Bipolar Disorder, Cannabis-Related Disorder
Conditions
Keywords
Bipolar mania, Cannabis consumption
Brief summary
The objectives of this study are to determine whether this treatment may be useful for reducing cannabis consumption; reducing symptoms of bipolar mania; and weight mitigation therapy for individuals on psychopharmacotherapy.
Detailed description
The purpose of this research study is to study the effects (both good and bad) of combining medicines, called quetiapine and topiramate, for treating your symptoms, and other children and adolescents' symptoms, of bipolar mania (an illness with periods of elation, excessive excitement, irritability, high energy, racing thoughts, poor sleep, poor judgment, reckless behavior). It is estimated that 1% of the population of adolescents in the United States has bipolar disorder. The purpose of this research study is also to study the effects (both good and bad) of combining the same two medicines, quetiapine and topiramate, for reducing your use, and other children and adolescents' use, of cannabis (commonly referred to as pot). It is estimated that 30.5% of adolescents in the United States have used cannabis at least once in their lifetime. Additionally, the purpose of this research is to look at how bipolar disorder and cannabis use effects brain chemicals and function. Quetiapine (marketed under the brand name Seroquel) has been approved by the FDA since 1997 to help adults who suffer from schizophrenia (an illness of feeling, thought, perception and behavior). On January 12, 2004, the FDA approved quetiapine for the treatment of bipolar symptoms in adults. As of December 2009, Quetiapine has now been approved by the FDA for use in adolescents (13-17 years of age) for the treatment of schizophrenia and for the treatment of manic episodes associated with bipolar I disorder in children and adolescents (10-17 years of age). Bipolar disorder is an illness characterized by recurrent mood swings including mania (i.e., periods of elation, excessive excitement, irritability, high energy, racing thoughts, poor sleep, poor judgment, reckless behavior) and clinical depression (i.e., a depressed mood, loss of interest in activities and disruption of sleep, appetite and energy). This study is being carried out to see if quetiapine is effective and safe for treatment of children and adolescents who have the symptoms of bipolar mania. This study is also being carried out to see if quetiapine, in combination with topiramate, will further reduce bipolar mania and reduce cannabis use. As of December 2, 2009, the US Food and Drug Administration (FDA) approved SEROQUEL (quetiapine fumarate) tablets for the treatment of schizophrenia in adolescents (13-17 years of age) as monotherapy, and for the acute treatment of manic episodes associated with bipolar I disorder in children and adolescents (10-17 years of age), both as monotherapy and as an adjunct to lithium or divalproex. Topiramate (marketed under the brand name Topamax) is approved by the U.S. FDA for the prevention of migraine headaches in adults. The FDA has also approved topiramate for epilepsy (a seizure disorder) and for use as adjunctive therapy (meaning in combination with other medicines) for partial onset seizures in adults. Topiramate is not approved by the FDA for use in adults or for use in children and adolescents who have bipolar disorder. This study is being done to see if topiramate, in combination with quetiapine, will reduce bipolar mania and reduce cannabis use. The FDA has declared research studies with MRI field strengths up to and including 8 Tesla (a measure of field strength) as non-significant risk. This research study uses an MRI with a field strength of 4 Tesla.
Interventions
topiramate (titrated to 150-300 mg/day) in combination with Quetiapine (titrated to 400-800 mg/day).
placebo (titrated to 150-300 mg/day) in combination with quetiapine (titrated to 400-800 mg/day).
Sponsors
National Institute on Drug Abuse (NIDA)
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
Inclusion/
Exclusion criteria
Inclusion Criteria: To be included, all subjects must… * have an authorized parent/legal guardian who understands the nature of the study and who provides written informed consent if the study subject is younger than 18 years of age. Additionally, each subject must provide assent to the study; * be fluent in English; * be 12 to 21 years of age, inclusive; * be using a medically accepted means of contraception (i.e., oral contraceptives and barrier methods (diaphragm or condom), medroxyprogesterone acetate injectable suspension, abstinence) if female and of menarche. Oral contraceptives alone are not acceptable means of contraception because concomitant use of topiramate and low estrogen oral contraceptive pills may lead to oral contraceptive failure; * have a diagnosis of bipolar I disorder in a current manic or mixed episode, in addition to a cannabis use disorder (which includes abuse or dependence) within 28 days prior to screening, as determined by the WASH-U-KSADS; * have an initial YMRS total score of \>16 at screening and baselines; * use cannabis a minimum of twice per week on average during the 28 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Joints Per Week | 16 weeks | Change in timeline follow-back self-reported of joint equivalents per week from baseline to 16 weeks. |
| Change in Percent Days of Cannabis Use Per Week | 16 weeks | Change in percent days of cannabis use per week from baseline to week 16. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Quitiapine + Placebo Quetiapine + Placebo
quetiapine + placebo: placebo (titrated to 150-300 mg/day) in combination with quetiapine (titrated to 400-800 mg/day). | 37 |
| Quetiapine + Topiramate Quetiapine + Topiramate
Quetiapine + Topiramate: topiramate (titrated to 150-300 mg/day) in combination with Quetiapine (titrated to 400-800 mg/day). | 38 |
| Total | 75 |
Baseline characteristics
| Characteristic | Quetiapine + Topiramate | Quitiapine + Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 38 Participants | 37 Participants | 75 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 17.7 years STANDARD_DEVIATION 2.1 | 17.1 years STANDARD_DEVIATION 2.1 | 17.4 years STANDARD_DEVIATION 0.2 |
| Region of Enrollment United States | 38 participants | 37 participants | 75 participants |
| Sex: Female, Male Female | 20 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Male | 18 Participants | 19 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 37 | 23 / 38 |
| serious Total, serious adverse events | 6 / 37 | 5 / 38 |
Outcome results
Primary
Change in Joints Per Week
Change in timeline follow-back self-reported of joint equivalents per week from baseline to 16 weeks.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quitiapine and Placebo | Change in Joints Per Week | -10.1 joints | Standard Deviation 27.2 |
| Quetiapine and Topiramate | Change in Joints Per Week | -10.7 joints | Standard Deviation 18.4 |
Primary
Change in Percent Days of Cannabis Use Per Week
Change in percent days of cannabis use per week from baseline to week 16.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quitiapine and Placebo | Change in Percent Days of Cannabis Use Per Week | -29.9 cannabis use | Standard Deviation 41.1 |
| Quetiapine and Topiramate | Change in Percent Days of Cannabis Use Per Week | -43.5 cannabis use | Standard Deviation 38.1 |