Back to resultsCombined Treatment for Generalized Anxiety Disorder (GAD)
Primary Purpose
Generalized Anxiety Disorder
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cognitive Behavioral Therapy
Venlafaxine XR
Sponsored by
About this trial
This is an interventional treatment trial for Generalized Anxiety Disorder focused on measuring Generalized Anxiety Disorder, Cognitive Behavioral Therapy, Psychotherapy plus medication, Combined treatment
Eligibility Criteria
Inclusion Criteria:
- GAD diagnosis by structured interview
- Hamilton Anxiety Scale score of 18 or less
- Clinical Global Impressions Scale score of at least 4
- Hamilton Depression Scale score of 18 or less
- Hamilton Depression Scale suicide item score less than 2
- Use of an effective form of contraception throughout the s
Exclusion Criteria:
- Hypersensitivity to venlafaxine XR
- History of seizures
- Episode of major depressive disorder in the previous 6 months
- History of any psychotic illness, bipolar disorder, or dementia
- Substance abuse and dependence during the past 6 months
- Other anxiety disorders with the exception of social phobia as long as GAD is primary
- Regular use of anxiolytics or antidepressants within 7 days of study onset
- Use of fluoxetine or monoamine oxidase inhibitors within 28 days of study onset (low dose usage of benzodiazepines will not prevent participation)
- Use of other psychotic medication besides benzodiazepines
Sites / Locations
- University of Pennsylvania, 3535 Market Street, Suite 650
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Combined Treatment
Venlafaxine XR 75-225 mg alone
Arm Description
Patients who receive combined cognitive behavioral therapy (CBT) plus medication (venlafaxine XR, flexibly dosed between 75-225 mg/day) treatment for GAD. CBT was once/week sessions for 12 weeks. Medication continued for the full 6 months.
These patients receive only medication treatment for GAD. Patients take venlafaxine (flexibly dosed from 75-225 mg/day) as part of NCT00183274 and are assessed over a 6 month period. Medication continued for the full 6 months.
Outcomes
Primary Outcome Measures
Hamilton Anxiety Rating Scale (HAM-A)
The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment.
Secondary Outcome Measures
Hospital Anxiety Depression Scale (HAD)-Anxiety Score
The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety.
Hospital Anxiety Depression Scale (HAD)-Depression Score
The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression.
Hamilton Rating Scale for Depression (HAM-D)-17-item Score
The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment.
Clinical Global Impression (CGI)-Severity Score
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment.
Clinical Global Impression (CGI)-Improvement Score
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment.
Quality of Life Subscale of the General Health Questionnaire (GHQ)
The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health.
Penn State Worry Questionnaire (PSWQ)
The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry.
Physical Component Score of the 12-Item Short Form Survey (SF-12)
The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Mental Component Score of the 12-item Short Form Survey (SF-12)
The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Clinical Response Rate
Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase.
50 Percent or Greater Reduction in PSWQ Score
Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula "c" for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population.
Full Information
NCT ID
NCT00620776
First Posted
February 7, 2008
Last Updated
December 23, 2016
Sponsor
University of Pennsylvania
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT00620776
Brief Title
Combined Treatment for Generalized Anxiety Disorder (GAD)
Official Title
Combined Treatment for Generalized Anxiety Disorder (GAD)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to conduct a preliminary evaluation of the efficacy of combined medication and psychotherapy for generalized anxiety disorder (GAD). The general goals of the current study are to conduct a late stage treatment development study. The goal of this stage of research is to provide a preliminary answer to the question and to gather data to estimate intervention parameters (e.g., effect size, attrition rates, response rates) that would assist in planning further research.
Detailed Description
The specific aims of this study are to collect preliminary data relevant to the following hypotheses:
Primary Hypothesis: Acute phase improvement for combined cognitive behavioral therapy (CBT) plus medication will be superior to medication alone.
Secondary Hypotheses: Combined CBT plus medication will be superior to medication alone on a number of secondary outcome measures, including the core feature of GAD (worry), depressive symptoms, functional impairment, and quality of life.
Additional Exploratory Aim: We will explore the comparative relapse rates for the combined CBT plus medication treatment and the medication alone treatment condition at 6-month follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Anxiety Disorder
Keywords
Generalized Anxiety Disorder, Cognitive Behavioral Therapy, Psychotherapy plus medication, Combined treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combined Treatment
Arm Type
Experimental
Arm Description
Patients who receive combined cognitive behavioral therapy (CBT) plus medication (venlafaxine XR, flexibly dosed between 75-225 mg/day) treatment for GAD. CBT was once/week sessions for 12 weeks. Medication continued for the full 6 months.
Arm Title
Venlafaxine XR 75-225 mg alone
Arm Type
Active Comparator
Arm Description
These patients receive only medication treatment for GAD. Patients take venlafaxine (flexibly dosed from 75-225 mg/day) as part of NCT00183274 and are assessed over a 6 month period. Medication continued for the full 6 months.
Intervention Type
Behavioral
Intervention Name(s)
Cognitive Behavioral Therapy
Intervention Description
This cognitive behavioral therapy for GAD has a cognitive restructuring component and an applied relaxation component. Patients will be educated about the nature of anxiety and be trained in the recognition and monitoring of situational, physiological, cognitive, and behavioral cues associated with anxious responding. They will be guided through copings skill rehearsals in addition to imaginal and in vivo exposure to anxiety cues. This cognitive behavioral treatment will consist of 1 to 1.5 hour sessions of psychotherapy, which will be held once weekly over a period of 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Venlafaxine XR
Other Intervention Name(s)
Effexor extended release
Intervention Description
Venlafaxine XR, 75-225 mg/d, oral administration. 14 days at 75 mg/d, 150 mg/d for the remaining 6 months, 225 mg/3 for patients unimproved at week 6, tapered at 75 mg/week (this intervention is provided by protocol 709012).
Primary Outcome Measure Information:
Title
Hamilton Anxiety Rating Scale (HAM-A)
Description
The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment.
Time Frame
Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Secondary Outcome Measure Information:
Title
Hospital Anxiety Depression Scale (HAD)-Anxiety Score
Description
The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety.
Time Frame
Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Title
Hospital Anxiety Depression Scale (HAD)-Depression Score
Description
The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression.
Time Frame
Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Title
Hamilton Rating Scale for Depression (HAM-D)-17-item Score
Description
The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment.
Time Frame
Data collected as part of protocol 709012 at baseline, week 12, and week 24
Title
Clinical Global Impression (CGI)-Severity Score
Description
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment.
Time Frame
Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Title
Clinical Global Impression (CGI)-Improvement Score
Description
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment.
Time Frame
Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Title
Quality of Life Subscale of the General Health Questionnaire (GHQ)
Description
The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health.
Time Frame
Data collected as part of protocol 709012 at baseline, week 12, and week 24
Title
Penn State Worry Questionnaire (PSWQ)
Description
The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry.
Time Frame
Data collected as part of protocol 709012 at baseline, week 12, and week 24
Title
Physical Component Score of the 12-Item Short Form Survey (SF-12)
Description
The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time Frame
Data collected as part of protocol 709012 at baseline, week 12, and week 24
Title
Mental Component Score of the 12-item Short Form Survey (SF-12)
Description
The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time Frame
Data collected as part of protocol 709012 at baseline, week 12, and week 24
Title
Clinical Response Rate
Description
Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase.
Time Frame
Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Title
50 Percent or Greater Reduction in PSWQ Score
Description
Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula "c" for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population.
Time Frame
Data collected as part of protocol 709012 at baseline, week 12, and week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
GAD diagnosis by structured interview
Hamilton Anxiety Scale score of 18 or less
Clinical Global Impressions Scale score of at least 4
Hamilton Depression Scale score of 18 or less
Hamilton Depression Scale suicide item score less than 2
Use of an effective form of contraception throughout the s
Exclusion Criteria:
Hypersensitivity to venlafaxine XR
History of seizures
Episode of major depressive disorder in the previous 6 months
History of any psychotic illness, bipolar disorder, or dementia
Substance abuse and dependence during the past 6 months
Other anxiety disorders with the exception of social phobia as long as GAD is primary
Regular use of anxiolytics or antidepressants within 7 days of study onset
Use of fluoxetine or monoamine oxidase inhibitors within 28 days of study onset (low dose usage of benzodiazepines will not prevent participation)
Use of other psychotic medication besides benzodiazepines
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Crits-Christoph, PhD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania, 3535 Market Street, Suite 650
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Combined Treatment for Generalized Anxiety Disorder (GAD)
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