years
* negative pregnancy test for premenopausal women and safe contraception (Pearlindex \< 1) during the study
* accessibility (geographical vicinity) for treatment and follow-up
* Compliance of the patient

Exclusion Criteria:

* Known overreaction after taking of D-Cycloserine
* Actual pharmacotherapy with ethionamides and/ or isoniazide
* Judicial or regulatory hospitalization in a mental institution (as per AMG §40 (1) 4)
* Severe psychiatric disorder like schizophrenia, addiction or dementia
* acute suicidal tendency
* epilepsy or other diseases concerning the CNS (e.g. brain tumor, encephalitis)
* internal disease like severe hypertension, cardiac insufficiency, cardiac arrhythmia, severe dysfunction of liver or kidney, insulin-dependent diabetes mellitus or disorders of the hematopoiesis
* lactation
* changes in a psychopharmacotherapy or discontinuation of a pretreatment with psychoactive drugs less than 4 weeks previous to the begin of the study
* disturbance of the day and night rhythm
* disorder-specific psychotherapy
* participation in another AMG-study during the last month previous to the inclusion in the study or during the participation in this study

Primary outcomes:
measure: Panic- and Agoraphobia Rating Scale (PAS)
timeFrame: Change from Baseline to Posttreatment (5 weeks)
Secondary outcomes:
measure: Beck Anxiety Inventory (BAI)
timeFrame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
measure: Clinical Global Index (CGI)
timeFrame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
measure: Agoraphobic Cognitions, Body Sensations Questionnaire and Mobility Inventory (AKV)
timeFrame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
measure: Anxiety Sensitivity Index (ASI)
timeFrame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
measure: Beck Depression Inventory first revised(BDI II)
timeFrame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
measure: Brief Symptom Inventory (BSI)
timeFrame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
Other outcomes:
measure: Heart Rate Variability
timeFrame: Change from Baseline to follow-up (9 weeks)
Locations:
city: Berlin
country: Germany
facility: Department of Psychiatry and Psychotherapy, Charité Campus Mitte - Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Andreas Ströhle, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: