Citicoline for Bipolar 1 Disorder and Cocaine Dependence
Condition: Bipolar Disorder; Cocaine Dependence
MeSH terms: Cocaine-Related Disorders; Bipolar Disorder
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Citicoline; Placebo; Cognitive Behavioral Therapy (CBT)
Intervention type(s): Drug; Drug; Behavioral
Intervention description(s): Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline.; Inactive ingredient matching the active medication in appearance.; 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.
Other intervention name(s): Cytidine diphosphate-choline (CDP-Choline); Cytidine 5'-diphosphocholine; Sugar pill
Intervention MeSH terms: Choline; Cytidine Diphosphate Choline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care