Treatment With Quetiapine for Youth With Substance Use Disorders and Severe Mood Dysregulation

Study Overview
=================
Brief Summary
-----------------
This study proposes to use quetiapine as an adjunct treatment to treatment as usual to improve both substance use disorder (SUD) and mood symptoms in youth with SUD and severe mood dysregulation (SMD). This is a randomized, double blind placebo controlled parallel design study. Youth with symptoms of mood dysregulation and active substance use that meets criteria for a SUD will be randomized to adjunct treatment with quetiapine or placebo. The investigators hypothesize that treatment with quetiapine will lead to a reduction in substance use, improvement in mood, and lead to greater engagement in outpatient treatment.

Official Title
-----------------
A Randomized Controlled Trial of Quetiapine for the Treatment of Youth With Co-occurring Substance Use Disorders and Severe Mood Dysregulation

Conditions
-----------------
Substance Use Disorders, Bipolar Disorder, Mood Disorders

Intervention / Treatment
-----------------
* Drug: Quetiapine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female age 15 to 24 Meet DSM-5 criteria for a substance use disorder Substance use ≥ 14 days of past 28 days (i.e. use ≥ 50% of days in the past 28 days) If subject in restricted setting/care (e.g. inpatient detox unit or residential treatment) for ≤ 2 weeks, then use ≥ 50% of days while outside of restricted setting (e.g. 7 days of substance use out of 14 days in unrestricted setting) Subjects need to have been in an unrestricted setting for at least 2 weeks prior to screening Meets DSM-5 criteria for bipolar disorder or disruptive mood dysregulation disorder or DSM IV criteria for mood disorder not otherwise specified Symptoms of SMD: Youth Self Report (YSR) or Adult Self Report (ASR) AAA ≥180 Stable to be treated in outpatient level of care Exclusion Criteria: Current methamphetamine use disorder Current unstable opioid use disorder (i.e. < 3 months on medication assisted treatment for an opioid use disorder) Pregnant or breastfeeding Placement in a restricted setting (e.g. detox or residential treatment) for ≥ 2 weeks out of past 28 days prior to screening visit, or placement in a restricted setting at anytime during study participation Unwilling or unable to use effective birth control Unwilling or unable to sign release of information for the treatment program providing behavioral treatment For participants >17 years-unable or unwilling to identify emergency contact

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 24 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine<br>Quetiapine | Drug: Quetiapine<br>* Participants will be randomly assigned Quetiapine and will be titrated to the maximum daily dose over three weeks and then enter a dose maintenance phase for weeks 4 through 8 of the study.<br>* Other names: Seroquel;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Participants will be randomly assigned to placebo and will be titrated to the maximum daily dose over three weeks and then enter a dose maintenance phase for weeks 4 through 8 of the study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Timeline Followback of Substance Use (TLFB) | The TLFB is used to quantify self-reported drug of choice use during the past month. Counts the number of days with substance use in the past 28 days. | baseline, 8 weeks | 
| Change in Symptoms of Mania | Symptoms of mania will be assessed using the Young Mania Rating Scale (YMRS). The YMRS consists of 11 items rated on a scale. Each item is composed of 5 explicitly defined levels of severity. Severity ratings for 7 items are scored on a scale of 0 -4. The remaining 4 items are double weighted to account for poor cooperation of client when unwell and are scored on a scale of 0 - 8. Item ratings are sum to produce a total YMRS score between 0 -60. Higher scores on the YMRS indicate greater symptoms of mania. | baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Number of Negative Urine Toxicology Specimens | Urine toxicology specimens for the participant's drug of choice assessed as positive or negative. For each participant, the proportion of urine toxicology specimens that are negative over the course of the trial are calculated as the number of negative specimens divided by the total number of specimens collected from week 1 until study endpoint. | baseline, 8 weeks | 
| Change in Craving for the Substance That the Participant Identifies as Most Problematic | Craving will be measured by the Weiss Craving Scale. This scale consists of 3 items rated on a scale from 0 (no desire/likelihood of use) to 9 (strong desire/likelihood of use). The total Weiss Craving Scale score ranges from 0 to 27. Higher scores on the Weiss Craving Scale indicate greater cravings for a substance. | baseline, 8 weeks | 
| Change in Symptoms of Depression | Symptoms of depression will be assessed using the Beck Depression Inventory II (BDI-II) scale. The BDI-II consists of 21 items rated on a scale from 0 (symptoms not present) to 3 (symptoms extremely severe). Total scores on the BDI-II range from 0 to 63. Higher scores indicate greater symptoms of depression. | baseline, 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
youth, adolescent, young adult, substance use disorder, bipolar disorder, quetiapine, mood dysregulation