Milk Thistle in Trichotillomania in Children and Adults

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT02473913
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 66.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The goal of the proposed study is to evaluate the efficacy and safety of silymarin (milk thistle) in children and adults with trichotillomania. The hypothesis to be tested is that silymarin will be more effective and well tolerated in children and adults with trichotillomania compared to placebo. The proposed study will provide needed data on the treatment of a disabling disorder that currently lacks a clearly effective treatment.

Condition or Disease	Intervention/Treatment	Phase
Trichotillomania; Hair Pulling Disorder	Drug: Milk Thistle; Drug: Placebo	Phase 2

Detailed Description

Pathological hair-pulling, trichotillomania, has been defined as repetitive, intentionally performed pulling that causes noticeable hair loss and results in clinically significant distress or functional impairment. Trichotillomania appears relatively common with an estimated prevalence between 1-3%. Data on the pharmacological treatment of trichotillomania is limited to case reports and conflicting double-blind studies of serotonin reuptake inhibitors. One positive double-blind study of N-acetyl cysteine in adults was not successful when examined for children and adolescents. Available data on the treatment of trichotillomania in children are therefore limited.

Silymarin, a flavonoid and a member of the Asteraceae family, is extracted from the seeds of milk thistle (Silybum marianum) and is known to have antioxidative and anti-apoptotic properties. Furthermore, it has been demonstrated that its anti-oxidative activity is related to the scavenging of free radicals and activation of anti-oxidative defenses: increases in cellular glutathione content and superoxide dismutase activity. Milk thistle has been used for a range of psychiatric disorders including methamphetamine abuse and obsessive compulsive disorder. The flavonoid complex silymarin in preclinical studies has been found to increase serotonin and dopamine levels in the cortex. In the frontal cortex one of the functions of dopamine is to increase the signal to noise ratio, increased dopamine correlating with increased frontal performance. Studies have shown that the higher cortical dopamine levels are associated with improved frontal cortical cognitive performance. Cortical inhibition is felt to be the basis for top-down control of motivated behaviors. A recent randomized controlled study with milk thistle was conducted in Iran Thirty five participants with moderate OCD were randomly assigned to 200 mg of milk thistle leaf extract or 10 mg of fluoxetine three times daily for eight weeks. Results revealed no significant difference in treatment effects between milk thistle and fluoxetine from baseline to endpoint as both interventions provided a highly significant reduction in symptoms. Silymarin or Milk Thistle may therefore offer promise for the treatment of individuals with trichotillomania.

The current pilot study examines the tolerability and efficacy of milk thistle in the treatment of trichotillomania in children and adults. The investigators hypothesize that milk thistle will reduce the severity of symptoms related to trichotillomania and improve patients' overall functioning.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Silymarin Treatment of Trichotillomania in Children and Adults: A Double-Blind, Placebo-Controlled, Cross-Over Study
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Milk Thistle Each subject will have a 6 week treatment phase with milk thistle.	Drug: Milk Thistle; Other Names: Silymarin
Placebo Comparator: Placebo 6 week placebo phase before or after milk thistle phase depending on randomization.	Drug: Placebo; Other Names: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. Change in NIMH Trichotillomania Severity Scale (NIMH-TSS) Scores [Baseline and 13 weeks]

   The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the NIMH-Trichotillomania Symptom Severity Scale (NIMH-TSS). The change in scores from baseline to after 13 weeks will be assessed. The NIMH-TSS consists of 5 questions related to the following aspects of TTM: average time spent pulling, time spent pulling on the previous day, resistance to urges, resulting distress and daily interference. NIMH-TSS scores range from 0 to 25, with higher scores indicating higher severity.

Secondary Outcome Measures

1. Massachusetts General Hospital Hair Pulling Scale (MGH-HPS) [Up to 13 weeks]

   The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the MGH-Hair Pulling Scale (MGH-HPS). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The MGH-HPS is a self report scale that assesses severity of Trichotillomania in the past week. There are seven total items each rated for severity from 0 to 4. Higher scores indicate higher symptom severity.

2. Clinical Global Impression- Severity and Improvement (CGI) [Up to 13 weeks]

   The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the CGI. At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The CGI-Severity is rated on a 7-point scale, with the severity of illness ranging from 1 (normal) through 7 (among the most severely ill patients). CGI-Change scores range from 1 (very much improved) through 7 (very much worse).

3. Sheehan Disability Scale (SDS) [Up to 13 weeks]

   The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the Sheehan Disability Scale (SDS). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The scale itself assesses the level of functional impairment from trichotillomania (or target disorder). The subject is asked to rank the extent to which work/school, family life/home responsibilities, or social life are impaired by their symptoms on a scale from 0 (not at all) to 10 (extremely). The three numerical ratings can then be summed to produce a single measure of global functional impairment from 0 (unimpaired) to 30 (highly impaired).

4. Hamilton Anxiety Rating Scale (HAM-A) [Up to 13 weeks]

   The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the Hamilton Anxiety Rating Scale (HAM-A), a 14 item scale. At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.

5. Hamilton Depression Rating Scale (HAM-D) [Up to 13 weeks]

   The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the Hamilton Depression Rating Scale (HAM-D). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. Classification of symptoms are scored as follows: 0 - absent: 1 - doubtful or trivial: 2 - present. Classification of symptoms where more detail can be obtained can be expanded to: 0 - absent; 1 - mild; 2 - moderate; 3 - severe; 4 - incapacitating. In general the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe.

6. Trichotillomania Scale for Children/Parent (TSC-C & TSC-P) [Up to 13 weeks]

   The entire study for the subject will last 13 weeks. The subject will take the TSC-C (child version).The parent of the subject will fill out the TSC-P (parent version). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The scale itself assesses severity of trichotillomania and provides a sub score for severity. The severity score is produced by adding up the scores for questions 1 through 5 and dividing that sum by 5. The second sub score is on distress/impairment with questions such as "in the past week, how often did you feel like pulling your hair?". The sub score for distress/impairment is produced by adding the scores for questions 6-12 and dividing that sum by 7. The sum of both sub scores provides a total score. Total scores (ranging between 0 and 4) were compared pre treatment and post treatment. Higher scores indicate a higher severity and distress impairment score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and females ages 10-65.

2. Diagnosis of current trichotillomania (TTM) based on DSM-5 criteria and confirmed using the clinician-administered Structured Clinical Interview for DSM-5 (SCID);

3. Hair-pulling behavior within 2 weeks prior to enrollment;

4. Child able and willing to provide active assent for participation;

5. Legal guardian available to provide consent for participation.

Exclusion Criteria:

1. Infrequent hair-pulling (i.e. less than one time per week) that does not meet DSM-5 criteria for trichotillomania;

2. Unstable medical illness as determined by the investigator;

3. History of seizures;

4. Current use of stimulants coinciding with onset or exacerbation of trichotillomania symptoms or other current medications coinciding with exacerbation or onset or trichotillomania symptoms;

5. Clinically significant suicidality (defined by the Columbia Suicide Severity Rating Scale);

6. Baseline score of ≥17 on the Hamilton Depression Rating Scale (17-item HDRS);

7. Lifetime history of bipolar disorder type I or II, schizophrenia, autism, any psychotic disorder, or any substance use disorder;

8. Initiation of psychotherapy or behavior therapy within 3 months prior to study baseline;

9. Previous treatment with milk thistle;

10. Any history of psychiatric hospitalization in the past year.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Jon E Grant, JD, MD, MPH, University of Chicago

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 19, 2017
• Informed Consent Form - Feb 20, 2018

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT02473913
• Other Study ID Numbers: 15-0178
• First Posted: Jun 17, 2015
• Last Update Posted: Nov 20, 2020
• Last Verified: Nov 1, 2020

• Additional relevant MeSH terms: Trichotillomania; Silymarin

Study Results

Participant Flow

Pre-assignment Detail	This is a crossover study. Therefore, only 22 participants were technically enrolled, but they each were supposed to complete both the placebo and the Milk Thistle Arm.

