Trial of Citicoline Therapy in Patients With Mania or Hypomania and Cocaine Abuse/Dependence

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00223236
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this research is to determine if a citicoline supplement is associated with a reduction in cocaine use and craving in patients with bipolar disorder (a mental disorder marked by alternating periods of mania and depression) or schizoaffective disorder/bipolar type (a psychotic disturbance in which there is a mixture of schizophrenic and manic-depressive symptoms) and cocaine abuse/dependence. This research also wants to explore if citicoline supplements are associated with greater improvement in symptoms of mania and on memory and cognition (the mental faculty of perception, reasoning, and judgement) in these patients.

Condition or Disease	Intervention/Treatment	Phase
Mania; Hypomania; Cocaine Abuse; Cocaine Dependence	Drug: Citicoline; Drug: Placebo	Phase 3

Detailed Description

Forty-four outpatients meeting the inclusion and exclusion criteria were enrolled after completing an Institutional Review Board (IRB)-approved informed consent process. Baseline evaluation included a medical and psychiatric history, structured diagnostic interview using Diagnostic and Statistical Manual (DSM)-IV criteria, mood assessment with the Inventory of Depressive Symptomatology-Self Report (IDS-SR), Young Mania Rating Scale (YMRS), and cognitive assessment with the Rey Auditory Verbal Learning Test (RAVLT). Alternate but equivalent versions of the RAVLT were used to minimize practice effects with repeated administration. Cocaine use was assessed at each biweekly visit with urine drug screens. Citicoline or placebo was given beginning at one tablet (500 mg)/day with an increase to two tablets (1000 mg/day) at week 2, three tablets (1500 mg/day) at week 4, and four tablets (2000 mg/day) at week 6. Doses were decreased, if needed, due to side effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled Trial of Citicoline add-on Therapy in Patients With a History of Mania or Hypomania and Cocaine Abuse/Dependence
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Citicoline Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Drug: Citicoline; Citicoline or placebo will be given beginning at one table (500mg)/day with an increase to two tablets (1000mg)/day at week 2, three tablets (1500mg)/day at week 4 and four tablets (2000mg)/day at week 6. Patients will remain on 2000mg/day through week 12. Doses will be decreased if needed due to side effects.; Other Names: Cytidine-5'-diphosphocholine CDP-choline
Placebo Comparator: Placebo Inactive ingredient matching the active medication in appearance	Drug: Placebo; Placebo matching active medication in all other aspects.; Other Names: Identical placebo

Outcome Measures

Primary Outcome Measures

1. Cocaine Use Determined by Urine Analysis [Biweekly (visit) urine drug screens]

   Urine drug screens were administered at each visit to detect cocaine in urine. If negative according to urine analysis, it is determined as no cocaine use and if positive, cocaine use. Percentage of participants with no cocaine detected in urine at exit is an outcome measuring treatment effectiveness. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks.

Secondary Outcome Measures

1. Inventory of Depressive Symptomatology Self Report (IDS-SR). [Change in scores between baseline and exit (exit - baseline).]

   The IDS-SR is a 30 item self report used to assess the severity of depressive symptoms. The each item has a 4-likert scale, 0 to 3, with 3 representing the worst symptom. The total score of IDS-SR is calculated as a sum of each item score. The range of possible score is between 0 and 90, 0 as no symptom and 90 the worst symptom. The higher the score, the more severe the depression. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the tudy period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline).

2. Young Mania Rating Scale(YMRS). [Baseline to exit (exit score - baseline score)]

   The YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal and and 4 or 8 =most abnormal. The total possible score is 0 to 60, 0 being no symptom and 60 the worst symptom. The higher the score, the worse the mania symptoms are. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline).

3. Rey Auditory Verbal Learning Test(RAVLT) [Change in T scores between baseline and exit (exitT score - baseline T score).]

   The RAVLT consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. The total score is the total number of words recalled through the five trials. Normative RAVLT T-scores was used. the higher T score, the better memory. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in RAVLT T scores between baseline and exit (exit - baseline).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women ages 18-70 years

• History of mania or hypomania (bipolar I,II, not otherwise specified (NOS) or cyclothymic disorder or schizoaffective disorder/bipolar type)

• Early recovery for cocaine abuse/dependence (between 7 days and 12 weeks of enrollment).

• Any current mood state as indicated by structured diagnostic interview

• No psychotropic medication changes within 7 days prior to enrollment.

• English or Spanish speaking

Exclusion Criteria:

• Pregnant/nursing woman

• Current or past citicoline therapy

• Active suicidal or homicidal ideation with plan and intent

• Dementia, mental retardation or other severe cognitive impairment

• Severe or life threatening medical condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The UT Southwestern Medical Center of Dallas	Dallas	Texas	United States	75390-8849

Sponsors and Collaborators

• University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: E. Sherwood Brown, PH.D., M.D., The UT Southwestern Medical Center of Dallas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sherwood Brown, professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00223236
• Other Study ID Numbers: 03T-439
• First Posted: Sep 22, 2005
• Last Update Posted: Aug 11, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Mania; Cocaine-Related Disorders; Choline; Cytidine Diphosphate Choline

Study Results

Participant Flow

Recruitment Details	Patients were recruited from local community behavioral healthcare clinics and through advertising in local publications. The recruitment period was from 5/1/2004 to 4/12/2005.
Pre-assignment Detail	Participants were randomized to medication assignment after meeting the inclusion and exclusion criteria and completing the Institutional Review Board(IRB)-approved informed consent process.

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Inactive ingredient matching the active medication in appearance
Period Title: Overall Study
STARTED	16	18
COMPLETED	9	4
NOT COMPLETED	7	14

Baseline Characteristics

Arm/Group Title	Citicoline	Placebo	Total
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Inactive ingredient matching the active medication in appearance	Total of all reporting groups
Overall Participants	23	21	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	21 100%	44 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.1 (6.6)	40.7 (8.0)	41.4 (7.1)
Sex: Female, Male (Count of Participants)
Female	10 43.5%	11 52.4%	21 47.7%
Male	13 56.5%	10 47.6%	23 52.3%
Region of Enrollment (participants) [Number]
United States	23 100%	21 100%	44 100%
Inventory of Depressive Symptomatology (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	43.6 (10.6)	38.7 (13)	41.26 (11.9)
Young Mania Rating Scale (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	11.2 (4.9)	11.5 (7.0)	11.34 (5.89)
Rey Auditory Verbal Learning Scale (T scores) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T scores]	36.6 (10.0)	36.0 (9.0)	36.33 (9.47)
cocaine used (participants) [Number]
No cocaine used	19 82.6%	19 90.5%	38 86.4%
Cocaine used	4 17.4%	1 4.8%	5 11.4%
Unknown	0 0%	1 4.8%	1 2.3%

Outcome Measures

1. Primary Outcome

Title	Cocaine Use Determined by Urine Analysis
Description	Urine drug screens were administered at each visit to detect cocaine in urine. If negative according to urine analysis, it is determined as no cocaine use and if positive, cocaine use. Percentage of participants with no cocaine detected in urine at exit is an outcome measuring treatment effectiveness. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks.
Time Frame	Biweekly (visit) urine drug screens

Outcome Measure Data

Analysis Population Description

Number of participants are those who completed baseline assessment and at least one treatment visit followed by baseline.

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Inactive ingredient matching the active medication in appearance
Measure Participants	16	18
Number [percentage of participants no cocaine]	62.50 271.7%	50.00 238.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citicoline, Placebo
	Comments	Null hypothsis is no group association in cocaine use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.4637
	Comments
	Method	Chi-squared
	Comments	df=1 n=34

2. Secondary Outcome

Title	Inventory of Depressive Symptomatology Self Report (IDS-SR).
Description	The IDS-SR is a 30 item self report used to assess the severity of depressive symptoms. The each item has a 4-likert scale, 0 to 3, with 3 representing the worst symptom. The total score of IDS-SR is calculated as a sum of each item score. The range of possible score is between 0 and 90, 0 as no symptom and 90 the worst symptom. The higher the score, the more severe the depression. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the tudy period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline).
Time Frame	Change in scores between baseline and exit (exit - baseline).

Outcome Measure Data

Analysis Population Description

Number of participants reported are those who completed baseline assessment and at least one treatment visit.

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Inactive ingredient matching the active medication in appearance
Measure Participants	16	18
Mean (Standard Deviation) [units on scale]	-20.54 (14.56)	-11.89 (14.45)

3. Secondary Outcome

Title	Young Mania Rating Scale(YMRS).
Description	The YMRS questionnaire has 11 items with scale range 0 to 4 for 7 items and 0 to 8 for 4 items. 0=normal and and 4 or 8 =most abnormal. The total possible score is 0 to 60, 0 being no symptom and 60 the worst symptom. The higher the score, the worse the mania symptoms are. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in scores between baseline and exit (exit - baseline).
Time Frame	Baseline to exit (exit score - baseline score)

Outcome Measure Data

Analysis Population Description

Numbers of participants are those who completed baseline assessment and at least one treatment visit.

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Inactive ingredient matching the active medication in appearance
Measure Participants	16	18
Mean (Standard Deviation) [units on a scale]	-2.00 (8.03)	-2.88 (5.68)

4. Secondary Outcome

Title	Rey Auditory Verbal Learning Test(RAVLT)
Description	The RAVLT consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. The total score is the total number of words recalled through the five trials. Normative RAVLT T-scores was used. the higher T score, the better memory. Exit week is defined as the last week of treatment. It varied between 2 week an 12 weeks with an average exit week of 10 week and 7 week for the citicoline treatment and placebo groups, respectively. Allowing unequal week of treatment period in measuring outcome enables us to include most participants due to a low retention rate in the end of the study period, 12 weeks. The outcome was measured by change in RAVLT T scores between baseline and exit (exit - baseline).
Time Frame	Change in T scores between baseline and exit (exitT score - baseline T score).

Outcome Measure Data

Analysis Population Description

number of participants are calculated based on those who completed baseline and at least one treatment visit.

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.	Inactive ingredient matching the active medication in appearance
Measure Participants	16	17
Mean (Standard Deviation) [T score]	7.06 (11.79)	3.14 (7.07)

Adverse Events

Arm/Group Title	Citicoline		Placebo
Arm/Group Description	Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects.		Inactive ingredient matching the active medication in appearance
All Cause Mortality
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		2/21 (9.5%)
Psychiatric disorders
Hypomania	0/23 (0%)	0	1/21 (4.8%)	1
Skin and subcutaneous tissue disorders
Skin rash	1/23 (4.3%)	1	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/21 (0%)

Limitations/Caveats

Low retention rate in the end of study (12 weeks) leading to a potential underestimation of treatment effectiveness.

More Information

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.