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Citicoline for Bipolar 1 Disorder and Cocaine Dependence

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ClinicalTrials.gov Identifier: NCT00619723
Recruitment Status : Completed
First Posted : February 21, 2008
Results First Posted : January 24, 2018
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Sherwood Brown, University of Texas Southwestern Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Supportive Care
Conditions Bipolar Disorder
Cocaine Dependence
Interventions Drug: Citicoline
Drug: Placebo
Behavioral: Cognitive Behavioral Therapy (CBT)
Enrollment 130
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Citicoline Placebo
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 63 67
Completed 61 61
Not Completed 2 6
Arm/Group Title Citicoline Placebo Total
Hide Arm/Group Description

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.

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 of all reporting groups
Overall Number of Baseline Participants 63 67 130
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 67 participants 130 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
63
 100.0%
67
 100.0%
130
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 67 participants 130 participants
41.1  (9.1) 43.6  (8.3) 42.4  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 67 participants 130 participants
Female
16
  25.4%
27
  40.3%
43
  33.1%
Male
47
  74.6%
40
  59.7%
87
  66.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 63 participants 67 participants 130 participants
63 67 130
1.Primary Outcome
Title Percentage of Participants With Presence of a Cocaine-Positive Urine Screen
Hide Description 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.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Citicoline Placebo
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 61 61
Measure Type: Number
Unit of Measure: percentage of participants
59.0 49.2
2.Secondary Outcome
Title Depressive Symptoms Measured Using the Hamilton Rating Scale for Depression (HRSD)
Hide Description 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.
Time Frame 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Citicoline Placebo
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 61 61
Mean (Standard Deviation)
Unit of Measure: units on a scale
17.9  (5.6) 18.0  (6.3)
3.Secondary Outcome
Title Manic Symptoms Measured Using Young Mania Rating Scale (YMRS)
Hide Description 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).
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Citicoline Placebo
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 61 61
Mean (Standard Deviation)
Unit of Measure: units on a scale
10.2  (5.9) 10.1  (6.1)
Time Frame 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 Event Reporting Description Adverse events were assessed by a weekly questionnaire at each appointment.
 
Arm/Group Title Citicoline Placebo
Hide Arm/Group Description

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.

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.