Arm/Group Title	Experimental: Milk Thistle, Then Placebo	Experimetal: Placebo, Then Milk Thistle
Arm/Group Description	Participants first received Milk Thistle for 6 weeks. After a washout period of 1 week, they then received matching Placebo for 6 weeks.	Participants first received matching Placebo for 6 weeks. After a washout period of 1 week, they then received matching Milk Thistle for 6 weeks.
Period Title: Overall Study
STARTED	11	11
COMPLETED	8	8
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Milk Thistle, Then Placebo	Placebo, Then Milk Thistle	Total
Arm/Group Description	Participants first received Milk Thistle for 6 weeks. After a washout period of 1 week, they then received matching placebo for 6 weeks.	Participants first received matching placebo for 6 weeks. After a washout period of 1 week, they then received Milk Thistle for 6 weeks.	Total of all reporting groups
Overall Participants	11	11	22
Age (Count of Participants)
<=18 years	2 18.2%	2 18.2%	4 18.2%
Between 18 and 65 years	9 81.8%	9 81.8%	18 81.8%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.5 (11.5)	27.7 (11.1)	28.1 (11.1)
Sex: Female, Male (Count of Participants)
Female	11 100%	10 90.9%	21 95.5%
Male	0 0%	1 9.1%	1 4.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%	1 9.1%	2 9.1%
Not Hispanic or Latino	10 90.9%	10 90.9%	20 90.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 18.2%	2 9.1%
White	10 90.9%	7 63.6%	17 77.3%
More than one race	0 0%	1 9.1%	1 4.5%
Unknown or Not Reported	1 9.1%	1 9.1%	2 9.1%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Change in NIMH Trichotillomania Severity Scale (NIMH-TSS) Scores
Description	The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the NIMH-Trichotillomania Symptom Severity Scale (NIMH-TSS). The change in scores from baseline to after 13 weeks will be assessed. The NIMH-TSS consists of 5 questions related to the following aspects of TTM: average time spent pulling, time spent pulling on the previous day, resistance to urges, resulting distress and daily interference. NIMH-TSS scores range from 0 to 25, with higher scores indicating higher severity.
Time Frame	Baseline and 13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	17	17
Pre-Treatment	9.4 (5.4)	9.4 (5.0)
Post-Treatment	6.3 (5.3)	7.4 (5.1)

2. Secondary Outcome

Title	Massachusetts General Hospital Hair Pulling Scale (MGH-HPS)
Description	The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the MGH-Hair Pulling Scale (MGH-HPS). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The MGH-HPS is a self report scale that assesses severity of Trichotillomania in the past week. There are seven total items each rated for severity from 0 to 4. Higher scores indicate higher symptom severity.
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	17	17
Pre-Treatment	13.5 (6.8)	14.7 (7.1)
Post-Treatment	10.4 (7.6)	12.3 (6.5)

3. Secondary Outcome

Title	Clinical Global Impression- Severity and Improvement (CGI)
Description	The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the CGI. At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The CGI-Severity is rated on a 7-point scale, with the severity of illness ranging from 1 (normal) through 7 (among the most severely ill patients). CGI-Change scores range from 1 (very much improved) through 7 (very much worse).
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	16	17
Pre-Treatment	4.1 (1.0)	3.9 (0.6)
Post-Treatment	3.0 (1.4)	3.6 (0.9)

4. Secondary Outcome

Title	Sheehan Disability Scale (SDS)
Description	The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the Sheehan Disability Scale (SDS). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The scale itself assesses the level of functional impairment from trichotillomania (or target disorder). The subject is asked to rank the extent to which work/school, family life/home responsibilities, or social life are impaired by their symptoms on a scale from 0 (not at all) to 10 (extremely). The three numerical ratings can then be summed to produce a single measure of global functional impairment from 0 (unimpaired) to 30 (highly impaired).
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	17	17
Pre-Treatment	8.8 (8.0)	8.8 (4.1)
Post-Treatment	5.2 (7.8)	5.9 (7.1)

