Bipolar Disorder, Substance Use Disorder
Conditions
Brief summary
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
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.
Interventions
DRUGIcariin
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.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Rating Scale of Depression (HAMD) From Baseline to Week 8 (Exit) | Baseline vs. Week 8 (Exit) | HAMD is an observer-rated measure of depressive symptomatology: 1. 17 questions (answers for individual questions range between 0-3 and 0-4). Total score range: 0-52. No subscales for this measure. 2. 0 - no depression; 52 - very severe depression (lower score corresponds to a better outcome). 3. Total score is obtained by summing questions 1-17. |
| Change in Hamilton Rating Scale of Anxiety From Baseline to Week 8 (Exit) | Baseline vs. Week 8 (Exit) | HAMA is a 14-item observer rated measure of anxiety symptomatology: 1. 14 items in a scale, no subscales. Individual items are score 0 (no anxiety) to 4 (very severe anxiety). 2. Total scores range from 0-56. 3. Total scores represent more severe anxiety. Lower scores represent a better outcome. |
| Change in Quick Inventory of Depressive Symptomatology (QIDS) Score From Baseline to Week 8 | Baseline vs. Week 8 (Exit) | The QIDS is a 16-item self-report measure of depressive symptomatology: 1. 16 items rated on a scale from 0-3. No subscales for this instrument. 2. Total score range is 0-27, where higher score represents higher levels of depression. Lower scores associated with better outcomes. 3. 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 |
| Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit) | Baseline vs. Week 8 (Exit) | 1. 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. 2. 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. 3. 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) |
| Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit) | Baseline vs. Week 8 (Exit) | 1. Heavy drinking day is defined as 5 standard drinks per day for men, and 4 standard drinks per day for women. 2. Minimum score is 0 (no drinks); maximum score is unique to each individual participant. Lower score represents a better outcome. 3. 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). 4. See outcome measure description for standard drinks per week for standard drinks convention. |
| Change in Days of Alcohol Use From Baseline to Week 8 (Exit) | Baseline vs. Week 8 (Exit) | 1. Total score range is 0-7 (no days of alcohol use - 7 days of alcohol use). The lower score represents better outcome. 2. Participants are asked to identify days on which they used alcohol in the past week (not including the day of visit). |
| Change in Young Mania Rating Scale (YMRS) From Baseline to Week 8 (Exit) | Baseline vs. Week 8 (Exit) | The YMRS is an 11-item observer-rated measure of mania symptomatology: 1. 7 individual items are scored between 0-4. 2. 4 individual items are scored between 0-8. 3. Total score range is 0-60, with no subscales. Higher score is indicative of more manic symptoms. Lower score represents better outcomes. 4. Total score is obtained by adding items on the scale together. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Icariin 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.
Icariin: 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. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Icariin |
|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 7.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Days of Alcohol Use From Baseline to Week 8 (Exit)
1. Total score range is 0-7 (no days of alcohol use - 7 days of alcohol use). The lower score represents better outcome. 2. Participants are asked to identify days on which they used alcohol in the past week (not including the day of visit).
Time frame: Baseline vs. Week 8 (Exit)
Population: The planned enrollment was 10 participants. One participant dropped out during Baseline II visit, thus researchers were unable to assess change from baseline to week 8 in this participant. As a result, the overall number of participants included in the analysis was 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Days of Alcohol Use From Baseline to Week 8 (Exit) | 4.1 Days Per Week | Standard Deviation 2.4 |
| Week 8 | Change in Days of Alcohol Use From Baseline to Week 8 (Exit) | 3.3 Days Per Week | Standard Deviation 1 |
p-value: 0.231Wilcoxon (Mann-Whitney)
Primary
Change in Hamilton Rating Scale of Anxiety From Baseline to Week 8 (Exit)
HAMA is a 14-item observer rated measure of anxiety symptomatology: 1. 14 items in a scale, no subscales. Individual items are score 0 (no anxiety) to 4 (very severe anxiety). 2. Total scores range from 0-56. 3. Total scores represent more severe anxiety. Lower scores represent a better outcome.
