Anxiety Disorder SocialPhase 4NCT03078270
A Study of the Efficacy of Botox in the Treatment of Social Anxiety Disorder
A Phase 4 study testing botulinum toxin A in people with Anxiety Disorder Social and Anxiety, run by Daniel Lieberman at 1 site in United States.
Trial summary
The goal of this study is to see whether Botox is an effective treatment for social anxiety disorder (SAD). Participants will complete two short surveys on depression and anxiety symptoms, receive a one-time injection of Botox, and complete the depression and anxiety survey 4 weeks after injection and again at 8 weeks… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Anxiety Disorder Social, Anxiety
- What is being tested?
- botulinum toxin A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2017to 12 Sep 2017
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- primary diagnosis of social anxiety disorder
- women of childbearing potential on an acceptable form of birth control and are not pregnant or lactating
Who cannot join
- has ever been treated with botulinum toxin A
- has another Axis I diagnosis within in the 6-months prior to screening
- history of substance abuse within 2-months of screening
- current or recent suicidality
- scoring greater than 2 on Beck Depression Inventory (BDI) suicidality question
- psychotic or bipolar disorder
Show all 9Show fewer
- unstable medical condition
- changes in medication or psychotherapy treatment in the month prior to screening
- significant risk of committing homicide
Trial locations and contacts
1 site in 1 country.
United States1 site
GW University Medical Faculty Associated
Washington D.C., District of Columbia, 20036
About this study
Official title: A Controlled Study of the Efficacy of Botulinum Toxin A (Botox) for the Treatment of Social Anxiety Disorder (SAD)
The goal of this study is to see whether Botox is an effective treatment for social anxiety disorder (SAD). Participants will complete two short surveys on depression and anxiety symptoms, receive a one-time injection of Botox, and complete the depression and anxiety survey 4 weeks after injection and again at 8 weeks after injection.
Read the detailed description
The use of botulinum toxin A to correct glabellar frown lines is an effective and popular cosmetic procedure with more than 1 million treatments per year in the United States alone (Carruthers, A.). Botulinum toxin type A marketed commercially as BOTOX® Cosmetic (Botox), is produced from fermentation of Hall strain Clostridium botulinum type A grown in a medium containing casein hydrolysate, glucose, and yeast extract, intended for intramuscular use.
Botox blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, Botox produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by Botox.
Botox is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients ≤ 65 years of age.
Botox is contraindicated in the presence of infection at the proposed injection site(s) and in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.
Depression
The first open label trial of Botox to the glabellar muscle complex to treat unipolar depression was published in 2006. Since that time, three randomized double blind placebo-controlled trials were conducted to assess the efficacy of Botox treatment of the glabellar muscle complex in major depression. All three studies showed a response rate of 50 to 60%, and the remission rate of approximately one-third. To date, no clinical trials of Botox have been conducted in SAD.
Social Anxiety Disorder (SAD)
Social anxiety disorder (SAD) is a common psychiatric condition marked by persistent fear and anxiety of one or more social or performance situations. The lifetime prevalence of the disorder is 12%, and leads to significant morbidity for those affected. The only FDA approved treatments for SAD have response rates of 40 to 60 %, and remission rates of 20%. Therefore, there is a real need for the development of new and effective treatments for SAD.
Patients suffering from SAD either avoid situational triggers or endure intense anxiety and distress, leading to an impaired social life in either scenario. SAD is characterized by an overactive anxiety pathway with a perceptual and cognitive bias towards threat.
The amygdala, a limbic region with multiple projections to cortical and subcortical regions, is thought to be critically involved in the regulation of emotion, with a general role in directing attention to affectively salient stimuli, recruiting and coordinating cortical arousal for optimizing sensory and perceptual processing of ambiguous or novel stimuli.. A tight link between fear and the amygdala has been suggested. Fear related neuronal circuits involving the amygdala are thought to play a role in the generation of social withdrawal, fear, and anxiety.
Recently, two studies have linked botulinum toxin A treatment of the frown with down-regulation of amygdala activity. Patients who received botulinum toxin A injections into their frown muscles had decreased activity in the amygdala and its coupling with brain stem activity when mimicking angry facial expressions. Further research has confirmed that amygdala activity in response to angry faces was decreased when the frown muscles were paralyzed by botulinum toxin A injection. Furthermore, amygdala activity returned to its original state after the effects of the botulinum toxin A injection had worn off, confirming that botulinum toxin A reversibly severed afferent feedback from the corrugator muscle to the amygdala.
Given that SAD patients show abnormal patterns of amygdalar activation after viewing emotional faces, we believe that there is a good likelihood that some of the symptoms of SAD will improve after botulinum toxin A treatment of the frown.
- Conditions
- Anxiety Disorder Social, Anxiety
- Being tested
- botulinum toxin A, Placebo
- Keywords
- social anxiety, botulinum toxin, botox
- Medical subject headings
- Phobia, Social, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
botulinum toxin ADrug
Also called Botox
Single treatment visit for 5 injections of botulinum toxin A, 40 units (for females) and 50 units (for males)/
PlaceboOther
Also called Saline
single treatment visit for 5 injections of normal saline
| Study group | Role | What they receive |
|---|---|---|
| Open-label | Other | 10 participants will be recruited for an open-label study. All will receive the active medication and complete depression and anxiety surveys at baseline, 4-weeks, and 8-weeks post injection. All participants will receive botulinum toxin A. Receives: Drug: botulinum toxin A |
| Double-Blind | Placebo comparator | 30 participants will be recruited for a double-blind, comparison study. Participants will be randomized to the active or control groups. Each will receive an injection (active medication or placebo) and will complete a depression and anxiety survey at baseline, 4-weeks and 8-weeks post injection. Participants in the active group will receive botulinum toxin A; participants in the control group will receive a placebo. Receives: Drug: botulinum toxin A; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of of Botulinum Toxin A Reducing Symptoms of Social Anxiety Disorder
Repeated measure at baseline, 4-weeks and 8-weeks post-injection of anxiety using the Liebowitz Social Anxiety Scale to determine treatment response.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2017
- Study start1 Feb 2017
- Primary completion12 Sep 2017
- Study completion12 Sep 2017
Why it stopped: study terminated due to low recruitment
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 (5)Papers the sponsor has linked to this study.
- Other trials for Anxiety Disorder SocialStudies of the same condition, open and under way.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daniel Lieberman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Daniel Lieberman, George Washington University
- Investigators
- Daniel Z Lieberman, MD, Principal investigator, George Washington University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03078270
- Sponsor's protocol ID
- 041641
- Status last verified
- Jan 2019
- First submitted
- 21 Feb 2017
- Last updated
- 23 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data sharing is not planned on being shared with other investigators
Publications
Reichenberg JS, Hauptman AJ, Robertson HT, Finzi E, Kruger TH, Wollmer MA, Magid M. Botulinum toxin for depression: Does patient appearance matter? J Am Acad Dermatol. 2016 Jan;74(1):171-173.e1. doi: 10.1016/j.jaad.2015.08.051. No abstract available.
PubMed 26702796Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg. 2006 May;32(5):645-9; discussion 649-50. doi: 10.1111/j.1524-4725.2006.32136.x.
PubMed 16706759Finzi E, Rosenthal NE. Emotional proprioception: Treatment of depression with afferent facial feedback. J Psychiatr Res. 2016 Sep;80:93-96. doi: 10.1016/j.jpsychires.2016.06.009. Epub 2016 Jun 16.
PubMed 27344227Magid M, Reichenberg JS, Poth PE, Robertson HT, LaViolette AK, Kruger TH, Wollmer MA. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Aug;75(8):837-44. doi: 10.4088/JCP.13m08845.
PubMed 24910934Wollmer MA, de Boer C, Kalak N, Beck J, Gotz T, Schmidt T, Hodzic M, Bayer U, Kollmann T, Kollewe K, Sonmez D, Duntsch K, Haug MD, Schedlowski M, Hatzinger M, Dressler D, Brand S, Holsboer-Trachsler E, Kruger TH. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012 May;46(5):574-81. doi: 10.1016/j.jpsychires.2012.01.027. Epub 2012 Feb 24.
PubMed 22364892
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled Study of the Efficacy of Botulinum Toxin A (Botox) for the Treatment of Social Anxiety Disorder (SAD)
- ClinicalTrials.gov ID
- NCT03078270
- Acronym / sponsor ID
- 041641
- Conditions
- Anxiety Disorder Social, Anxiety
- Keywords
- social anxiety, botulinum toxin, botox
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study terminated due to low recruitment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Daniel LiebermanUniversity, hospital or other
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 12 Sep 2017 (actual)
- Study completion
- 12 Sep 2017 (actual)
- First posted
- 13 Mar 2017 (actual)
- Results
- Posted 23 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to see whether Botox is an effective treatment for social anxiety disorder (SAD). Participants will complete two short surveys on depression and anxiety symptoms, receive a one-time injection of Botox, and complete the depression and anxiety survey 4 weeks after injection and again at 8 weeks after injection.
Detailed description
The use of botulinum toxin A to correct glabellar frown lines is an effective and popular cosmetic procedure with more than 1 million treatments per year in the United States alone (Carruthers, A.). Botulinum toxin type A marketed commercially as BOTOX® Cosmetic (Botox), is produced from fermentation of Hall strain Clostridium botulinum type A grown in a medium containing casein hydrolysate, glucose, and yeast extract, intended for intramuscular use.
Botox blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, Botox produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by Botox.
Botox is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients ≤ 65 years of age.
Botox is contraindicated in the presence of infection at the proposed injection site(s) and in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.
Depression
The first open label trial of Botox to the glabellar muscle complex to treat unipolar depression was published in 2006. Since that time, three randomized double blind placebo-controlled trials were conducted to assess the efficacy of Botox treatment of the glabellar muscle complex in major depression. All three studies showed a response rate of 50 to 60%, and the remission rate of approximately one-third. To date, no clinical trials of Botox have been conducted in SAD.
Social Anxiety Disorder (SAD)
Social anxiety disorder (SAD) is a common psychiatric condition marked by persistent fear and anxiety of one or more social or performance situations. The lifetime prevalence of the disorder is 12%, and leads to significant morbidity for those affected. The only FDA approved treatments for SAD have response rates of 40 to 60 %, and remission rates of 20%. Therefore, there is a real need for the development of new and effective treatments for SAD.
Patients suffering from SAD either avoid situational triggers or endure intense anxiety and distress, leading to an impaired social life in either scenario. SAD is characterized by an overactive anxiety pathway with a perceptual and cognitive bias towards threat.
The amygdala, a limbic region with multiple projections to cortical and subcortical regions, is thought to be critically involved in the regulation of emotion, with a general role in directing attention to affectively salient stimuli, recruiting and coordinating cortical arousal for optimizing sensory and perceptual processing of ambiguous or novel stimuli.. A tight link between fear and the amygdala has been suggested. Fear related neuronal circuits involving the amygdala are thought to play a role in the generation of social withdrawal, fear, and anxiety.
Recently, two studies have linked botulinum toxin A treatment of the frown with down-regulation of amygdala activity. Patients who received botulinum toxin A injections into their frown muscles had decreased activity in the amygdala and its coupling with brain stem activity when mimicking angry facial expressions. Further research has confirmed that amygdala activity in response to angry faces was decreased when the frown muscles were paralyzed by botulinum toxin A injection. Furthermore, amygdala activity returned to its original state after the effects of the botulinum toxin A injection had worn off, confirming that botulinum toxin A reversibly severed afferent feedback from the corrugator muscle to the amygdala.
Given that SAD patients show abnormal patterns of amygdalar activation after viewing emotional faces, we believe that there is a good likelihood that some of the symptoms of SAD will improve after botulinum toxin A treatment of the frown.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open-label | Other | Drug: botulinum toxin A10 participants will be recruited for an open-label study. All will receive the active medication and complete depression and anxiety surveys at baseline, 4-weeks, and 8-weeks post injection. All participants will receive botulinum toxin A. |
| Double-Blind | Placebo comparator | Drug: botulinum toxin A, Other: Placebo30 participants will be recruited for a double-blind, comparison study. Participants will be randomized to the active or control groups. Each will receive an injection (active medication or placebo) and will complete a depression and anxiety survey at baseline, 4-weeks and 8-weeks post injection. Participants in the active group will receive botulinum toxin A; participants in the control group will receive a placebo. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- primary diagnosis of social anxiety disorder
- women of childbearing potential on an acceptable form of birth control and are not pregnant or lactating
Key exclusion criteria (9 listed)
- has ever been treated with botulinum toxin A
- has another Axis I diagnosis within in the 6-months prior to screening
- history of substance abuse within 2-months of screening
- current or recent suicidality
- scoring greater than 2 on Beck Depression Inventory (BDI) suicidality question
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 |
|---|---|---|
| botulinum toxin AAlso: BotoxSingle treatment visit for 5 injections of botulinum toxin A, 40 units (for females) and 50 units (for males)/ | Drug | Double-Blind, Open-label |
| PlaceboAlso: Salinesingle treatment visit for 5 injections of normal saline | Other | Double-Blind |
Primary outcome
Efficacy of of Botulinum Toxin A Reducing Symptoms of Social Anxiety Disorder
Time frame: 2 months
Repeated measure at baseline, 4-weeks and 8-weeks post-injection of anxiety using the Liebowitz Social Anxiety Scale to determine treatment response.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26702796Reichenberg JS, Hauptman AJ, Robertson HT, Finzi E, Kruger TH, Wollmer MA, Magid M. Botulinum toxin for depression: Does patient appearance matter? J Am Acad Dermatol. 2016 Jan;74(1):171-173.e1. doi: 10.1016/j.jaad.2015.08.051. No abstract available.
- Background: PubMed 16706759Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg. 2006 May;32(5):645-9; discussion 649-50. doi: 10.1111/j.1524-4725.2006.32136.x.
- Background: PubMed 27344227Finzi E, Rosenthal NE. Emotional proprioception: Treatment of depression with afferent facial feedback. J Psychiatr Res. 2016 Sep;80:93-96. doi: 10.1016/j.jpsychires.2016.06.009. Epub 2016 Jun 16.
- Background: PubMed 24910934Magid M, Reichenberg JS, Poth PE, Robertson HT, LaViolette AK, Kruger TH, Wollmer MA. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Aug;75(8):837-44. doi: 10.4088/JCP.13m08845.
- Background: PubMed 22364892Wollmer MA, de Boer C, Kalak N, Beck J, Gotz T, Schmidt T, Hodzic M, Bayer U, Kollmann T, Kollewe K, Sonmez D, Duntsch K, Haug MD, Schedlowski M, Hatzinger M, Dressler D, Brand S, Holsboer-Trachsler E, Kruger TH. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012 May;46(5):574-81. doi: 10.1016/j.jpsychires.2012.01.027. Epub 2012 Feb 24.
- Individual participant dataSharing planned: No. Data sharing is not planned on being shared with other investigators
Related trials for Anxiety Disorder Social
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Recruiting
Bonding Before Birth: A mHealth Intervention for First-time Expectant Couples
Anxiety, Pregnancy
Recruiting
Comprehensive Assessment of Rehabilitation Experience Using the SAFE Scale
Caregiver Anxiety, Acquired Brain Injury
Not yet recruiting
Online Study on the Impact of a Self-Help Tool for Social Anxiety
Social Anxiety
Active, not recruiting
Targeting Social Function in Anxiety and Eating Disorders
Eating Disorders, Anorexia Nervosa
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.
Daniel Z Lieberman, MD principal investigator
George Washington University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing botulinum toxin A in people with Anxiety Disorder Social and Anxiety, run by Daniel Lieberman at 1 site in United States.
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 9 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: stopped early, as of the sponsor's last update on 23 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 23 Jan 2019). 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?
Efficacy of of Botulinum Toxin A Reducing Symptoms of Social Anxiety Disorder (time frame: 2 months). 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 NCT03078270, which also lists 5 linked publications.
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 23 Jan 2019.