Citicoline for Bipolar 1 Disorder and Cocaine Dependence
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric, Pulmonary, Bipolar Disorder |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 1/26/2018 |
| Start Date: | April 2008 |
| End Date: | April 2012 |
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.
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.
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.
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.
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.
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.
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