Phobic Disorders
Conditions
Keywords
Phobias, Anxiety Disorders, D-Cycloserine, Phobic Disorders, Mental Disorders, Heights, Acrophobia
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.
Interventions
BEHAVIORALIndividual Cognitive Behavioral Therapy (CBT)
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.
DRUGD-Cycloserine
D-Cycloserine
DRUGPlacebo
Sugar Pill
Sponsors
Southern Methodist University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acrophobia Questionnaire With Avoidance (AAVQ) | 2 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Attitudes Towards Heights Questionnaire (ATHQ) | 2 months | 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) | 2 months | 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) | 2 months | 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. |
Countries
United States
Participant flow
Recruitment details
Participants (N = 29; Mean age = 33.38) with acrophobia were recruited from Southern Methodist University and the greater Dallas area from 2009 to 2011.
Pre-assignment details
76 individuals were assessed for eligibility, of which 47 were excluded due to not having a diagnosis of acrophobia (n=37) or declining participation (n=10). 29 individuals were randomized and no participants were excluded after enrollment but prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Sugar Pill Participants will receive sugar pill placebo augmented cognitive behavioral therapy | 14 |
| D-Cycloserine Participants will receive D-Cycloserine (50mg) augmented cognitive behavioral therapy | 15 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline to Post-Treatment | Lost to Follow-up | 3 | 0 |
| Post to Follow-Up | Lost to Follow-up | 1 | 3 |
Baseline characteristics
| Characteristic | Sugar Pill | D-Cycloserine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 15 Participants | 29 Participants |
| Age Continuous | 37.71 years STANDARD_DEVIATION 16.81 | 29.33 years STANDARD_DEVIATION 14.67 | 33.8 years STANDARD_DEVIATION 15.74 |
| Region of Enrollment United States | 14 participants | 15 participants | 29 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 29 | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Primary
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.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DCS+CBT Treatment | Acrophobia Questionnaire With Avoidance (AAVQ) | 9.00 units on a scale | Standard Deviation 7.41 |
| Placebo+CBT Treatment | Acrophobia Questionnaire With Avoidance (AAVQ) | 12.38 units on a scale | Standard Deviation 9.72 |
Secondary
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.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DCS+CBT Treatment | Attitudes Towards Heights Questionnaire (ATHQ) | 45.67 units on a scale | Standard Deviation 8.53 |
| Placebo+CBT Treatment | Attitudes Towards Heights Questionnaire (ATHQ) | 47.71 units on a scale | Standard Deviation 12.98 |
Secondary
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.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DCS+CBT Treatment | Behavioral Avoidance Test (BAT) | 29.73 units on a scale | Standard Deviation 25.67 |
| Placebo+CBT Treatment | Behavioral Avoidance Test (BAT) | 35.55 units on a scale | Standard Deviation 25.18 |
Secondary
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.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DCS+CBT Treatment | Clinical Global Improvement Scale (CGI) | 2.27 units on a scale | Standard Deviation 0.96 |
| Placebo+CBT Treatment | Clinical Global Improvement Scale (CGI) | 2.00 units on a scale | Standard Deviation 0.89 |