Augmentation of Psychotherapy With D-Cycloserine in Agoraphobia

Agoraphobia Clinical Trial

— Exposure-DCS  

Official title:

Augmentation of Exposure Therapy With D-Cycloserine in Patients With Agoraphobia With or Without Panic Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01928823
• Other study ID #: 221013
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2013
• Last updated: May 16, 2014
• Start date: November 2011
• Est. completion date: May 2014

Study information

• Verified date: May 2014
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Agoraphobia

Intervention

Behavioral:
• CBT
12 sessions of CBT (cognitive behavioral therapy) with psychoeducation and in-vivo exposure

Drug:
• D-Cycloserine
Administered for three times (50mg, oral) directly after exposure

Locations

Country	Name	City	State
Germany	Department of Psychiatry and Psychotherapy, Charité Campus Mitte - Universitätsmedizin Berlin	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Heart Rate Variability	Furthermore HRV during the three exposure sessions will be investigated.	Change from Baseline to follow-up (9 weeks)	No
Primary	Panic- and Agoraphobia Rating Scale (PAS)	The PAS is designed for patients with agoraphobia or panic disorder who are at least 15 years old. It can be used to determine the severity of the disorder or to examine therapeutic success. There is a self-rating and a clinician-rating version available with 14 items each, yet the items are the same in both versions. Answers are given on a five-point Likert scale from "0" to "4" with higher scores indicating a higher severity. For determination of the severity of the disorder, 13 items are summed up, only item "U" (asking if panic attacks occur expected or unexpected) is not considered, resulting in scores between 0 and 52. There are also five sub scores if only special contents are of interest: Panic attacks, agoraphobic avoidance, anticipatory anxiety, disability, and worries about health.; For the present study the German version of the questionnaire is used.	Change from Baseline to Posttreatment (5 weeks)	No
Secondary	Beck Anxiety Inventory (BAI)		Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)	No
Secondary	Clinical Global Index (CGI)		Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)	No
Secondary	Agoraphobic Cognitions, Body Sensations Questionnaire and Mobility Inventory (AKV)		Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)	No
Secondary	Anxiety Sensitivity Index (ASI)		Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)	No
Secondary	Beck Depression Inventory first revised(BDI II)		Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)	No
Secondary	Brief Symptom Inventory (BSI)		Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)	No

External Links

•   Homepage of the research group for anxiety disorders of the Charité