Clincosm LogoSign in Get a demo

Dronabinol in Trichotillomania and Other Body Focused Repetitive Behaviors

Sponsor
University of Chicago (Other)
Overall Status
Completed
CT.gov ID
NCT03530800
Collaborator
(none)
50
Enrollment
1
Location
2
Arms
37
Actual Duration (Months)
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of the proposed study is to evaluate the efficacy and safety of dronabinol in trichotillomania and other body-focused repetitive behaviors such as skin-picking disorder. 50 subjects with DSM-5 trichotillomania or skin-picking disorder will receive 10 weeks of double-blind dronabinol or placebo. The hypothesis to be tested is that dronabinol will be effective and well tolerated in patients with trichotillomania and/or skin-picking disorder compared to placebo. The proposed study will provide needed data on the treatment of disabling disorders that currently lacks a clearly effective treatment.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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. Although discussed in the medical literature for over one hundred years, and affecting all strata of society, there have been no epidemiological studies detailing how common trichotillomania is and there are no clear treatment approaches for everyone with trichotillomania. Behavioral therapy is generally regarded as the first-line treatment but trained therapists are difficult to find. In addition, there is no medication currently approved by the Food and Drug Administration for trichotillomania. Trichotillomania is related clinically to other BFRBs, specifically skin picking disorder. In fact, it appears that trichotillomania and skin picking disorder may in fact share a common neurobiology. Other BFRBs such as skin ppicking disorder also lack any agreed upon medication intervention, but evidence suggests that both skin picking disorder and trichotillomania may respond to the same interventions.

The Trichotillomania Impact Project survey showed that only 15% of adults in the community with trichotillomania reported experiencing significant improvement with treatment of their symptoms. This may be because of the ongoing difficulty of finding a therapist experienced in trichotillomania treatments. More than 55% of persons in this survey believed that their clinician did not have sufficient knowledge of the disorder, and less than one-third were receiving evidence-based treatments for trichotillomania.

A recent meta-analytic study of randomized treatment trials in adults demonstrated that behavioral treatments, mainly habit reversal therapy, have the greatest efficacy in treatment of trichotillomania. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used treatment for adults with trichotillomania, despite evidence that their efficacy is no greater than placebo.

Instead of using SSRIs, the investigators conducted an open-label study of dronabinol a synthetic form of tetrahydrocannabinol (THC) approved by the FDA as an appetite stimulant for people with AIDS and antiemetic for people receiving chemotherapy, in 14 women with trichotillomania and found that 9 (64.3%) responded to treatment and that the mean effective dose was 11.6 ± 4.1 mg/day.

A recent study using diffusion tensor imaging demonstrated that both trichotillomania and skin-picking subjects exhibited significantly reduced fractional anisotropy in anterior cingulate, presupplementary motor area, and temporal cortices. These data suggest that the disorganization of white matter tracts in motor habit generation and suppression may underlie the pathophysiology of these disorders. Neurochemically, motor habits may rely partially on the endocannabinoid system. CB1 receptors are highly expressed in the basal ganglia nuclei, the hippocampus, cerebellum, and neocortex and are implicated in attenuating glutamatergic exocitotoxic damage by suppressing the neuronal release of glutamate via inhibition of calcium channels. The activation of CB1 receptors reduces glutamate release in the dorsal and ventral striatum [possibly through an interaction with brain-derived neurotrophic factor], thereby modulating neurotransmission in the basal ganglia and mesolimbic reward system . Stress-induced anxious behavior has been associated with the loss of CB1 receptor function in the striatum.

Glutamatergic dysfunction has been implicated in the pathophysiology of trichotillomania. Pharmacotherapies, such as dronabinol, that target excessive glutamatergic drive through its effects on CB! Receptors may, therefore, be expected to correct the underlying pathophysiology and symptoms of trichotillomania.

In the USA, dronabinol is FDA-approved for the treatment of anorexia associated with weight loss in patients with AIDS and nausea and vomiting associated with cancer chemotherapy. In our previous study examining dronabinol for trichotillomania, doses between 5 and 15mg/day were well tolerated and beneficial. This lack of significant side effects is consistent with other studies of dronabinol where it has been associated primarily with central nervous system-related adverse events (for example, confusion, dizziness, euphoria, and somnolence), but these adverse events are generally mild to moderate in severity and generally reversible upon dose modification.

Given the serious personal consequences associated with trichotillomania, and the likelihood of success of dronabinol in treating the disorder, the aim of the present study was to examine the efficacy and safety of dronabinol vs placebo in adults with trichotillomania using a double-blind, placebo-controlled design.

The investigators hypothesize that dronabinol will be more effective than placebo in reducing the frequency of hair pulling and in improving overall psychosocial functioning after 10 weeks of treatment when compared to baseline.

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Placebo-Controlled Study of Dronabinol in Trichotillomania and Other Body Focused Repetitive Behaviors
Actual Study Start Date :
Oct 1, 2018
Actual Primary Completion Date :
Jul 20, 2021
Actual Study Completion Date :
Nov 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Dronabinol

Subjects will receive dronabinol 5mg once daily for two weeks, 5mg twice daily for the subsequent two weeks, and 5mg three times daily for the final six weeks. Dose escalations will only be done if the investigator deems necessary.

Drug: Dronabinol
Dronabinol for 10 weeks (5mg per day first 2 weeks, 10mg per day second two weeks, 15mg per day last six weeks)
Other Names:
  • Marinol

    		•
    Placebo Comparator: Placebo

    Subjects will receive placebo for 10 weeks weeks.

    Drug: Placebo
    Placebo for 10 weeks

    Outcome Measures

    Primary Outcome Measures

    1. NIMH Trichotillomania Symptom Severity Scale (NIMH-TSS) [Assessed every two weeks up to 10 weeks, baseline data reported]

      The entire study lasts 10 weeks. Every two weeks subjects will take the NIMH-TSS. The change in scores from baseline to after 10 weeks will be assessed. The scale itself assesses severity of trichotillomania symptoms. The NIMH-TSS score ranges from 0 to 20, with 0 being no symptoms and 20 being the most severe.

    2. Skin Picking Symptom Assessment Scale (SP-SAS) [Assessed every two weeks up to 10 weeks, baseline reported]

      The entire study lasts 10 weeks. Every two weeks subjects will take the SP-SAS. The change in scores from baseline to after 10 weeks will be assessed. The scale itself assesses severity of skin-picking symptoms. The SP-SAS score ranges from 0 to 48, with 0 being no symptoms and 48 being the most severe.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • current DSM-5 trichotillomania

    • ability to understand and sign the consent form

    Exclusion Criteria:

    • Unstable Medical illness based on history of clinically significant abnormalities on baseline physical examination

    • Current pregnancy or lactation, or inadequate contraception in women of childbearing potential

    • Subjects considered an immediate suicide risk based on the Columbia Suicide Severity Rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)

    • Past 12-month DSM-5 psychiatric disorder other than trichotillomania

    • Illegal substance use based on urine toxicology screening

    • Use of any other psychotropic medication (except a PRN hypnotic)

    • Previous treatment with dronabinol

    • Cognitive impairment that interferes with the capacity to understand and self administer medication or provide written informed consent

    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)

    More Information

    Publications

    Responsible Party:
    University of Chicago
    ClinicalTrials.gov Identifier:
    NCT03530800
    Other Study ID Numbers:
    • IRB18-0542
    First Posted:
    May 21, 2018
    Last Update Posted:
    Jun 2, 2022
    Last Verified:
    May 1, 2022
    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
    Additional relevant MeSH terms:
    Trichotillomania
    Dronabinol

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dronabinol Placebo
    Arm/Group Description Subjects will receive dronabinol 5mg once daily for two weeks, 5mg twice daily for the subsequent two weeks, and 5mg three times daily for the final six weeks. Dose escalations will only be done if the investigator deems necessary. Dronabinol: Dronabinol for 10 weeks (5mg per day first 2 weeks, 10mg per day second two weeks, 15mg per day last six weeks) Subjects will receive placebo for 10 weeks weeks. Placebo: Placebo for 10 weeks
    Period Title: Overall Study
    STARTED 25 25
    COMPLETED 14 16
    NOT COMPLETED 11 9

    Baseline Characteristics

    Arm/Group Title Dronabinol Placebo Total
    Arm/Group Description Subjects will receive dronabinol 5mg once daily for two weeks, 5mg twice daily for the subsequent two weeks, and 5mg three times daily for the final six weeks. Dose escalations will only be done if the investigator deems necessary. Dronabinol: Dronabinol for 10 weeks (5mg per day first 2 weeks, 10mg per day second two weeks, 15mg per day last six weeks) Subjects will receive placebo for 10 weeks weeks. Placebo: Placebo for 10 weeks Total of all reporting groups
    Overall Participants 25 25 50
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    33.04
    (12.48)
    28.36
    (7.27)
    30.7
    (10.38)
    Sex/Gender, Customized (Count of Participants)
    Female
    19
    76%
    21
    84%
    40
    80%
    Male
    6
    24%
    3
    12%
    9
    18%
    Other
    0
    0%
    1
    4%
    1
    2%
    Race/Ethnicity, Customized (Count of Participants)
    White
    19
    76%
    23
    92%
    42
    84%
    Black
    3
    12%
    1
    4%
    4
    8%
    Asian
    2
    8%
    1
    4%
    3
    6%
    Mixed
    1
    4%
    0
    0%
    1
    2%
    Region of Enrollment (Count of Participants)
    United States
    25
    100%
    25
    100%
    50
    100%
    Any Psychiatric Diagnosis (Count of Participants)
    Count of Participants [Participants]
    11
    44%
    11
    44%
    22
    44%

