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D-Cycloserine to Enhance Cognitive Behavioral Therapy (CBT) for Acrophobia

Primary Purpose

Phobic Disorders

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Individual Cognitive Behavioral Therapy (CBT)
D-Cycloserine
Placebo
Sponsored by
Southern Methodist University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phobic Disorders focused on measuring Phobias, Anxiety Disorders, D-Cycloserine, Phobic Disorders, Mental Disorders, Heights, Acrophobia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Males or females 18-65 years of age with a psychiatric diagnosis of acrophobia defined by DSM-IV criteria.
  2. Willingness and ability to comply with the requirements of the study protocol.

Exclusion Criteria:

  1. A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, mental retardation or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance (amphetamines, benzodiazepines, barbiturates, cocaine metabolites, marijuana, narcotics, and sedative hypnotics) abuse or dependence or alcohol abuse or dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation.
  2. Patients with posttraumatic stress disorder and panic disorder within the past 6 months are excluded. Entry of patients with other mood or anxiety disorders will be permitted in order to increase accrual of a clinically relevant sample. Patients with significant suicidal ideation (MADRS item 10 score > 3) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
  3. Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment.
  4. Significant personality dysfunction likely to interfere with study participation.
  5. Serious medical illness or instability for which hospitalization may be likely within the next year.
  6. Patients with a current or past history of seizures.
  7. Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months).
  8. Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of acrophobia is excluded. Prohibited psychotherapy includes CBT therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and provides management skills. General supportive therapy initiated > 3 months prior is acceptable.
  9. Prior non-response to adequately delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment) will exclude participants from the study.
  10. Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.
  11. Patients receiving isoniazid.
  12. Patients unable to understand study procedures and participate in the informed consent process.

Sites / Locations

  • Southern Methodist University

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Sugar Pill

D-Cycloserine

Arm Description

Participants will receive placebo augmented cognitive behavioral therapy

Participants will receive D-Cycloserine augmented cognitive behavioral therapy

Outcomes

Primary Outcome Measures

Acrophobia Questionnaire With Avoidance (AAVQ)
Self-report measure that assesses fear and avoidance of a variety of heights situations. This questionnaire (Cohen, 1977) describes 20 situations and assesses levels of avoidance (0-3) and anxiety (0-6). These scales widely used measure of acrophobia with adequate retest reliability (r = .82-.86) and validity (Baker et al., 1973). Higher scores indicate higher levels of avoidance/anxiety (i.e., worse outcome). All subscales are summed for a total score. AAVQ will be assessed at each visit throughout the 2 month protocol. The minimum score is 0, the maximum is 90.

Secondary Outcome Measures

Attitudes Towards Heights Questionnaire (ATHQ)
Self-report measures that assesses thoughts and feelings towards heights situations. This questionnaire (Abelson and Curtis, 1989) includes six heights situations and assesses attitudes toward these situations using a 0-10 scale. Higher scores indicate a worse outcome and total scores are summed over subscales. Will be assessed at each visit throughout the 2 month protocol. The minimum score is a 0; the maximum is a 60.
Clinical Global Improvement Scale (CGI)
Clinician-rated measure of improvement in acrophobia symptoms and severity. Will be assessed at each visit throughout the 2 month protocol. The CGI-S and CGI-I are widely used measures of global psychopathology severity and improvement initially developed for the study of psychotropic drugs (Guy, 1970). In order to obtain CGI ratings, the therapists (blind to study condition) interviewed the participant and used the SCID (including the specific phobia module) as well as the additional measures of acrophobia symptoms (BAT, AAQ, AAVQ, and ATHQ). In the current study, response was defined as either "very much improved" or "much improved" on CGI-I (score ≤ 2). Remission was defined as either "normal" or "minimally ill" on CGI-S (score ≤ 2). The minimum rating is a 1 and the highest is a 7. Lower scores indicate a better outcome.
Behavioral Avoidance Test (BAT)
During the initial screen, at post-treatment, and at follow-up, participants underwent a behavioral avoidance test in the virtual reality height environment. Participants reported on a 0-100 scale (100 being the most intense fear) their SUDS for floors 1, 2, 3, 4, 9, 19 of the virtual glass elevator and balconies. This test has been used successfully as a measure of treatment gains in previous studies of acrophobia research (Ressler et al., 2004). For the outcome analyses, we included the level of fear reported at the highest floor of the virtual elevator environment (19th floor). Higher scores indicate a worse outcome.

Full Information

First Posted
April 9, 2010
Last Updated
January 18, 2013
Sponsor
Southern Methodist University
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1. Study Identification