All-Cause Mortality
Citicoline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Citicoline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   5/61 (8.20%)   8/61 (13.11%) 
Blood and lymphatic system disorders     
Labs results indicating Leukopenia and Thrombocytopenia  [1]  0/61 (0.00%)  1/61 (1.64%) 
Cardiac disorders     
Abnormal EKG indicating previous heart damage  [2]  0/61 (0.00%)  1/61 (1.64%) 
Hospitalization due to subacute pulmonary embolism  [3]  0/61 (0.00%)  1/61 (1.64%) 
General disorders     
Alcohol poisoning  [4]  0/61 (0.00%)  1/61 (1.64%) 
Hospitalization due to flu-like symptoms  [5]  1/61 (1.64%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders     
Overnight hospitalization due to motor vehicle accident  [6]  0/61 (0.00%)  1/61 (1.64%) 
Inpatient hospitalization due to improperly healing bones from previous accident  [7]  1/61 (1.64%)  0/61 (0.00%) 
Ankle injury  [8]  0/61 (0.00%)  1/61 (1.64%) 
Hairline fracture due to car accident  [9]  1/61 (1.64%)  0/61 (0.00%) 
Psychiatric disorders     
Suicidal Ideation  [10]  0/61 (0.00%)  1/61 (1.64%) 
Suicidal Ideation  [11]  0/61 (0.00%)  1/61 (1.64%) 
Reproductive system and breast disorders     
Rape  [12]  1/61 (1.64%)  0/61 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Hospitalization due to pneumonia  [13]  1/61 (1.64%)  0/61 (0.00%) 
Indicates events were collected by systematic assessment
[1]
Subjects baseline blood lab results indicated abnormal white blood cell and platelet count. Labs were repeated and revealed similar result. Subject was withdrawn from study. Event deemed as serious, unexpected and unrelated to study medication.
[2]
Subject reported after receiving abnormal EKG on 2/18/10, that he had experienced chest pains after cocaine use in January (was not reported to study personnel at time). Blind was broken and subject sent to ER for workup.
[3]
Subject hospitalized for 4 days due to subacute pulmonary embolism and was there treated with Coumadin. Subject withdrawn from study and encouraged to follow-up with physician. Event deem serious, expected, and unrelated to study medication.
[4]
Subject reported to ER due to nausea, vomiting, faintness following drinking binge. At ER, subject deemed to have alcohol poisoning and given IV fluids and released same day. Event deemed to be serious, unexpected, and unrelated to study medication.
[5]
Subject hospitalized for 2 days due to flu-like symptoms. All tests at hospital came back negative and subject was released. Event deemed as serious, unexpected and unrelated to study medication.
[6]
Released from hospital with severe bruising only. Deemed as a serious, unexpected and non-study related adverse event.
[7]
Event deemed as serious, unexpected and non-study related.
[8]
Subject experienced an ankle injury while mowing the lawn. Subject was assessed at the ER and given pain medication. Adverse event deemed as serious, unexpected, and unrelated to study medication.
[9]
Subject reported to ER after car accident. Hospitalized overnight and diagnosed with hairline fracture in ribs. Event deemed as serious, unexpected, and not related to study medication.
[10]
Subject reported suicidal ideation during study visit. Subject was assessed by study doctor and asked to agree to hospitalization. Subject refused and ran from office. Subject was contacted next day was deemed stable but withdrawn from study.
[11]
Ideation reported during study visit. Subject assessed by study personnel and created safety plan. Subject reported later in the day that ideation worsened and voluntarily committed himself to hospital. Serious, expected, unrelated to study.
[12]
Subject informed staff that she was raped. Subject denied physical injuries and was encouraged by study doctor to follow-up with primary care physician. Deemed serious, unexpected, and non-related to study medication.
[13]
Subject hospitalized for 5 days due to flu-like symptoms. In ER, subject diagnosed with pneumonia and treated with IV fluids and medication. Event deemed as serious, unexpected and unrelated to the study.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Citicoline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/61 (1.64%)   4/61 (6.56%) 
General disorders     
Superficial cuts and bruising due to attack  [1]  0/61 (0.00%)  1/61 (1.64%) 
Respiratory, thoracic and mediastinal disorders     
ER visit due to bronchitis  [2]  1/61 (1.64%)  0/61 (0.00%) 
ER visit for breathing treatment  [3]  0/61 (0.00%)  1/61 (1.64%) 
Skin and subcutaneous tissue disorders     
Lacerations on face due to fall  [4]  0/61 (0.00%)  1/61 (1.64%) 
ER visit after slicing head on razor wire  [5]  0/61 (0.00%)  1/61 (1.64%) 
Indicates events were collected by systematic assessment
[1]
Subject reported being attacked by a man with a knife while returning home from work. Subject had two 1-inch superficial cuts on right hip and minor bruise to left upper chest. Event deemed non-serious, unexpected and non-study related.
[2]
Subject went to ER due to bronchitis and was given antibiotics and released the same day.
[3]
Subject reported visiting ER for asthma breathing treatment. Subject not admitted to hospital and left after receiving breathing treatment. Event deemed non-serious, expected, and non-study related.
[4]
Subject reported slipping on water resulting in a fall on a glass vase, which led to multiple lacerations on face. Subject received stiches at ER and medication and sent home same day. Event deemed non-serious, unexpected and not related to study.
[5]
Subject received 9 staples in ER and released same day. Event deemed as non-serious, unexpected and non-study related.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Sherwood Brown
Organization: Psychoneuroendocrine Research Group
Phone: 214-645-6950
EMail: sherwood.brown@utsouthwestern.edu
Layout table for additonal information
Responsible Party: Sherwood Brown, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00619723    
Other Study ID Numbers: 122007-039
1R01DA022460-01A2 ( U.S. NIH Grant/Contract )
First Submitted: February 7, 2008
First Posted: February 21, 2008
Results First Submitted: April 3, 2017
Results First Posted: January 24, 2018
Last Update Posted: January 24, 2018