Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders

Study Overview
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Brief Summary
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This study is being done to see if icariin will help with depression in patients with bipolar disorder and alcohol or cocaine use disorders. The pills used in this study contain 20% icariin.

Detailed Description
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Ten adults with current bipolar disorder (BPD) and current cocaine or alcohol use disorders, based on a structured clinical interview (SCID), and a baseline Hamilton Rating Scale for Depression (HAMD) score of ≥ 15, will be recruited through a patient database of a recently completed study of bipolar disorder patients with cocaine dependence. Informed consent will be obtained. The clinician version of the structured Clinical Interview for DSM-IV (SCID) is a brief structured interview for major Axis I disorders in DSM-IV including major depressive disorder, dysthymic disorder, bipolar disorders, psychotic disorders, anxiety disorders, eating disorders, and alcohol and substance abuse/dependence. This will be given at baseline to confirm bipolar disorder diagnosis. Blood draws and a physical examination by a physician will be performed at baseline to general physical health. Participants will return to receive icariin (100 mg/day)once their general health and diagnosis are confirmed. Participants will be assessed at baseline and weekly with the HAMD and a urine drug screen, for 8 consecutive weeks after initiating intervention (icariin). A dose titration from 100 mg/day to 200 mg/day will be allowed at week 3 for participants with less than a 30% reduction in HAMD and/or still using cocaine or alcohol or have a positive urine drug screen. An additional dose titration to 300 mg/day will be allowed at week 6 for participants with less than a 50% reduction in HAMD scores and/or still using cocaine or alcohol or have a positive urine drug screen. Pill counts will be conducted, and a list of current medications and doses will be obtained at each visit. Participants will be compensated and receive bus passes at each appointment. Participants will be evaluated by both the research assistant (RA) and principal investigator (PI) at each follow-up appointment. The HAM-D will be the primary outcome measure. Other cognitive assessments will be performed at these same visits as well.

Official Title
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A Proof of Concept Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders

Conditions
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Bipolar Disorder, Substance Use Disorder

Intervention / Treatment
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* Drug: Icariin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current BPD I, II or NOS and cocaine or alcohol use disorder with HAMD score of ≥ 15 Cocaine or alcohol use with 5 days of initiating study drug Men and women Age 18-70 years Exclusion Criteria: Psychotic features Non-English speakers Treatment resistant depression defined as failure of a trial of antidepressants (≥ 4 weeks at a therapeutic dose) in current episode Major medical condition including heart, lung, liver or renal disease, cancer, neurological or immunological conditions Vulnerable populations including prisoners, cognitively impaired individuals, and pregnant or nursing women Prior side effects or allergic reactions to icariin-containing preparations Change in psychotropic medications within 14 days of study entry Current suicidal ideation (plan and intent), a suicide attempt within the past 12 months or history of > 1 lifetime suicide attempt

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: icariin<br>Icariin will be given 100 mg/day. A dose titration from 100 mg/day to 200 mg/day will be allowed at week 3 for participants with less than a 30% reduction in HAMD and/or still using cocaine or alcohol or have a positive urine drug screen. An additional dose titration to 300 mg/day will be allowed at week 6 for participants with less than a 50% reduction in HAMD scores and/or still using cocaine or alcohol or have a positive urine drug screen. | Drug: Icariin<br>* Participants will receive 20% icariin (100 mg/day) in a commercially available over-the-counter Horny Goat Weed supplement. A dose titration from 100 mg/day to 200 mg/day will be allowed at week 3 participants with less than a 30% reduction in HAMD and/or still using cocaine or alcohol or have a positive urine drug screen. An additional dose titration to 300 mg/day will be allowed at week 6 for participants with less than a 50% reduction in HAMD scores and/or still using cocaine or alcohol or have a positive urine drug screen.<br>* Other names: Epimedium, Horny Goat Weed, Yin Yang Huo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Rating Scale of Depression (HAMD) From Baseline to Week 8 (Exit) | HAMD is an observer-rated measure of depressive symptomatology: 17 questions (answers for individual questions range between 0-3 and 0-4). Total score range: 0-52. No subscales for this measure. 0 - no depression; 52 - very severe depression (lower score corresponds to a better outcome). Total score is obtained by summing questions 1-17. | Baseline vs. Week 8 (Exit) | 
| Change in Hamilton Rating Scale of Anxiety From Baseline to Week 8 (Exit) | HAMA is a 14-item observer rated measure of anxiety symptomatology: 14 items in a scale, no subscales. Individual items are score 0 (no anxiety) to 4 (very severe anxiety). Total scores range from 0-56. Total scores represent more severe anxiety. Lower scores represent a better outcome. | Baseline vs. Week 8 (Exit) | 
| Change in Quick Inventory of Depressive Symptomatology (QIDS) Score From Baseline to Week 8 | The QIDS is a 16-item self-report measure of depressive symptomatology: 16 items rated on a scale from 0-3. No subscales for this instrument. Total score range is 0-27, where higher score represents higher levels of depression. Lower scores associated with better outcomes. Total score is obtained using the following formula: highest score on items 1-4 + item 5 + highest score on items 6-9 + item 10+item 11+item12+item13+item14+highest score on items 15-16 | Baseline vs. Week 8 (Exit) | 
| Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit) | Participants are asked to identify the number of alcoholic drinks they consumed on each day within the last 7 days from the day of visit (not including the day of visit). Participants are asked to provide alcohol name and the amount of alcohol they consumed. These values are then converted to standard drinks using a standard drinks calculator. The minimum number of drinks per week is 0. There is no maximum number of drinks per week, as the maximum number is unique to each participant. The general convention for standard drinks used in this study is as follows (oz per one standard drink): beer: 12 fl oz (5% ABV) wine: 5 fl oz (10-12% ABV or 18-20% ABV for fortified wine) hard liquor: 1.5 fl oz (40% ABV) | Baseline vs. Week 8 (Exit) | 
| Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit) | Heavy drinking day is defined as 5 standard drinks per day for men, and 4 standard drinks per day for women. Minimum score is 0 (no drinks); maximum score is unique to each individual participant. Lower score represents a better outcome. Average number of heavy drinking days per week is calculated by asking participants to identify the number of drinks they had on each day during the past 7 days (not including the day of visit). See outcome measure description for standard drinks per week for standard drinks convention. | Baseline vs. Week 8 (Exit) | 
| Change in Days of Alcohol Use From Baseline to Week 8 (Exit) | Total score range is 0-7 (no days of alcohol use - 7 days of alcohol use). The lower score represents better outcome. Participants are asked to identify days on which they used alcohol in the past week (not including the day of visit). | Baseline vs. Week 8 (Exit) | 
| Change in Young Mania Rating Scale (YMRS) From Baseline to Week 8 (Exit) | The YMRS is an 11-item observer-rated measure of mania symptomatology: 7 individual items are scored between 0-4. 4 individual items are scored between 0-8. Total score range is 0-60, with no subscales. Higher score is indicative of more manic symptoms. Lower score represents better outcomes. Total score is obtained by adding items on the scale together. | Baseline vs. Week 8 (Exit) |