Clinical trial NCT00619723
Conditions: Bipolar Disorder Cocaine Dependence
Sponsor: University of Texas Southwestern Medical Center
Start date: 2008-04-01; Completion date: 2012-04-01
Enrollment: 130 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A 12-week, randomized, double-blind, parallel-group, placebo-controlled trial of citicoline as an add-on therapy will be conducted in 200 outpatients with bipolar I disorder and cocaine dependence. Patients will complete mood and memory assessments weekly, in addition to completing self-report measures for cocaine (and other substances, like alcohol) use and craving. Participants will receive manual-driven Cognitive Behavioral Therapy (CBT: two sessions each week for 4 weeks followed by weekly sessions, total 16 sessions) specifically designed for persons with bipolar 1 disorder and substance abuse, and provided by a therapist with experience in CBT. The sessions may be videotaped for training purposes and may be viewed by the researchers, the therapist, and Dr. Schmitz, a clinical researcher at the University of Texas Houston who is the developer of the CBT for bipolar disorder and substance dependence used in the study. Before being videotaped, the patient will sign an "Authorization for Audio Recordings, Photography, or Other Images for Non-Treatment Purposes" to further understand how the videotape will be used, and by whom. The patient will be given the option to review their videotape to view their therapy session. Once the patient has completed all study procedures, or had discontinued the study, the tape will be destroyed, until then the tape will kept in the patient's confidential study file. Further, patients will return to the clinic three times a week for urine drug tests (UDS). 200 patients are expected to be consented for this study and all study procedures will take place at the clinic on the University of Texas Southwestern Medical Center campus.

All non-study medications are not part of the study. Non-study medication will be verbally self-reported by the patient at the time of enrollment into the study. The patient will be responsible for the costs of their non-study related medications. The patient will manage their non-study medications with their personal doctor, including any changes in these medications. However the protocol has concomitant medication algorithm in the event that a change in the medication schedule needs to be made by a study doctor. If a study doctor requests a laboratory test for the patient, it will be paid for by the clinic. Otherwise, the patient will be responsible for all costs (including laboratories) associated with their non-study medications.

Detailed description:
There will be 13 study visits where patients complete assessments, urine drug screen, and cognitive behavioral therapy (CBT). Patients will need to come to the clinic two more times in the same week to complete additional urine drug screens, for a total of 26 visits dedicated to drug screens. In the first four weeks of the study, the patients will need complete cognitive behavioral therapy twice a week, so they will need to return to the clinic for an additional visit during their first month of participation in the study. These additional visits for CBT can be combined with the urine drug screen visits, for a maximum of 39 study visits to be completed.

At the first study visit (baseline), informed consent will be obtained including a review of inclusion and exclusion criteria. A Structured Clinical Interview (SCID) Clinician Version will be performed by a research assistant to establish the diagnoses of bipolar I disorder and cocaine dependence and establish concurrent comorbid illnesses. In addition, a psychiatrist with extensive experience working with patients with bipolar 1 disorder and substance abuse will confirm diagnoses based on a clinical evaluation.

During the baseline visit, eligible participants will then be given the Inventory of Depressive Symptomatology-Self Report 30-item version (IDS-SR30), Hamilton Rating Scale for Depression 17-item version (HRSD17), Young Mania Rating Scale (YMRS), Cocaine Craving Questionnaire 45-item weekly version (CCQ), Addiction Severity Index (ASI), Psychobiology of Recovery in Depression III Somatic Symptom Scale (PRD-III), a neurocognitive battery, and a urine drug screen (UDS). The battery of neurocognitive assessments will be repeated at weeks 3, 6, and 12 (exit).

During the same visit, cocaine use in the past week (dollar amount spent/week and days used/week) will be assessed by patient self-report. Use of and craving for other substances (benzodiazepines, barbiturates, alcohol, opiates, phencyclidine, and cannabis) will also be assessed by self-report of dollar amount and days used in the past week, UDSs, and with 100-mm single item visual analog craving scales. Craving for other substances will be measured using the Clinical Institute Withdrawal Assessment of Alcohol Use-Revised (CIWA-AR), Clinical Opiate Withdrawal Scale (COWs) and Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ).