Time frame: Baseline vs. Week 8 (Exit)
Population: The planned enrollment was 10 participants. One participant dropped out during Baseline II visit, thus researchers were unable to assess change from baseline to week 8 in this participant. As a results, the overall number of participants analyzed was 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Hamilton Rating Scale of Anxiety From Baseline to Week 8 (Exit) | 15.2 HAMA units on a scale | Standard Deviation 6.4 |
| Week 8 | Change in Hamilton Rating Scale of Anxiety From Baseline to Week 8 (Exit) | 4.6 HAMA units on a scale | Standard Deviation 6.3 |
p-value: 0.005Wilcoxon (Mann-Whitney)
Primary
Change in Hamilton Rating Scale of Depression (HAMD) From Baseline to Week 8 (Exit)
HAMD is an observer-rated measure of depressive symptomatology: 1. 17 questions (answers for individual questions range between 0-3 and 0-4). Total score range: 0-52. No subscales for this measure. 2. 0 - no depression; 52 - very severe depression (lower score corresponds to a better outcome). 3. Total score is obtained by summing questions 1-17.
Time frame: Baseline vs. Week 8 (Exit)
Population: The total enrollment goal was 10. One participant dropped out during the baseline II visit, thus week 8 score was not obtained for that participant and the change from baseline to week 8 could not be collected. Thus, the analysis includes 9 participants instead of proposed 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Hamilton Rating Scale of Depression (HAMD) From Baseline to Week 8 (Exit) | 17.5 HAMD scale units | Standard Deviation 5.2 |
| Week 8 | Change in Hamilton Rating Scale of Depression (HAMD) From Baseline to Week 8 (Exit) | 9 HAMD scale units | Standard Deviation 7.4 |
p-value: 0.012Wilcoxon (Mann-Whitney)
Primary
Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit)
1. Heavy drinking day is defined as 5 standard drinks per day for men, and 4 standard drinks per day for women. 2. Minimum score is 0 (no drinks); maximum score is unique to each individual participant. Lower score represents a better outcome. 3. 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). 4. See outcome measure description for standard drinks per week for standard drinks convention.
Time frame: Baseline vs. Week 8 (Exit)
Population: The planned enrollment was 10 participants. One participant dropped out during Baseline II visit, thus researchers were unable to assess change from baseline to week 8 in this participant. As a result, the overall number of participants included in the analysis was 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit) | 3.2 Days Per Week | Standard Deviation 2 |
| Week 8 | Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit) | 1.2 Days Per Week | Standard Deviation 1.2 |
p-value: 0.034Wilcoxon (Mann-Whitney)
Primary
Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit)
1. 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. 2. 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. 3. 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)
Time frame: Baseline vs. Week 8 (Exit)
Population: The planned enrollment was 10 participants. One participant dropped out during Baseline II visit, thus researchers were unable to assess change from baseline to week 8 in this participant. As a result, the overall number of participants included in the analysis was 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit) | 38.8 Drinks per week | Standard Deviation 45.9 |
| Week 8 | Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit) | 10.3 Drinks per week | Standard Deviation 8.2 |
p-value: 0.038Wilcoxon (Mann-Whitney)
Primary
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: 1. 16 items rated on a scale from 0-3. No subscales for this instrument. 2. Total score range is 0-27, where higher score represents higher levels of depression. Lower scores associated with better outcomes. 3. 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
Time frame: Baseline vs. Week 8 (Exit)
Population: The planned enrollment was 10 participants. One participant dropped out during Baseline II visit, thus researchers were unable to assess change from baseline to week 8 in this participant. As a result, the overall number of participants included in the analysis was 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Quick Inventory of Depressive Symptomatology (QIDS) Score From Baseline to Week 8 | 11.8 QIDS units on a scale | Standard Deviation 5.9 |
| Week 8 | Change in Quick Inventory of Depressive Symptomatology (QIDS) Score From Baseline to Week 8 | 5.7 QIDS units on a scale | Standard Deviation 4.5 |
p-value: 0.017Wilcoxon (Mann-Whitney)
Primary
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: 1. 7 individual items are scored between 0-4. 2. 4 individual items are scored between 0-8. 3. Total score range is 0-60, with no subscales. Higher score is indicative of more manic symptoms. Lower score represents better outcomes. 4. Total score is obtained by adding items on the scale together.
Time frame: Baseline vs. Week 8 (Exit)
Population: The planned enrollment was 10 participants. One participant dropped out during Baseline II visit, thus researchers were unable to assess change from baseline to week 8 in this participant. As a result, the overall number of participants included in the analysis was 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Young Mania Rating Scale (YMRS) From Baseline to Week 8 (Exit) | 8.8 YMRS units on a scale | Standard Deviation 7 |
| Week 8 | Change in Young Mania Rating Scale (YMRS) From Baseline to Week 8 (Exit) | 3.3 YMRS units on a scale | Standard Deviation 3.5 |
p-value: 0.066Wilcoxon (Mann-Whitney)