Augmentation of Psychotherapy With D-Cycloserine in Agoraphobia (Exposure-DCS)

This study has been completed.
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Prof. Dr. Andreas Ströhle, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01928823
First received: July 26, 2013
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Agoraphobia
Behavioral: CBT
Drug: D-Cycloserine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Augmentation of Exposure Therapy With D-Cycloserine in Patients With Agoraphobia With or Without Panic Disorder

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Panic- and Agoraphobia Rating Scale (PAS) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Beck Anxiety Inventory (BAI) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks) ] [ Designated as safety issue: No ]
  • Clinical Global Index (CGI) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks) ] [ Designated as safety issue: No ]
  • Agoraphobic Cognitions, Body Sensations Questionnaire and Mobility Inventory (AKV) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks) ] [ Designated as safety issue: No ]
  • Anxiety Sensitivity Index (ASI) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks) ] [ Designated as safety issue: No ]
  • Beck Depression Inventory first revised(BDI II) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks) ] [ Designated as safety issue: No ]
  • Brief Symptom Inventory (BSI) [ Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks) ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Heart Rate Variability [ Time Frame: Change from Baseline to follow-up (9 weeks) ] [ Designated as safety issue: No ]
    Furthermore HRV during the three exposure sessions will be investigated.


Enrollment: 73
Study Start Date: November 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: D-Cycloserine + CBT
Patients receiving CBT (cognitive behavioral therapy) and D-Cycloserine (3 times, 50 mg, oral) directly after an exposure
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
Other Name: "Seromycin" by Eli Lilly and Company
Placebo Comparator: Placebo + CBT
Patients receiving CBT (cognitive behavioral therapy) and a placebo pill (3 times, looking identical to the DCS pill) directly after an exposure
Behavioral: CBT
12 sessions of CBT (cognitive behavioral therapy) with psychoeducation and in-vivo exposure

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01928823

Locations
Germany
Department of Psychiatry and Psychotherapy, Charité Campus Mitte - Universitätsmedizin Berlin
Berlin, Germany, 10117
Sponsors and Collaborators
Charite University, Berlin, Germany
German Federal Ministry of Education and Research
Investigators
Principal Investigator: Andreas Ströhle, Prof. Dr. Charite University, Berlin, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Dr. Andreas Ströhle, assistant medical director, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01928823     History of Changes
Other Study ID Numbers: 221013
Study First Received: July 26, 2013
Last Updated: May 16, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
agoraphobia
panic disorder
D-Cycloserine
DCS
exposure
cognitive behavioral therapy
CBT
augmentation

Additional relevant MeSH terms:
Agoraphobia
Anxiety Disorders
Mental Disorders
Cycloserine
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antibiotics, Antitubercular
Antimetabolites
Antitubercular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014