Medical and psychiatric histories will also be obtained at the baseline visit. Blood will be drawn for routine laboratory analyses including a complete blood count (CBC) and Sequential Multiple Analysis (SMA-20) at baseline and exit. The SMA-20 is a chemical test performed on serum (the portion of blood without cells). These tests include total cholesterol, total protein, various electrolytes (including sodium, potassium, chlorine), and chemicals that help the liver and kidney breakdown various substances. Both times we will draw approximately 2 tablespoons of blood, for a total of four tablespoons drawn over the course of the study.

A physical examination will be performed at baseline and exit. Women of childbearing potential will receive a urine pregnancy test and will be counseled about effective contraceptive methods. The pregnancy test will be repeated at week 4, 8, and 12 (exit) visits. The baseline visit will last approximately 3.5 hours; subsequent weekly visits will last approximately an hour.

A psychiatrist will assess the participants at baseline and weekly follow-up visits and will participate in the informed consent process. At each weekly assessment the HRSD17, IDS-SR30, YMRS, CCQ, and assessment of drug use in the past week will again be evaluated and a urine sample obtained. Adherence with study medication will be assessed through the use of the Medication Event Monitoring System (MEMS) metered dosing caps (primary measure) and pill counts.

Participants will return once each week for assessments, with additional visits for UDSs. Three UDSs will be obtained each week (Monday-Wednesday-Friday). UDS visits should last approximately 15 minutes.

The ASI will be repeated every 4 weeks. In addition, all participants will receive manual-driven CBT (two sessions each week for 4 weeks followed by weekly sessions, total 16 sessions) specifically designed for persons with bipolar 1 disorder and substance abuse, and provided by a therapist with experience in CBT. Each CBT session will last approximately one hour.

Citicoline or placebo will be given orally beginning at 500 mg/day (two tablets) with an increase to 1000 mg/day (four tablets) at week 2, 1500 mg/day (six tablets) at week 4, and 2000 mg/day (eight tablets) at week 6. Doses will be decreased if needed due to side effects.

After completing the study, patients will, if necessary, be provided standard care for bipolar 1 disorder, including continued care until symptom stabilization and referral to an outside clinic can be arranged. This post-study treatment will be provided by a blinded psychiatrist to maintain the integrity of the blind. We will make a strong effort, through phone calls and letters, to make contact with participants who withdraw from the study prior to completion to encourage them to return for a final assessment and to obtain information on the reasons for stopping treatment, perceptions of the research study and medication, and to help with arrangements for further treatment for their psychiatric illnesses outside of the study.

Arms: arm 1: Participants will receive active medication throughout the study. Citicoline will be given beginning at two capsules (500 mg/day) with an increase to four capsules (1000 mg/day) at week 2, six capsules (1500 mg/day) at week 4, and eight capsules (2000 mg/day) at week 6. Doses will be decreased, based on clinician judgment, due to side effects. arm 2: Participants will receive placebo identical in appearance to Citicoline throughout the study. Placebo will be given beginning at two capsules (500 mg/day) with an increase to four capsules (1000 mg/day) at week 2, six capsules (1500 mg/day) at week 4, and eight capsules (2000 mg/day) at week 6. Doses will be decreased, based on clinician judgment, due to side effects.
Interventions: intervention 1: Citicoline intervention 2: Placebo intervention 3: Cognitive Behavioral Therapy (CBT)
Intervention descriptions: intervention 1: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. intervention 2: Inactive ingredient matching the active medication in appearance. intervention 3: Participants will receive manual-driven Cognitive Behavioral Therapy (CBT: two sessions each week for 4 weeks followed by weekly sessions, total 16 sessions) specifically designed for persons with bipolar 1 disorder and substance abuse, and provided by a therapist with experience in CBT.

Protocol documents: