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Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder

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ClinicalTrials.gov Identifier: NCT00282828
Recruitment Status : Completed
First Posted : January 27, 2006
Results First Posted : October 14, 2013
Last Update Posted : October 14, 2013
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Mark H. Pollack, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE January 25, 2006
First Posted Date  ICMJE January 27, 2006
Results First Submitted Date  ICMJE April 22, 2013
Results First Posted Date  ICMJE October 14, 2013
Last Update Posted Date October 14, 2013
Study Start Date  ICMJE March 2006
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2013)
Rates of Remission (LSAS≤30) After 12 Weeks of Randomized Treatment During Phase II, Among Phase I Non-responders [ Time Frame: Measured at Week 22 (Endpoint) ]
The Liebowitz Social Anxiety Scale (LSAS) is a 24-item scale assessing fear and avoidance in social and performance situations; it is widely used in studies of pharmacological treatment of Generalized Social Anxiety Disorder (GSAD). Scores on the LSAS range from 0 to 144, with higher scores indicating greater pathology.
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2006)
  • Remission rates less than 30 on the Liebowitz Social Anxiety Scale (LSAS); measured at Week 20
  • Post-treatment social phobia severity as defined by endpoint LSAS scores; measured at Week 20 or last-observation
Change History Complete list of historical versions of study NCT00282828 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2013)
Post-treatment Social Phobia Severity as Defined by Endpoint LSAS Scores [ Time Frame: Change from Week 10 to Week 22 ]
The Liebowitz Social Anxiety Scale (LSAS) is a 24-item scale assessing fear and avoidance in social and performance situations; it is widely used in studies of pharmacological treatment of Generalized Social Anxiety Disorder (GSAD). We analyzed the overall change in LSAS (last Phase II LSAS minus Week 10 LSAS). Higher numbers reflect greater drops in social anxiety disorder severity. Scores on the LSAS range from 0 to 144, with higher scores indicating greater pathology.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2006)
Treatment response; measured at Week 10
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder
Official Title  ICMJE Improving Outcomes in Pharmacotherapy of Social Phobia
Brief Summary This study will compare the effectiveness of either adding clonazepam or placebo to standard treatment or switching to venlafaxine in treating generalized social anxiety disorder in individuals who have not responded to treatment with sertraline.
Detailed Description

Generalized social anxiety disorder (GSAD) is one of the most common psychiatric disorders, and often causes significant distress and dysfunction in affected individuals. Although currently available treatments for GSAD are effective, most individuals have residual symptoms after initial psychosocial or psychopharmacologic intervention. Further treatment is necessary for such individuals, but sufficient research has not been done to guide clinicians on what the safest and most effective next step may be. This study will compare the effectiveness of either combining clonazepam or placebo with sertraline or completely switching to venlafaxine in treating GSAD in individuals who have not responded to treatment with sertraline. This study will also examine predictors of treatment response, including factors such as age at disease onset, duration of illness, comorbidities, and genes that influence serotonin and catecholamine metabolism.

Participants in this double-blind study will first partake in an initial 10-week phase in which they will be treated with sertraline. Participants who do not respond to sertraline treatment will proceed to phase two of the study, in which they will be randomly assigned to one of three treatment groups. One group will receive both sertraline and clonazepam, another group will receive both sertraline and placebo, and the third group will receive only venlafaxine. All treatments will continue for 12 weeks. Sertraline and venlafaxine are both FDA-approved for the treatment of GSAD. Clonazepam is widely used for the treatment of anxiety, but is not FDA-approved for the treatment of GSAD. All participants will attend weekly study visits at Weeks 1, 2, 4, 6, 8, and 10. Participants who continue into phase two will attend weekly study visits at Weeks 11-14, 16, 18, 20, and 22. Symptom remission rates and post-treatment social phobia severity will be assessed at Week 22.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Social Phobia
Intervention  ICMJE
  • Drug: Sertraline
  • Drug: Venlafaxine
  • Drug: Placebo
  • Drug: Clonazepam
Study Arms  ICMJE
  • Experimental: Sertraline & Clonazepam

    Phase I non-responders randomized to this group remained on sertraline at the same dose level as at entry into Phase 2 with the addition of clonazepam up to 3.0mg per day.

    Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 0.5mg of clonazepam per day in order to remain in the study.

    Interventions:
    • Drug: Sertraline
    • Drug: Clonazepam
  • Experimental: Venlafaxine

    Phase I non-responders randomized to this group switched to venlafaxine with flexible titration up to 225 mg per day.

    Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 75 mg venlafaxine per day in order to remain in the study.

    Intervention: Drug: Venlafaxine
  • Experimental: Sertraline & Placebo

    Phase I non-responders randomized to this group remained on sertraline at the same dose level as at entry into Phase 2 with the addition of placebo.

    Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 1 capsule of placebo per day in order to remain in the study.

    Interventions:
    • Drug: Sertraline
    • Drug: Placebo
Publications * Pollack MH, Van Ameringen M, Simon NM, Worthington JW, Hoge EA, Keshaviah A, Stein MB. A double-blind randomized controlled trial of augmentation and switch strategies for refractory social anxiety disorder. Am J Psychiatry. 2014 Jan;171(1):44-53. doi: 10.1176/appi.ajp.2013.12101353.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 14, 2012)
397
Original Enrollment  ICMJE
 (submitted: January 25, 2006)
490
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Primary psychiatric diagnosis of GSAD as defined by DSM-IV criteria and a score above 60 on the LSAS
  • Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

  • Clinically significant abnormalities found upon physical examination, electrocardiogram, and laboratory tests
  • History of more than two unsuccessful, adequate treatment trials, indicated by a lack of response to over 10 weeks of any of the following: SSRIs (e.g., 40 mg of paroxetine or its equivalent per day); benzodiazepine (e.g. at least 2.5 mg of clonazepam per day) plus antidepressant (adequate dose as above); monoamine oxidase inhibitors (e.g., 60 mg of phenelzine or its equivalent per day); or a single failed trial of over 10 weeks of venlafaxine ( at least 150 mg per day)
  • Pregnant or breastfeeding
  • Simultaneous use of other psychotropic medications, with the exception of psychostimulants to treat ADHD; participants must discontinue regular benzodiazepine or antidepressant therapy at least two weeks (5 weeks for fluoxetine) prior to study entry; beta-blockers must be discontinued unless they are indicated medically (e.g., for hypertension)
  • DSM-IV diagnosis of any of the following: lifetime history of schizophrenia or any other psychosis, mental retardation, organic medical disorder, bipolar disorder, or obsessive compulsive disorder; eating disorder in the past 6 months; alcohol or substance abuse in the past 3 months or dependence within the past 6 months (entry of participants with major depression, dysthymia, panic disorder, generalized anxiety disorder, or post-traumatic stress disorder will be permitted if the social anxiety disorder is judged to be the predominant disorder)
  • Significant suicidal ideation as indicated by a score greater than 3 on the Montgomery-Asberg Depression Rating Scale or suicidal behaviors within 6 months prior to study entry
  • Significant personality dysfunction that could interfere with study participation
  • Serious medical illness or instability for which hospitalization may be likely during the study
  • Seizure disorders, with the exception of a childhood history of isolated, non-recurrent febrile seizures
  • Any concurrent psychotherapy initiated within 3 months of study entry, or ongoing psychotherapy of any duration directed specifically toward treatment of GSAD (prohibited psychotherapy includes cognitive behavioral therapy or psychodynamic therapy that focuses on exploring specific, dynamic causes of the phobic symptomatology and that provides management skills; general supportive therapy for more than 3 months is acceptable)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00282828
Other Study ID Numbers  ICMJE R01MH070919( U.S. NIH Grant/Contract )
R01MH070919 ( U.S. NIH Grant/Contract )
PA-01-123
DSIR 83-ATAS
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mark H. Pollack, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Mark H. Pollack, MD Massachusetts General Hospital
Principal Investigator: Murray B. Stein, MD, MPH University of California San Deigo
Principal Investigator: Michael Van Ameringen, MD, FRCPC Anxiety Disorders Clinic McMaster University Medical Centre
PRS Account Massachusetts General Hospital
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP