A Study of the Efficacy of Botox in the Treatment of Social Anxiety Disorder

• Sponsor: Daniel Lieberman (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03078270
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 7.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief 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 after injection.

Condition or Disease	Intervention/Treatment	Phase
Anxiety Disorder Social; Anxiety	Drug: botulinum toxin A; Other: Placebo	Phase 4

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

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Controlled Study of the Efficacy of Botulinum Toxin A (Botox) for the Treatment of Social Anxiety Disorder (SAD)
• Actual Study Start Date: Feb 1, 2017
• Actual Primary Completion Date: Sep 12, 2017
• Actual Study Completion Date: Sep 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Open-label 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.	Drug: botulinum toxin A; Single treatment visit for 5 injections of botulinum toxin A, 40 units (for females) and 50 units (for males)/; Other Names: Botox
Placebo Comparator: Double-Blind 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.	Drug: botulinum toxin A; Single treatment visit for 5 injections of botulinum toxin A, 40 units (for females) and 50 units (for males)/; Other Names: Botox ; Other: Placebo; single treatment visit for 5 injections of normal saline; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Efficacy of of Botulinum Toxin A Reducing Symptoms of Social Anxiety Disorder [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• primary diagnosis of social anxiety disorder

• women of childbearing potential on an acceptable form of birth control and are not pregnant or lactating

Exclusion Criteria:

• 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

• unstable medical condition

• changes in medication or psychotherapy treatment in the month prior to screening

• significant risk of committing homicide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GW University Medical Faculty Associated	Washington	District of Columbia	United States	20036

Sponsors and Collaborators

• Daniel Lieberman

Investigators

• Principal Investigator: Daniel Z Lieberman, MD, George Washington University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 8, 2016

More Information

Publications

• Finzi 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.
• Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg. 2006 May;32(5):645-9; discussion 649-50.
• Magid 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.
• 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.
• Wollmer MA, de Boer C, Kalak N, Beck J, Götz T, Schmidt T, Hodzic M, Bayer U, Kollmann T, Kollewe K, Sönmez 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.

• Responsible Party: Daniel Lieberman, Physician Faculty Director, George Washington University
• ClinicalTrials.gov Identifier: NCT03078270
• Other Study ID Numbers: 041641
• First Posted: Mar 13, 2017
• Last Update Posted: Jan 23, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Daniel Lieberman, Physician Faculty Director, George Washington University: social anxiety; botulinum toxin; botox
• Additional relevant MeSH terms: Anxiety Disorders; Phobia, Social; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Open-label	Double-Blind
Arm/Group Description	4 participants were recruited for the open-label study.	0 participants were recruited for the double-blind, comparison study.
Period Title: Overall Study
STARTED	4	0
COMPLETED	0	0
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Open-label	Double-Blind	Total
Arm/Group Description	4 participants were recruited with social anxiety disorder.	No participants were recruited.	Total of all reporting groups
Overall Participants	4	0	4
Age (Count of Participants)
<=18 years	0 0%	0 NaN
Between 18 and 65 years	4 100%	4 Infinity
>=65 years	0 0%	0 NaN
Sex: Female, Male (Count of Participants)
Female	3 75%	0 NaN	3 75%
Male	1 25%	0 NaN	1 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN	0 0%
Not Hispanic or Latino	4 100%	0 NaN	4 100%
Unknown or Not Reported	0 0%	0 NaN	0 0%

Outcome Measures

1. Primary Outcome

Title	Efficacy of of Botulinum Toxin A Reducing Symptoms of Social Anxiety Disorder
Description	Repeated measure at baseline, 4-weeks and 8-weeks post-injection of anxiety using the Liebowitz Social Anxiety Scale to determine treatment response.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

The study was closed before outcome measures were collected.

Arm/Group Title	Open-label	Double-Blind
Arm/Group Description	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. botulinum toxin A: Single treatment visit for 5 injections of botulinum toxin A, 40 units (for females) and 50 units (for males)/	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. botulinum toxin A: Single treatment visit for 5 injections of botulinum toxin A, 40 units (for females) and 50 units (for males)/ Placebo: single treatment visit for 5 injections of normal saline
Measure Participants	0	0

Adverse Events

Time Frame	11 months
Adverse Event Reporting Description	No adverse events were reported.
Arm/Group Title	Open-label		Double-Blind
Arm/Group Description	4 participants were recruited for the open-label study.		0 participants were recruited for the double-blind, comparison study.
All Cause Mortality
	Open-label		Double-Blind
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Serious Adverse Events
	Open-label		Double-Blind
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Open-label		Double-Blind
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.