- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00282828
Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder
Improving Outcomes in Pharmacotherapy of Social Phobia
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 3Z5
- McMaster University Medical Centre Anxiety Disorders Clinic
-
-
-
-
California
-
La Jolla, California, United States, 92093
- University of California San Diego
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02116
- Center for Anxiety and Traumatic Stress Disorders
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
|
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. |
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Measured at Week 22 (Endpoint)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Change from Week 10 to Week 22
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- 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
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Anxiety Disorders
- Phobia, Social
- Phobic Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- GABA Modulators
- GABA Agents
- Anticonvulsants
- Antidepressive Agents, Second-Generation
- Serotonin and Noradrenaline Reuptake Inhibitors
- Sertraline
- Venlafaxine Hydrochloride
- Clonazepam
Other Study ID Numbers
- R01MH070919 (U.S. NIH Grant/Contract)
- DSIR 83-ATAS (NIMH Program Class Code)
- PA-01-123
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Social Phobia
-
San Diego State UniversityNational Institute of Mental Health (NIMH)CompletedSocial Anxiety Disorder | Social PhobiaUnited States
-
Umeå UniversityUppsala UniversityCompleted
-
Umeå UniversityCompleted
-
Stanford UniversityNational Institute of Mental Health (NIMH)CompletedSocial PhobiaUnited States
-
University of MinnesotaAstraZenecaCompletedSocial PhobiaUnited States
-
Modum BadCompleted
-
VU University of AmsterdamCompletedSocial Anxiety Disorder | Social PhobiaNetherlands
-
McMaster UniversityHamilton Health Sciences Corporation; Janssen-Ortho Inc., CanadaTerminated
-
Pherin Pharmaceuticals, Inc.CompletedSocial Anxiety Disorder | Social PhobiaUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States