The Treatment of Depression With Botulinum Type A Toxin

• Sponsor: Seton Healthcare Family (Other)
• Overall Status: Completed
• CT.gov ID: NCT01392963
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

A 24-week Randomized, Double-blind study treating people who suffer from depression who also have moderate to severe frown lines in forehead region with Botox injections. Subjects participating will have their photos taken and complete a questionnaire regarding their depression. They will see a psychiatrist at every visit who will assess their depression.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: botulinum toxin type A neurotoxin complex; Drug: Placebo	Phase 2

Detailed Description

Participants will be assigned to receive either placebo or botulinum toxin injections in the forehead

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Treatment of Depression With Botulinum Type A Toxin (Botox): A Randomized, Double Blind, Crossover Study
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Botox, Then Placebo At baseline visit (week 0) participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications. After a 3 month evaluation period, participants received a placebo injection (matching botulinum toxin) to glabella region at study visit 4 (week 12).	Drug: botulinum toxin type A neurotoxin complex; 29-40 U injection; Other Names: Botox, botulinum toxin type A (BTA) ; Drug: Placebo; 29-40 U 0.9% NaCl injection; Other Names: botulinum toxin type A neurotoxin complex matched injection
Experimental: Placebo, Then Botox At baseline visit (week 0) participants received a placebo injection (matching botulinum toxin) to glabella region. After a 3 month evaluation period, participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications at study visit 4 (week 12).	Drug: botulinum toxin type A neurotoxin complex; 29-40 U injection; Other Names: Botox, botulinum toxin type A (BTA) ; Drug: Placebo; 29-40 U 0.9% NaCl injection; Other Names: botulinum toxin type A neurotoxin complex matched injection

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Depression Symptoms on the Hamilton Depression Rating Scale 21 (HDRS-21) AT WEEK 6 [baseline and week 6]

   HDRS-21 is a validated, clinician-administered depression assessment scale. Possible scores range from 0 - 7 (within normal range or remission) 8-16 (mild depression) 17-23 (moderate depression) 24-52 (severe depression). Change = (Week 6 post injection score - baseline week 0 score). PRIMARY OUTCOME MEASURE IS THE CHANGE IN HDRS-21 SCORE AFTER WEEK 6

Secondary Outcome Measures

1. Change From Baseline (Week 0) in Depression Symptoms on the Hamilton Depression Rating Scale 21 (HDRS-21) at Week 6 (Six Weeks Post Placebo Injection at Week 0) and Week 18 (Six Weeks Post Botox Injection at Week 12) [Baseline (Week 0), Week 6, and Week 18]

   HDRS-21 is a validated, clinician-administered depression assessment scale. Possible scores range from 0 - 7 (within normal range or remission) 8-16 (mild depression) 17-23 (moderate depression) 24-52 (severe depression). Change = (Week 6/18 score - baseline week 0 score) Outcome measure is the change in HDRS-21 score 6 weeks after injection with placebo (week 0) and Botox (week 12) - HDRS-21 done at week 6 and week 18.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male/Female between the ages of 18 and 65

2. Major Depression Disorder as defined by DSM IV criteria and diagnosed by a psychiatrist. DSM (Diagnostic and Statistical Manual) IV criteria for depression are: a depressed mood or anhedonia for at least a two week period. This mood must represent a change from the person's normal mood; social, occupational, educational or other important functioning must also be negatively impaired by the change in mood. Major depressive disorder cannot be diagnosed if a person has a history of bipolar disorder or if the depressed mood is better accounted for by substance abuse or a psychotic disorder. In addition, the patient must have 5 of the following symptoms:

• Significant weight loss or weight gain.

• Insomnia or hypersomnia

• Psychomotor agitation or retardation

• Feelings of worthlessness or excessive guilt

• Poor Concentration

• Fatigue or loss of energy

• Suicidal thoughts

1. History of depression for at least 6 months

2. Initial score 14 or higher on initial Hamilton Depression rating scale.

3. Melancholic facial expressions amenable to treatment with Botox. Photos will be taken of potential participants and ranked independently by two investigators, on a scale of 1-10 based on how negative they look, 10 being the highest. Patients with an average score of 6 or above will be included in the study

Exclusion Criteria:

1. Active substance abuse

2. Bipolar Depression

3. Subjects who are pregnant, nursing or trying to become pregnant during study participation

4. Subjects who are currently on more than 3 psychiatric medications at the time of enrollment

5. Current medications used to treat depression must be stable for at least 60 days prior to enrollment

6. Previous Botox treatment

7. The Principle Investigator has determined that this study is not in the best interest of the subject and therefore the subject will not be enrolled.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seton Mind Institute: Medical Park Tower	Austin	Texas	United States	78705

Sponsors and Collaborators

• Seton Healthcare Family

Investigators

• Principal Investigator: Michelle Magid, MD, Seton Healthcare Family

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seton Healthcare Family
• ClinicalTrials.gov Identifier: NCT01392963
• Other Study ID Numbers: CR-11-021
• First Posted: Jul 13, 2011
• Last Update Posted: Jul 26, 2018
• Last Verified: Jun 1, 2018

• 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 Seton Healthcare Family: botox; depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Recruitment Details	Participants were recruited from local outpatient psychiatry and primary care practices, and through internet advertisements and media appearances.
Pre-assignment Detail	A total of 101 were screened via telephone, 39 received a face-to-face screening interview, and 30 were enrolled in the study.

Arm/Group Title	Botox, Then Placebo	Placebo, Then Botox
Arm/Group Description	At baseline visit (week 0) participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications. After a 3 month evaluation period, participants received a placebo injection (matching botulinum toxin) to glabella region at study visit 4 (week 12).	At baseline visit (week 0) participants received a placebo injection (matching botulinum toxin) to glabella region. After a 3 month evaluation period, participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications at study visit 4 (week 12).
Period Title: Week 0 (First Intervention)
STARTED	11	19
COMPLETED	11	17
NOT COMPLETED	0	2
Period Title: Week 0 (First Intervention)
STARTED	11	17
COMPLETED	11	17
NOT COMPLETED	0	0
Period Title: Week 0 (First Intervention)
STARTED	11	17
COMPLETED	9	17
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Botox, Then Placebo	Placebo, Then Botox	Total
Arm/Group Description	At baseline visit (week 0) participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications. After a 3 month evaluation period, participants received a placebo injection (matching botulinum toxin) to glabella region at study visit 4 (week 12).	At baseline visit (week 0) participants received a placebo injection (matching botulinum toxin) to glabella region. After a 3 month evaluation period, participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications at study visit 4 (week 12).	Total of all reporting groups
Overall Participants	11	19	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	19 100%	30 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 100%	17 89.5%	28 93.3%
Male	0 0%	2 10.5%	2 6.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Depression Symptoms on the Hamilton Depression Rating Scale 21 (HDRS-21) AT WEEK 6
Description	HDRS-21 is a validated, clinician-administered depression assessment scale. Possible scores range from 0 - 7 (within normal range or remission) 8-16 (mild depression) 17-23 (moderate depression) 24-52 (severe depression). Change = (Week 6 post injection score - baseline week 0 score). PRIMARY OUTCOME MEASURE IS THE CHANGE IN HDRS-21 SCORE AFTER WEEK 6
Time Frame	baseline and week 6

Outcome Measure Data

Analysis Population Description

Participants that completed all study visits were included in the analysis.

Arm/Group Title	Placebo, Then Botox	Botox, Then Placebo
Arm/Group Description	At baseline visit (week 0) participants received a placebo injection (matching botulinum toxin) to glabella region. After a 3 month evaluation period, participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications at study visit 4 (week 12). botulinum toxin type A neurotoxin complex: 29-40 U injection Placebo: 29-40 U 0.9% NaCl injection	At baseline visit (week 0) participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin. After a 3 month evaluation period, participants received a placebo injection (matching botulinum toxin) to glabella region at study visit 4 (week 12).
Measure Participants	19	11
Mean (Standard Deviation) [units on a scale]	-0.4 (4)	-12.7 (4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Then Botox, Botox, Then Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Baseline (Week 0) in Depression Symptoms on the Hamilton Depression Rating Scale 21 (HDRS-21) at Week 6 (Six Weeks Post Placebo Injection at Week 0) and Week 18 (Six Weeks Post Botox Injection at Week 12)
Description	HDRS-21 is a validated, clinician-administered depression assessment scale. Possible scores range from 0 - 7 (within normal range or remission) 8-16 (mild depression) 17-23 (moderate depression) 24-52 (severe depression). Change = (Week 6/18 score - baseline week 0 score) Outcome measure is the change in HDRS-21 score 6 weeks after injection with placebo (week 0) and Botox (week 12) - HDRS-21 done at week 6 and week 18.
Time Frame	Baseline (Week 0), Week 6, and Week 18

Outcome Measure Data

Analysis Population Description

2 patients in the placebo first group dropped out at crossover and were not included in the 18 week assessment

Arm/Group Title	Placebo, Then Botox (Week 6)	Placebo, Then Botox (Week 18)
Arm/Group Description	Group received placebo injection at week 0 of study followed by a Botox injection at week 12. HDRS-21 scores were done six weeks after each injection (week 6 and week 18).	Group received placebo injection at week 0 of study followed by a Botox injection at week 12. HDRS-21 scores were done six weeks after each injection (week 6 and week 18).
Measure Participants	19	17
Mean (Standard Deviation) [units on a scale]	-0.4 (3)	-8.4 (3)

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Botox, Then Placebo		Placebo, Then Botox
Arm/Group Description	At baseline visit (week 0) participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications. After a 3 month evaluation period, participants received a placebo injection (matching botulinum toxin) to glabella region at study visit 4 (week 12).		At baseline visit (week 0) participants received a placebo injection (matching botulinum toxin) to glabella region. After a 3 month evaluation period, participants received an injection of clostridium botulinum toxin type A neurotoxin complex (Allergan; total injection of 29-40 U) in the glabella region according to standard protocols of cosmetic botulinum toxin applications at study visit 4 (week 12).
All Cause Mortality
	Botox, Then Placebo		Placebo, Then Botox
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/19 (0%)
Serious Adverse Events
	Botox, Then Placebo		Placebo, Then Botox
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Botox, Then Placebo		Placebo, Then Botox
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/19 (0%)

Limitations/Caveats

93% of participants were female. This did not allow for statistical analysis based on gender. Although statistically significant, the sample size of this study was small.

More Information

Certain Agreements

All Principal Investigators ARE 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.