Cocaine Abuse, Cocaine Dependence, Hypomania, Mania
Conditions
Brief summary
The purpose of this research is to determine if a citicoline supplement is associated with a reduction in cocaine use and craving in patients with bipolar disorder (a mental disorder marked by alternating periods of mania and depression) or schizoaffective disorder/bipolar type (a psychotic disturbance in which there is a mixture of schizophrenic and manic-depressive symptoms) and cocaine abuse/dependence. This research also wants to explore if citicoline supplements are associated with greater improvement in symptoms of mania and on memory and cognition (the mental faculty of perception, reasoning, and judgement) in these patients.
Detailed description
Forty-four outpatients meeting the inclusion and exclusion criteria were enrolled after completing an Institutional Review Board (IRB)-approved informed consent process. Baseline evaluation included a medical and psychiatric history, structured diagnostic interview using Diagnostic and Statistical Manual (DSM)-IV criteria, mood assessment with the Inventory of Depressive Symptomatology-Self Report (IDS-SR), Young Mania Rating Scale (YMRS), and cognitive assessment with the Rey Auditory Verbal Learning Test (RAVLT). Alternate but equivalent versions of the RAVLT were used to minimize practice effects with repeated administration. Cocaine use was assessed at each biweekly visit with urine drug screens. Citicoline or placebo was given beginning at one tablet (500 mg)/day with an increase to two tablets (1000 mg/day) at week 2, three tablets (1500 mg/day) at week 4, and four tablets (2000 mg/day) at week 6. Doses were decreased, if needed, due to side effects.
Interventions
DRUGCiticoline
Citicoline or placebo will be given beginning at one table (500mg)/day with an increase to two tablets (1000mg)/day at week 2, three tablets (1500mg)/day at week 4 and four tablets (2000mg)/day at week 6. Patients will remain on 2000mg/day through week 12. Doses will be decreased if needed due to side effects.
DRUGPlacebo
Placebo matching active medication in all other aspects.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men and women ages 18-70 years * History of mania or hypomania (bipolar I,II, not otherwise specified (NOS) or cyclothymic disorder or schizoaffective disorder/bipolar type) * Early recovery for cocaine abuse/dependence (between 7 days and 12 weeks of enrollment). * Any current mood state as indicated by structured diagnostic interview * No psychotropic medication changes within 7 days prior to enrollment. * English or Spanish speaking
Exclusion criteria
* Pregnant/nursing woman * Current or past citicoline therapy * Active suicidal or homicidal ideation with plan and intent * Dementia, mental retardation or other severe cognitive impairment * Severe or life threatening medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Use Determined by Urine Analysis | Biweekly (visit) urine drug screens | Urine drug screens were administered at each visit to detect cocaine in urine. If negative according to urine analysis, it is determined as no cocaine use and if positive, cocaine use. Percentage of participants with no cocaine detected in urine at exit is an outcome measuring treatment effectiveness. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inventory of Depressive Symptomatology Self Report (IDS-SR). | Change in scores between baseline and exit (exit - baseline). | The IDS-SR is a 30 item self report used to assess the severity of depressive symptoms. The each item has a 4-likert scale, 0 to 3, with 3 representing the worst symptom. The total score of IDS-SR is calculated as a sum of each item score. The range of possible score is between 0 and 90, 0 as no symptom and 90 the worst symptom. The higher the score, the more severe the depression. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the tudy period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline). |
| Young Mania Rating Scale(YMRS). | Baseline to exit (exit score - baseline score) | The YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal and and 4 or 8 =most abnormal. The total possible score is 0 to 60, 0 being no symptom and 60 the worst symptom. The higher the score, the worse the mania symptoms are. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline). |
| Rey Auditory Verbal Learning Test(RAVLT) | Change in T scores between baseline and exit (exitT score - baseline T score). | The RAVLT consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. The total score is the total number of words recalled through the five trials. Normative RAVLT T-scores was used. the higher T score, the better memory. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in RAVLT T scores between baseline and exit (exit - baseline). |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from local community behavioral healthcare clinics and through advertising in local publications. The recruitment period was from 5/1/2004 to 4/12/2005.
Pre-assignment details
Participants were randomized to medication assignment after meeting the inclusion and exclusion criteria and completing the Institutional Review Board(IRB)-approved informed consent process.
