Trial of Citicoline Therapy in Patients With Mania or Hypomania and Cocaine Abuse/Dependence

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Double-blind, Placebo-controlled Trial of Citicoline add-on Therapy in Patients With a History of Mania or Hypomania and Cocaine Abuse/Dependence

Conditions
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Mania, Hypomania, Cocaine Abuse, Cocaine Dependence

Intervention / Treatment
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* Drug: Citicoline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Citicoline<br>Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects. | Drug: Citicoline<br>* 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.<br>* Other names: CDP-choline;|
| Placebo Comparator: Placebo<br>Inactive ingredient matching the active medication in appearance | Drug: Placebo<br>* Placebo matching active medication in all other aspects.<br>* Other names: Identical placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Biweekly (visit) urine drug screens | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Change in scores between baseline and exit (exit - baseline). | 
| 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). | Baseline to exit (exit score - baseline score) | 
| 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). | Change in T scores between baseline and exit (exitT score - baseline T score). |