Clinical trial NCT02473913: Milk Thistle in Trichotillomania in Children and Adults
Official title: Silymarin Treatment of Trichotillomania in Children and Adults: A Double-Blind, Placebo-Controlled, Cross-Over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Trichotillomania
Hair Pulling Disorder
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2015-06-17
Enrollment: 22
Sex: ALL
Minimum age (years): 10
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in NIMH Trichotillomania Severity Scale (NIMH-TSS) Scores
timeFrame: Baseline and 13 weeks
Secondary outcomes:
measure: Massachusetts General Hospital Hair Pulling Scale (MGH-HPS)
timeFrame: Up to 13 weeks
measure: Clinical Global Impression- Severity and Improvement (CGI)
timeFrame: Up to 13 weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: Up to 13 weeks
measure: Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: Up to 13 weeks
measure: Hamilton Depression Rating Scale (HAM-D)
timeFrame: Up to 13 weeks
measure: Trichotillomania Scale for Children/Parent (TSC-C & TSC-P)
timeFrame: Up to 13 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Jon E Grant, JD, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: