Citicoline for Bipolar 1 Disorder and Cocaine Dependence

NCT00619723 | Completed Phase 4 Results

• 2 other identifiers: 122007-0391R01DA022460-01A2
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Disorder; Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Presence of a Cocaine-Positive Urine Screen

  Cocaine use frequency was measured by the presence or absence of a cocaine-positive urine screen. Drug screens were obtained thrice-weekly for 12 weeks. All participants who completed the baseline assessment and at least one additional assessment were included in the primary analysis. Missing data were imputed as cocaine positive.

  12 weeks

Secondary Outcomes (2)

• Depressive Symptoms Measured Using the Hamilton Rating Scale for Depression (HRSD)

  12 Weeks

• Manic Symptoms Measured Using Young Mania Rating Scale (YMRS)

  12 weeks

Study Arms (2)

Citicoline

ACTIVE COMPARATOR

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.

Drug: Citicoline; Behavioral: Cognitive Behavioral Therapy (CBT)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Behavioral: Cognitive Behavioral Therapy (CBT)

Interventions

Citicoline DRUG

Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline.

Also known as: Cytidine diphosphate-choline (CDP-Choline), Cytidine 5'-diphosphocholine

Citicoline

Placebo DRUG

Inactive ingredient matching the active medication in appearance.

Also known as: Sugar pill

Placebo

Cognitive Behavioral Therapy (CBT) BEHAVIORAL

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.

Citicoline; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Criteria for Inclusion of Subjects: * Outpatients with a diagnosis of bipolar I disorder on the SCID and confirmed by interview with PI or co-I. * Current diagnosis of cocaine dependence, cocaine use (by self-report) within 7 days prior to baseline, and a cocaine-positive urine at baseline * Current mood state of depressed or mixed (depression plus mania) based on SCID interview using Diagnostic and Statistical Manual (DSM-IV) criteria. * Baseline HRSD17 score \< 35 and YMRS score \< 35. * On a stable medication regimen that may include mood stabilizers, antidepressants or other psychotropic medications (e.g. lithium, divalproex/valproic acid) for at least 14 days. * Age 18-65 years old. * Men and women. * English speaking individual, who can also read English. The neurocognitive measures used in this study are not available in any other languages, and must be read by the patient. There is no ability to collect this data in another manner; therefore people unable to read English may not be enrolled for participation in this study. Criteria for Exclusion of Subjects: * Bipolar disorders other than bipolar I (e.g., bipolar II, not otherwise specified (NOS), or cyclothymic disorders) based on the SCID and confirmed through clinical assessment by PI or co-I. * Mental retardation or other severe cognitive impairment, prison or jail inmates, pregnant or nursing women, or women of childbearing age who will not use hormonal contraceptives, abstinence, or other acceptable methods of birth control during the study. * Currently experiencing psychotic features (delusions, hallucinations, disorganized thought processes). * Initiation of antidepressants, mood stabilizers, or psychotherapy within the past 14 days. * High risk for suicide, defined as any suicide attempt in the past 6 months, or current suicidal ideation with plan and intent or a score of ≥ 2 on the suicide item of the HRSD17. * Intensive outpatient treatment for substance abuse (however, Alcoholics Anonymous (AA), Narcotics Anonymous (NA) meetings, or weekly therapy/counseling for bipolar disorder or substance use for at least 28 days prior to randomization will be encouraged). * Severe or life-threatening medical condition (e.g., hepatic cirrhosis, congestive heart failure, terminal cancer), laboratory or physical examination findings consistent with serious medical illness (e.g., severe edema, atrial fibrillation, dangerously abnormal electrolytes), history of severe alcohol withdrawal in the past (e.g., delirium tremens), or current clinically significant alcohol (Clinical Institute Withdrawal Assessment for Alcohol Scale \[CIWA-AR\] score \> 8 at baseline), opiate (Clinical Opiate Withdrawal Scale \[COWS\] score \> 4 are baseline) or sedative/hypnotic/anxiolytic (Benzodiazepine Withdrawal Symptom Questionnaire \[BWSQ\] \> 2). * Drug of choice is not cocaine.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Exchange Park Center, American General Building (Bass)- PNE: FL8, STE 828

Dallas, Texas, 75235, United States

Location

Related Publications (1)

• Brown ES, Todd JP, Hu LT, Schmitz JM, Carmody TJ, Nakamura A, Sunderajan P, Rush AJ, Adinoff B, Bret ME, Holmes T, Lo A. A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder. Am J Psychiatry. 2015 Oct;172(10):1014-21. doi: 10.1176/appi.ajp.2015.14070857. Epub 2015 May 22.

  PMID: 25998279 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Cocaine-Related Disorders

Interventions

Cytidine Diphosphate Choline; Sugars; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Cytidine Diphosphate; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Carbohydrates; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Dr. Sherwood Brown
• Organization: Psychoneuroendocrine Research Group

sherwood.brown@utsouthwestern.edu

214-645-6950

Study Officials

• Sherwood Brown, MD, PhD

  UTSouthwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: E. Sherwood Brown, M.D., PhD

Study Record Dates

• First Submitted: February 7, 2008
• First Posted: February 21, 2008
• Study Start: April 1, 2008
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: January 24, 2018
• Results First Posted: January 24, 2018

Record last verified: 2018-01

Locations

US (1)