Citicoline for Bipolar 1 Disorder and Cocaine Dependence
Paraules clau
Resum
Descripció
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.
Dates
Darrera verificació: | 12/31/2017 |
Primer enviat: | 02/06/2008 |
Inscripció estimada enviada: | 02/19/2008 |
Publicat per primera vegada: | 02/20/2008 |
Última actualització enviada: | 01/22/2018 |
Publicació de l'última actualització: | 01/23/2018 |
Data dels primers resultats enviats: | 04/02/2017 |
Data dels primers resultats de control de qualitat enviats: | 01/22/2018 |
Data dels primers resultats publicats: | 01/23/2018 |
: | 04/21/2013 |
: | 04/28/2013 |
: | 05/06/2013 |
Data d'inici de l'estudi real: | 03/31/2008 |
Data estimada de finalització primària: | 03/31/2012 |
Data estimada de finalització de l’estudi: | 03/31/2012 |
Condició o malaltia
Intervenció / tractament
Drug: Citicoline
Drug: Placebo
Behavioral: Cognitive Behavioral Therapy (CBT)
Fase
Grups de braços
Braç | Intervenció / tractament |
---|---|
Active Comparator: Citicoline 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 Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. |
Placebo Comparator: Placebo 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 Inactive ingredient matching the active medication in appearance. |
Criteris d'elegibilitat
Edats elegibles per estudiar | 18 Years Per a 18 Years |
Sexes elegibles per estudiar | All |
Accepta voluntaris saludables | Sí |
Criteris | 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. |
Resultat
Mesures de resultats primaris
1. Percentage of Participants With Presence of a Cocaine-Positive Urine Screen [12 weeks]
Mesures de resultats secundaris
1. Depressive Symptoms Measured Using the Hamilton Rating Scale for Depression (HRSD) [12 Weeks]
2. Manic Symptoms Measured Using Young Mania Rating Scale (YMRS) [12 weeks]