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

• ClinicalTrials.gov Identifier: NCT00223236
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Results First Posted: August 11, 2014
• Last Update Posted: August 11, 2014
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Sherwood Brown, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mania; Hypomania; Cocaine Abuse; Cocaine Dependence	Drug: Citicoline; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled Trial of Citicoline add-on Therapy in Patients With a History of Mania or Hypomania and Cocaine Abuse/Dependence
• Study Start Date: July 2010
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: May 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Citicoline; Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Drug: Citicoline; 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.; Other Names: Cytidine-5'-diphosphocholine; CDP-choline
Placebo Comparator: Placebo; Inactive ingredient matching the active medication in appearance	Drug: Placebo; Placebo matching active medication in all other aspects.; Other Name: Identical placebo

Outcome Measures

Primary Outcome Measures :

1. Cocaine Use Determined by Urine Analysis [ Time Frame: 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 Outcome Measures :

1. Inventory of Depressive Symptomatology Self Report (IDS-SR). [ Time Frame: 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).
2. Young Mania Rating Scale(YMRS). [ Time Frame: 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).
3. Rey Auditory Verbal Learning Test(RAVLT) [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

The UT Southwestern Medical Center of Dallas

Dallas, Texas, United States, 75390-8849

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: E. Sherwood Brown, PH.D., M.D.; The UT Southwestern Medical Center of Dallas

More Information

• Responsible Party: Sherwood Brown, professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00223236
• Other Study ID Numbers: 03T-439
• First Posted: September 22, 2005
• Results First Posted: August 11, 2014
• Last Update Posted: August 11, 2014
• Last Verified: August 2014

Additional relevant MeSH terms:

Mania; Cocaine-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Choline; Cytidine Diphosphate Choline; Lipotropic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Lipid Regulating Agents; Nootropic Agents