Trial Outcomes & Findings for Citicoline for Bipolar 1 Disorder and Cocaine Dependence (NCT NCT00619723)

NCT ID: NCT00619723

Last Updated: 2018-01-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

130 participants

Primary outcome timeframe

12 weeks

Results posted on

2018-01-24

Participant Flow

Participant milestones

Participant milestones
Measure	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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.
Overall Study STARTED	63	67
Overall Study COMPLETED	61	61
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Citicoline for Bipolar 1 Disorder and Cocaine Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Citicoline n=63 Participants 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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	Placebo n=67 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	63 Participants n=5 Participants	67 Participants n=7 Participants	130 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	41.1 years STANDARD_DEVIATION 9.1 • n=5 Participants	43.6 years STANDARD_DEVIATION 8.3 • n=7 Participants	42.4 years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	27 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	40 Participants n=7 Participants	87 Participants n=5 Participants
Region of Enrollment United States	63 participants n=5 Participants	67 participants n=7 Participants	130 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Outcome measures

Outcome measures
Measure	Citicoline n=61 Participants 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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	Placebo n=61 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.
Percentage of Participants With Presence of a Cocaine-Positive Urine Screen	59.0 percentage of participants	49.2 percentage of participants

SECONDARY outcome

Timeframe: 12 Weeks

As part of HRSD, the patient is rated by a clinician on 17 items that measure depressive symptom severity. The total score is calculated by summing the responses across all items. Lower scores (closer to 0) indicate the absence of depressive symptoms, while higher scores indicate the presence of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2 (0 = not present; 2 = severe). The scale range of scores is 0-52.

Outcome measures

Outcome measures
Measure	Citicoline n=61 Participants 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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	Placebo n=61 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.
Depressive Symptoms Measured Using the Hamilton Rating Scale for Depression (HRSD)	17.9 units on a scale Standard Deviation 5.6	18.0 units on a scale Standard Deviation 6.3

SECONDARY outcome

Timeframe: 12 weeks

The Young Mania Rating Scale (YMRS) is a clinician-rated scale that has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. The total score is calculated by summing answers to all the item on the scale, with a higher score indicative of more severe mania symptoms. The scale total score ranges from 0 (absence of manic symptoms) to 60 (severe manic symptoms).

Outcome measures

Outcome measures
Measure	Citicoline n=61 Participants 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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	Placebo n=61 Participants 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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.
Manic Symptoms Measured Using Young Mania Rating Scale (YMRS)	10.2 units on a scale Standard Deviation 5.9	10.1 units on a scale Standard Deviation 6.1

Adverse Events

Citicoline

Serious events: 5 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Citicoline n=61 participants at risk 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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	Placebo n=61 participants at risk 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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.
Musculoskeletal and connective tissue disorders Overnight hospitalization due to motor vehicle accident	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Musculoskeletal and connective tissue disorders Inpatient hospitalization due to improperly healing bones from previous accident	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Cardiac disorders Abnormal EKG indicating previous heart damage	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Reproductive system and breast disorders Rape	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Psychiatric disorders Suicidal Ideation	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Cardiac disorders Hospitalization due to subacute pulmonary embolism	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Blood and lymphatic system disorders Labs results indicating Leukopenia and Thrombocytopenia	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Musculoskeletal and connective tissue disorders Ankle injury	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Alcohol poisoning	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Musculoskeletal and connective tissue disorders Hairline fracture due to car accident	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Hospitalization due to flu-like symptoms	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Respiratory, thoracic and mediastinal disorders Hospitalization due to pneumonia	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.

Other adverse events

Other adverse events
Measure	Citicoline n=61 participants at risk 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. Citicoline: Citicoline is a psychostimulant/nootropic. It is an intermediate in the generation of phosphatidylcholine from choline. Cognitive Behavioral Therapy (CBT): 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.	Placebo n=61 participants at risk 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. Placebo: Inactive ingredient matching the active medication in appearance. Cognitive Behavioral Therapy (CBT): 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.
Respiratory, thoracic and mediastinal disorders ER visit due to bronchitis	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
General disorders Superficial cuts and bruising due to attack	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Skin and subcutaneous tissue disorders Lacerations on face due to fall	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Respiratory, thoracic and mediastinal disorders ER visit for breathing treatment	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Skin and subcutaneous tissue disorders ER visit after slicing head on razor wire	0.00% 0/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.6% 1/61 • Adverse events were collected during the study between 2008 and 2012. Each participant was enrolled for 12 weeks. Adverse events were collected for the full 12 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.

Additional Information

Dr. Sherwood Brown

Psychoneuroendocrine Research Group

Phone: 214-645-6950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place