    Outcome Measures

    1. Primary Outcome
    Title NIMH Trichotillomania Symptom Severity Scale (NIMH-TSS)
    Description The entire study lasts 10 weeks. Every two weeks subjects will take the NIMH-TSS. The change in scores from baseline to after 10 weeks will be assessed. The scale itself assesses severity of trichotillomania symptoms. The NIMH-TSS score ranges from 0 to 20, with 0 being no symptoms and 20 being the most severe.
    Time Frame Assessed every two weeks up to 10 weeks, baseline data reported

    Outcome Measure Data

    Analysis Population Description
    Data provided for subjects that reported data
    Arm/Group Title Dronabinol Placebo
    Arm/Group Description Subjects will receive dronabinol 5mg once daily for two weeks, 5mg twice daily for the subsequent two weeks, and 5mg three times daily for the final six weeks. Dose escalations will only be done if the investigator deems necessary. Dronabinol: Dronabinol for 10 weeks (5mg per day first 2 weeks, 10mg per day second two weeks, 15mg per day last six weeks) Subjects will receive placebo for 10 weeks weeks. Placebo: Placebo for 10 weeks
    Measure Participants 13 16
    Mean (Standard Deviation) [score on a scale]
    12.38
    (3.15)
    10.63
    (3.42)
    2. Primary Outcome
    Title Skin Picking Symptom Assessment Scale (SP-SAS)
    Description The entire study lasts 10 weeks. Every two weeks subjects will take the SP-SAS. The change in scores from baseline to after 10 weeks will be assessed. The scale itself assesses severity of skin-picking symptoms. The SP-SAS score ranges from 0 to 48, with 0 being no symptoms and 48 being the most severe.
    Time Frame Assessed every two weeks up to 10 weeks, baseline reported

    Outcome Measure Data

    Analysis Population Description
    Data provided for subjects that reported data
    Arm/Group Title Dronabinol Placebo
    Arm/Group Description Subjects will receive dronabinol 5mg once daily for two weeks, 5mg twice daily for the subsequent two weeks, and 5mg three times daily for the final six weeks. Dose escalations will only be done if the investigator deems necessary. Dronabinol: Dronabinol for 10 weeks (5mg per day first 2 weeks, 10mg per day second two weeks, 15mg per day last six weeks) Subjects will receive placebo for 10 weeks weeks. Placebo: Placebo for 10 weeks
    Measure Participants 8 6
    Mean (Standard Deviation) [score on a scale]
    24.44
    (9.46)
    28.5
    (4.23)

    Adverse Events

    Time Frame Adverse event data was collected during the entire duration of the study (10 weeks). Subjects were asked about adverse events at each study visit and asked to reach out in between visits as well if needed to report adverse events.
    Adverse Event Reporting Description Definition does not differ from clinicaltrials.gov definition.
    Arm/Group Title Dronabinol Placebo
    Arm/Group Description Subjects will receive dronabinol 5mg once daily for two weeks, 5mg twice daily for the subsequent two weeks, and 5mg three times daily for the final six weeks. Dose escalations will only be done if the investigator deems necessary. Dronabinol: Dronabinol for 10 weeks (5mg per day first 2 weeks, 10mg per day second two weeks, 15mg per day last six weeks) Subjects will receive placebo for 10 weeks weeks. Placebo: Placebo for 10 weeks
    All Cause Mortality
    Dronabinol Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/25 (0%) 0/25 (0%)
    Serious Adverse Events
    Dronabinol Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/25 (0%) 0/25 (0%)
    Other (Not Including Serious) Adverse Events
    Dronabinol Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/25 (64%) 7/25 (28%)
    Gastrointestinal disorders
    Nausea/vomiting 1/25 (4%) 1 1/25 (4%) 1
    General disorders
    Light headed/dizzy 5/25 (20%) 5 1/1 (100%) 1
    High (easy laughing, elation, heightened awareness) 4/25 (16%) 4 0/25 (0%) 0
    Sedation 5/25 (20%) 5 3/25 (12%) 3
    Dry mouth 4/25 (16%) 4 2/25 (8%) 2
    Headache 0/25 (0%) 0 1/25 (4%) 1
    Sleep disturbance 1/25 (4%) 1 1/25 (4%) 1
    Psychiatric disorders
    Cognitive blunting, attentional problems 4/25 (16%) 4 2/25 (8%) 2
    Anxiety 2/25 (8%) 2 1/25 (4%) 1

    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.

    Results Point of Contact

    Name/Title Dr. Jon E. Grant
    Organization University of Chicago
    Phone 7738341325
    Email jgrant4@bsd.uchicago.edu
    Responsible Party:
    University of Chicago
    ClinicalTrials.gov Identifier:
    NCT03530800
    Other Study ID Numbers:
    • IRB18-0542
    First Posted:
    May 21, 2018
    Last Update Posted:
    Jun 2, 2022
    Last Verified:
    May 1, 2022