Social PhobiaPhase 4NCT00282828
Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder
A Phase 4 study testing Sertraline, Venlafaxine and Clonazepam in people with Social Phobia, run by Massachusetts General Hospital at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Social Phobia
- What is being tested?
- Sertraline, Venlafaxine and Clonazepam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 397 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Mar 2006to Dec 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Center for Anxiety and Traumatic Stress Disorders
Boston, Massachusetts, 02116
University of California San Diego
La Jolla, California, 92093
Canada1 site
McMaster University Medical Centre Anxiety Disorders Clinic
Hamilton, Ontario, L8N 3Z5
About this study
Official title: Improving Outcomes in Pharmacotherapy of Social Phobia
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.
Read the 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.
- Conditions
- Social Phobia
- Being tested
- Sertraline, Venlafaxine, Placebo, Clonazepam
- Keywords
- Social Anxiety Disorder, Pharmacotherapy, Genetics, Treatment Refractory
- Medical subject headings
- Phobia, Social
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
VenlafaxineDrug
PlaceboDrug
ClonazepamDrug
| Study group | Role | What they receive |
|---|---|---|
| Sertraline & Clonazepam | Experimental | 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. Receives: Drug: Sertraline; Drug: Clonazepam |
| Venlafaxine | Experimental | 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. Receives: Drug: Venlafaxine |
| Sertraline & Placebo | Experimental | 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. Receives: Drug: Sertraline; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of Remission (LSAS≤30) After 12 Weeks of Randomized Treatment During Phase II, Among Phase I Non-responders
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: Measured at Week 22 (Endpoint)
Secondary outcomes (1)
Post-treatment Social Phobia Severity as Defined by Endpoint LSAS Scores
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.
Measured: Change from Week 10 to Week 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2006 (estimated)
- Study startMar 2006
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Social PhobiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 397 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Mark H. Pollack, Massachusetts General Hospital
- Investigators
- Mark H. Pollack, MD, Principal investigator, Massachusetts General HospitalMurray B. Stein, MD, MPH, Principal investigator, University of California San DeigoMichael Van Ameringen, MD, FRCPC, Principal investigator, Anxiety Disorders Clinic McMaster University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00282828
- Sponsor's protocol ID
- R01MH070919
- Other IDs
- R01MH070919, PA-01-123, DSIR 83-ATAS
- Status last verified
- Aug 2013
- First submitted
- 25 Jan 2006
- Last updated
- 14 Oct 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 24399428
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Outcomes in Pharmacotherapy of Social Phobia
- ClinicalTrials.gov ID
- NCT00282828
- Acronym / sponsor ID
- R01MH070919
- Conditions
- Social Phobia
- Keywords
- Social Anxiety Disorder, Pharmacotherapy, Genetics, Treatment Refractory
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 397 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Mar 2006
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 27 Jan 2006 (estimated)
- Results
- Posted 14 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sertraline & Clonazepam | Experimental | Drug: Sertraline, Drug: ClonazepamPhase 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. |
| Venlafaxine | Experimental | Drug: VenlafaxinePhase 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. |
| Sertraline & Placebo | Experimental | Drug: Sertraline, Drug: PlaceboPhase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sertraline | Drug | Sertraline & Clonazepam, Sertraline & Placebo |
| Venlafaxine | Drug | Venlafaxine |
| Placebo | Drug | Sertraline & Placebo |
| Clonazepam | Drug | Sertraline & Clonazepam |
Primary outcome
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.
1 secondary outcome
Post-treatment Social Phobia Severity as Defined by Endpoint LSAS Scores
Time frame: Change from Week 10 to Week 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24399428Pollack 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.
- Click here for the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital websiteLink provided by the sponsor.
- Click here for the Anxiety Disorders Association of America websiteLink provided by the sponsor.
- Please click here for UCSD Anxiety and Traumatic Stress Disorders Research ProgramLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark H. Pollack, MD principal investigator
Massachusetts General Hospital
Murray B. Stein, MD, MPH principal investigator
University of California San Deigo
Michael Van Ameringen, MD, FRCPC principal investigator
Anxiety Disorders Clinic McMaster University Medical Centre
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sertraline, Venlafaxine and Clonazepam in people with Social Phobia, run by Massachusetts General Hospital at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00282828, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2013.