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

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01979133
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Substance Use Disorder	Drug: Icariin	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Proof of Concept Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.; Other Names: Epimedium, Horny Goat Weed, Yin Yang Huo

Outcome Measures

Primary Outcome Measures

1. 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: 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.

2. 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: 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.

3. 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: 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

4. Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit) [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)

5. Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit) [Baseline vs. 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.

6. Change in Days of Alcohol Use From Baseline to Week 8 (Exit) [Baseline vs. 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).

7. 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: 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-8849

Sponsors and Collaborators

• University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Edson S Brown, M.D., Ph.D., UT Southwestern Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sherwood Brown, E. Sherwood Brown, M.D., Ph.D., Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01979133
• Other Study ID Numbers: 082013-042
• First Posted: Nov 8, 2013
• Last Update Posted: Apr 19, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Disease; Substance-Related Disorders; Bipolar Disorder

Study Results

Participant Flow

Arm/Group Title	Icariin
Arm/Group Description	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.
Period Title: Overall Study
STARTED	10
COMPLETED	7
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Icariin
Arm/Group Description	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.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (7.3)
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 50%
White	4 40%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Rating Scale of Depression (HAMD) From Baseline to Week 8 (Exit)
Description	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.
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline HAMD Score	Week 8 HAMD Score
Measure Participants	9	9
Mean (Standard Deviation) [HAMD scale units]	17.5 (5.2)	9 (7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.012
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Change in Hamilton Rating Scale of Anxiety From Baseline to Week 8 (Exit)
Description	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.
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline HAMA Score	Week 8 HAMA Score
Measure Participants	9	9
Mean (Standard Deviation) [HAMA units on a scale]	15.2 (6.4)	4.6 (6.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Change in Quick Inventory of Depressive Symptomatology (QIDS) Score From Baseline to Week 8
Description	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
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline QIDS Score	Week 8 QIDS Score
Measure Participants	9	9
Mean (Standard Deviation) [QIDS units on a scale]	11.8 (5.9)	5.7 (4.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.017
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Change in Number of Standard Drinks of Alcohol Per Week Baseline vs. Week 8 (Exit)
Description	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)
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline Mean Standard Drinks Per Week	Week 8 Mean Standard Drinks Per Week
Measure Participants	9	9
Mean (Standard Deviation) [Drinks per week]	38.8 (45.9)	10.3 (8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.038
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Change in Number of Heavy Drinking Days From Baseline to Week 8 (Exit)
Description	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.
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline Heavy Drinking Days Per Week	Week 8 Heavy Drinking Days Per Week
Measure Participants	9	9
Mean (Standard Deviation) [Days Per Week]	3.2 (2.0)	1.2 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.034
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Change in Days of Alcohol Use From Baseline to Week 8 (Exit)
Description	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).
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline Days of alcohol use per week	Week 8 Days of alcohol use per week
Measure Participants	9	9
Mean (Standard Deviation) [Days Per Week]	4.1 (2.4)	3.3 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.231
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Primary Outcome

Title	Change in Young Mania Rating Scale (YMRS) From Baseline to Week 8 (Exit)
Description	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.
Time Frame	Baseline vs. Week 8 (Exit)

Outcome Measure Data

Analysis Population Description

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/Group Title	Baseline	Week 8
Arm/Group Description	Baseline YMRS Score	Week 8 YMRS Score
Measure Participants	9	9
Mean (Standard Deviation) [YMRS units on a scale]	8.8 (7.0)	3.3 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Week 8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.066
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Icariin
Arm/Group Description	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.
All Cause Mortality
	Icariin
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Icariin
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Icariin
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

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.