Unique Protocol Identification Number
NCT01102803
Brief Title
D-Cycloserine to Enhance Cognitive Behavioral Therapy (CBT) for Acrophobia
Official Title
Evaluation of the Effects of Post-Session Administration of D-cycloserine On Exposure Therapy Outcomes
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Southern Methodist University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to investigate the utility of post-session administration of D-cycloserine to enhance fear extinction in a sample of people with acrophobia who will be treated with CBT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phobic Disorders
Keywords
Phobias, Anxiety Disorders, D-Cycloserine, Phobic Disorders, Mental Disorders, Heights, Acrophobia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sugar Pill
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo augmented cognitive behavioral therapy
Arm Title
D-Cycloserine
Arm Type
Experimental
Arm Description
Participants will receive D-Cycloserine augmented cognitive behavioral therapy
Intervention Type
Behavioral
Intervention Name(s)
Individual Cognitive Behavioral Therapy (CBT)
Other Intervention Name(s)
CBT, DCS
Intervention Description
The aim of CBT is to help participants become more comfortable with heights situations. Participants will receive 2 sessions over two weeks of individual CBT.
Intervention Type
Drug
Intervention Name(s)
D-Cycloserine
Intervention Description
D-Cycloserine
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sugar Pill
Primary Outcome Measure Information:
Title
Acrophobia Questionnaire With Avoidance (AAVQ)
Description
Self-report measure that assesses fear and avoidance of a variety of heights situations. This questionnaire (Cohen, 1977) describes 20 situations and assesses levels of avoidance (0-3) and anxiety (0-6). These scales widely used measure of acrophobia with adequate retest reliability (r = .82-.86) and validity (Baker et al., 1973). Higher scores indicate higher levels of avoidance/anxiety (i.e., worse outcome). All subscales are summed for a total score. AAVQ will be assessed at each visit throughout the 2 month protocol. The minimum score is 0, the maximum is 90.
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Attitudes Towards Heights Questionnaire (ATHQ)
Description
Self-report measures that assesses thoughts and feelings towards heights situations. This questionnaire (Abelson and Curtis, 1989) includes six heights situations and assesses attitudes toward these situations using a 0-10 scale. Higher scores indicate a worse outcome and total scores are summed over subscales. Will be assessed at each visit throughout the 2 month protocol. The minimum score is a 0; the maximum is a 60.
Time Frame
2 months
Title
Clinical Global Improvement Scale (CGI)
Description
Clinician-rated measure of improvement in acrophobia symptoms and severity. Will be assessed at each visit throughout the 2 month protocol. The CGI-S and CGI-I are widely used measures of global psychopathology severity and improvement initially developed for the study of psychotropic drugs (Guy, 1970). In order to obtain CGI ratings, the therapists (blind to study condition) interviewed the participant and used the SCID (including the specific phobia module) as well as the additional measures of acrophobia symptoms (BAT, AAQ, AAVQ, and ATHQ). In the current study, response was defined as either "very much improved" or "much improved" on CGI-I (score ≤ 2). Remission was defined as either "normal" or "minimally ill" on CGI-S (score ≤ 2). The minimum rating is a 1 and the highest is a 7. Lower scores indicate a better outcome.
Time Frame
2 months
Title
Behavioral Avoidance Test (BAT)
Description
During the initial screen, at post-treatment, and at follow-up, participants underwent a behavioral avoidance test in the virtual reality height environment. Participants reported on a 0-100 scale (100 being the most intense fear) their SUDS for floors 1, 2, 3, 4, 9, 19 of the virtual glass elevator and balconies. This test has been used successfully as a measure of treatment gains in previous studies of acrophobia research (Ressler et al., 2004). For the outcome analyses, we included the level of fear reported at the highest floor of the virtual elevator environment (19th floor). Higher scores indicate a worse outcome.
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Males or females 18-65 years of age with a psychiatric diagnosis of acrophobia defined by DSM-IV criteria. Willingness and ability to comply with the requirements of the study protocol. Exclusion Criteria: A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, mental retardation or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance (amphetamines, benzodiazepines, barbiturates, cocaine metabolites, marijuana, narcotics, and sedative hypnotics) abuse or dependence or alcohol abuse or dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation. Patients with posttraumatic stress disorder and panic disorder within the past 6 months are excluded. Entry of patients with other mood or anxiety disorders will be permitted in order to increase accrual of a clinically relevant sample. Patients with significant suicidal ideation (MADRS item 10 score > 3) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention. Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment. Significant personality dysfunction likely to interfere with study participation. Serious medical illness or instability for which hospitalization may be likely within the next year. Patients with a current or past history of seizures. Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months). Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of acrophobia is excluded. Prohibited psychotherapy includes CBT therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and provides management skills. General supportive therapy initiated > 3 months prior is acceptable. Prior non-response to adequately delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment) will exclude participants from the study. Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment. Patients receiving isoniazid. Patients unable to understand study procedures and participate in the informed consent process.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jasper Smits, Ph.D.
Organizational Affiliation
Southern Methodist University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southern Methodist University
City
Dallas
State/Province
Texas
ZIP/Postal Code
75206
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23332511
Citation
Smits JA, Rosenfield D, Otto MW, Powers MB, Hofmann SG, Telch MJ, Pollack MH, Tart CD. D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia. Biol Psychiatry. 2013 Jun 1;73(11):1054-8. doi: 10.1016/j.biopsych.2012.12.009. Epub 2013 Jan 16.
Results Reference
derived
PubMed Identifier
23098672
Citation
Tart CD, Handelsman PR, Deboer LB, Rosenfield D, Pollack MH, Hofmann SG, Powers MB, Otto MW, Smits JA. Augmentation of exposure therapy with post-session administration of D-cycloserine. J Psychiatr Res. 2013 Feb;47(2):168-74. doi: 10.1016/j.jpsychires.2012.09.024. Epub 2012 Oct 23.
Results Reference
derived
Links:
URL
http://faculty.smu.edu/jsmits/Anxiety_Research_%26_Treatment_Program_%40_SMU/index.html
Description
SMU Anxiety Research and Treatment Program

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D-Cycloserine to Enhance Cognitive Behavioral Therapy (CBT) for Acrophobia

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