5. Secondary Outcome

Title	Hamilton Anxiety Rating Scale (HAM-A)
Description	The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the Hamilton Anxiety Rating Scale (HAM-A), a 14 item scale. At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	17	17
Pre-Treatment	4.9 (4.8)	5.1 (4.4)
Post-Treatment	2.8 (3.5)	3.4 (3.0)

6. Secondary Outcome

Title	Hamilton Depression Rating Scale (HAM-D)
Description	The entire study for the subject will last 13 weeks. Every two weeks and after the one week washout period the subject will take the Hamilton Depression Rating Scale (HAM-D). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. Classification of symptoms are scored as follows: 0 - absent: 1 - doubtful or trivial: 2 - present. Classification of symptoms where more detail can be obtained can be expanded to: 0 - absent; 1 - mild; 2 - moderate; 3 - severe; 4 - incapacitating. In general the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe.
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	17	17
Pre-Treatment	5.7 (5.1)	5.5 (4.4)
Post-Treatment	2.7 (3.3)	2.9 (3.1)

7. Secondary Outcome

Title	Trichotillomania Scale for Children/Parent (TSC-C & TSC-P)
Description	The entire study for the subject will last 13 weeks. The subject will take the TSC-C (child version).The parent of the subject will fill out the TSC-P (parent version). At each of these visits the outcome will be assessed. Pre treatment and after the one week washout period scores reported. The scale itself assesses severity of trichotillomania and provides a sub score for severity. The severity score is produced by adding up the scores for questions 1 through 5 and dividing that sum by 5. The second sub score is on distress/impairment with questions such as "in the past week, how often did you feel like pulling your hair?". The sub score for distress/impairment is produced by adding the scores for questions 6-12 and dividing that sum by 7. The sum of both sub scores provides a total score. Total scores (ranging between 0 and 4) were compared pre treatment and post treatment. Higher scores indicate a higher severity and distress impairment score.
Time Frame	Up to 13 weeks

Outcome Measure Data

Analysis Population Description

For some subjects, the scale was not filled out at follow-up visits (in error).

Arm/Group Title	Milk Thistle	Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle	6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
Measure Participants	3	3
Pre-Treatment (TSC-C)	2.9 (0.3)	2.0 (0.8)
Post-Treatment (TSC-C)	1.7 (1.1)	1.7 (0.1)
Pre-Treatment (TSC-P)	2.5 (0.2)	1.9 (0.1)
Post-Treatment (TSC-P)	1.1 (0)	2.3 (0.2)

Adverse Events

Time Frame	Adverse event data were collected at each study visit (Visits 1-8) over the subjects' study participation (13 weeks) and over the total course of the study (3 years).
Arm/Group Title	Milk Thistle		Placebo
Arm/Group Description	Each subject will have a 6 week treatment phase with milk thistle. Milk Thistle		6 week placebo phase before or after milk thistle phase depending on randomization. Placebo
All Cause Mortality
	Milk Thistle		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/21 (0%)
Serious Adverse Events
	Milk Thistle		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Milk Thistle		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/18 (33.3%)		7/21 (33.3%)
Gastrointestinal disorders
Nausea	3/18 (16.7%)	3	2/21 (9.5%)	2
Bloating	1/18 (5.6%)	1	1/21 (4.8%)	1
Abdominal Pain	0/18 (0%)	0	1/21 (4.8%)	1
Flatulence	0/18 (0%)	0	1/21 (4.8%)	1
General disorders
Dry Mouth	0/18 (0%)	0	1/21 (4.8%)	1
Nervous system disorders
Headaches	1/18 (5.6%)	1	1/21 (4.8%)	1
Insomnia	1/18 (5.6%)	1	0/21 (0%)	0

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.