Participants by arm
| Arm | Count |
|---|---|
| Citicoline Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects. | 23 |
| Placebo Inactive ingredient matching the active medication in appearance | 21 |
| Total | 44 |
Baseline characteristics
| Characteristic | Citicoline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 21 Participants | 44 Participants |
| Age, Continuous | 42.1 years STANDARD_DEVIATION 6.6 | 40.7 years STANDARD_DEVIATION 8 | 41.4 years STANDARD_DEVIATION 7.1 |
| cocaine used Cocaine used | 4 participants | 1 participants | 5 participants |
| cocaine used No cocaine used | 19 participants | 19 participants | 38 participants |
| cocaine used Unknown | 0 participants | 1 participants | 1 participants |
| Inventory of Depressive Symptomatology | 43.6 Units on a scale STANDARD_DEVIATION 10.6 | 38.7 Units on a scale STANDARD_DEVIATION 13 | 41.26 Units on a scale STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 23 participants | 21 participants | 44 participants |
| Rey Auditory Verbal Learning Scale | 36.6 T scores STANDARD_DEVIATION 10 | 36.0 T scores STANDARD_DEVIATION 9 | 36.33 T scores STANDARD_DEVIATION 9.47 |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 Participants |
| Young Mania Rating Scale | 11.2 Units on a scale STANDARD_DEVIATION 4.9 | 11.5 Units on a scale STANDARD_DEVIATION 7 | 11.34 Units on a scale STANDARD_DEVIATION 5.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 0 / 21 |
| serious Total, serious adverse events | 1 / 23 | 2 / 21 |
Outcome results
Primary
Cocaine Use Determined by Urine Analysis
Urine drug screens were administered at each visit to detect cocaine in urine. If negative according to urine analysis, it is determined as no cocaine use and if positive, cocaine use. Percentage of participants with no cocaine detected in urine at exit is an outcome measuring treatment effectiveness. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks.
Time frame: Biweekly (visit) urine drug screens
Population: Number of participants are those who completed baseline assessment and at least one treatment visit followed by baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Citicoline | Cocaine Use Determined by Urine Analysis | 62.50 percentage of participants no cocaine |
| Placebo | Cocaine Use Determined by Urine Analysis | 50.00 percentage of participants no cocaine |
Comparison: Null hypothsis is no group association in cocaine use.p-value: 0.4637Chi-squared
Secondary
Inventory of Depressive Symptomatology Self Report (IDS-SR).
The IDS-SR is a 30 item self report used to assess the severity of depressive symptoms. The each item has a 4-likert scale, 0 to 3, with 3 representing the worst symptom. The total score of IDS-SR is calculated as a sum of each item score. The range of possible score is between 0 and 90, 0 as no symptom and 90 the worst symptom. The higher the score, the more severe the depression. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the tudy period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline).
Time frame: Change in scores between baseline and exit (exit - baseline).
Population: Number of participants reported are those who completed baseline assessment and at least one treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citicoline | Inventory of Depressive Symptomatology Self Report (IDS-SR). | -20.54 units on scale | Standard Deviation 14.56 |
| Placebo | Inventory of Depressive Symptomatology Self Report (IDS-SR). | -11.89 units on scale | Standard Deviation 14.45 |
Secondary
Rey Auditory Verbal Learning Test(RAVLT)
The RAVLT consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. The total score is the total number of words recalled through the five trials. Normative RAVLT T-scores was used. the higher T score, the better memory. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in RAVLT T scores between baseline and exit (exit - baseline).
Time frame: Change in T scores between baseline and exit (exitT score - baseline T score).
Population: number of participants are calculated based on those who completed baseline and at least one treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citicoline | Rey Auditory Verbal Learning Test(RAVLT) | 7.06 T score | Standard Deviation 11.79 |
| Placebo | Rey Auditory Verbal Learning Test(RAVLT) | 3.14 T score | Standard Deviation 7.07 |
Secondary
Young Mania Rating Scale(YMRS).
The YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal and and 4 or 8 =most abnormal. The total possible score is 0 to 60, 0 being no symptom and 60 the worst symptom. The higher the score, the worse the mania symptoms are. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline).
Time frame: Baseline to exit (exit score - baseline score)
Population: Numbers of participants are those who completed baseline assessment and at least one treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citicoline | Young Mania Rating Scale(YMRS). | -2.00 units on a scale | Standard Deviation 8.03 |
| Placebo | Young Mania Rating Scale(YMRS). | -2.88 units on a scale | Standard Deviation 5.68 |