A Pilot Study of Citicoline add-on Therapy in Patients With Bipolar Disorder or Major Depressive Disorder and Amphetamine Abuse or Dependence

• ClinicalTrials.gov Identifier: NCT00377299
• Recruitment Status: Completed
• First Posted: September 18, 2006
• Results First Posted: August 8, 2013
• Last Update Posted: August 8, 2013
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: Stanley Medical Research Institute
• Information provided by (Responsible Party): 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: Treatment
• Conditions: Amphetamine Abuse; Amphetamine Dependence; Bipolar Disorder; Major Depressive Disorder
• Interventions: Drug: Citicoline; Drug: Placebo
• Enrollment: 60

Participant Flow

Recruitment Details	Sixty depressed outpatients with methamphetamine dependence were enrolled and randomized for 12 weeks of acute treatment after completing an IRB-approved written informed consent The study was conducted at the UT Southwestern Medical Center in Dallas. The first participant was enrolled on 10/11/06 and the final assessment was on 4/7/09.
Pre-assignment Details

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Citicoline add-on therapy was given beginning at one tablet(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 remained on 2000mg/day throughout the remaining weeks of the study (week 12). Doses were decreased, if needed, due to side effects.	Placebo identical in appearance to the medication was given beginning at one tablet with an increase to two tablets at week 2, three tablets at week 4 and four tablets at week 6. Patients remained on four tables throughout the remaining weeks of the study (week 12). Doses were decreased, if needed, due to side effects.
Period Title: Overall Study
Started	32	28
Completed	13	4
Not Completed	19	24
Reason Not Completed
Lost to Follow-up	14	19
Adverse Event	0	1
Withdrawal by Subject	5	4

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.	[Not Specified]	Total of all reporting groups
Overall Number of Baseline Participants		32	28	60
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	32 participants	28 participants	60 participants
		41.0 (9.6)	34.0 (7.4)	37.8 (9.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	28 participants	60 participants
	Female	17 53.1%	11 39.3%	28 46.7%
	Male	15 46.9%	17 60.7%	32 53.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	28 participants	60 participants
	American Indian or Alaska Native	0 0.0%	1 3.6%	1 1.7%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	28 87.5%	20 71.4%	48 80.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	4 12.5%	7 25.0%	11 18.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	32 participants	28 participants	60 participants
		32	28	60

Outcome Measures

1. Primary Outcome

Title	Depression Symptoms
Description	Inventory of Depressive Symptomatology-Clinician Rated (IDS-C), (a clinician-administered depression scale) is used to assess the severity of depressive symptoms.Scores can range from 0 to 84. The higher the score, the worse the depressive symptoms(worse outcome).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) group includes all who returned for at least one post baseline visit. Analysis uses Last Observation Carried Forward (LOCF) method.

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.	Placebo.
Overall Number of Participants Analyzed	28	20
Mean (Standard Error); Unit of Measure: scores on a scale
	26.2 (2.5)	33.1 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citicoline, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.05
	Comments	Significance was set at a p value of ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

2. Secondary Outcome

Title	Amphetamine Craving
Description	Visual Analog Scale (VAS) assessing Methamphetamine craving with a 1-100 scale.Higher values on the VAS scale indicate a higher Methamphetamine craving(worse outcome).
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

ITT includes those returning for at least one post baseline visit. LOCF used for end point data.

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.	Placebo.
Overall Number of Participants Analyzed	19	27
Mean (Standard Error); Unit of Measure: scores on a scale
	31.9 (8.0)	44.1 (9.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citicoline, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.05
	Comments	Significance was set at a p value of ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

3. Secondary Outcome

Title	Amphetamine Use
Description	Participant reported days per 7-day week of methamphetamine use.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT includes those returning for at least one post baseline visit. LOCF used for end point data.

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.	Placebo matching Citicoline.
Overall Number of Participants Analyzed	28	20
Mean (Standard Error); Unit of Measure: days per week
	2.9 (0.6)	2.3 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citicoline, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.05
	Comments	Significance was set at a p value of ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

4. Secondary Outcome

Title	Hopkins Auditory Verbal Learning Test (HVLT)
Description	The Hopkins Auditory Verbal Learning Test (HVLT) is a measure of cognition (memory/recall). Raw scores are derived for Total Recall, Delayed Recall, Retention (% retained), and a Recognition Discrimination Index. Raw scores are calculated into T-scores. T-scores are standardized scores on each dimension for each type. A score of 50 represents the mean. A difference of 10 from the mean indicates a difference of one standard deviation. Thus, a score of 60 is one standard deviation above the mean, while a score of 30 is two standard deviations below the mean.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT includes those returning for at least one post baseline visit. LOCF used for end point data.

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.	Placebo matching Citicoline.
Overall Number of Participants Analyzed	17	9
Mean (Standard Error); Unit of Measure: T score
	38.5 (3.8)	47.5 (4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citicoline, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.05
	Comments	Significance was set at a p value of ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

5. Secondary Outcome

Title	Stroop Color Word Test
Description	The Stroop Color Word Test measures the individual's ability to separate the word and color naming stimuli thus the ability to sort information from the environment and selectively react to this information. The scoring is a measure of time to complete 100 items and the numbers of items that can be completed. THe scores are converted into T-scores which have a mean of 50 and a standard deviation of 10.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

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.	Placebo.
Overall Number of Participants Analyzed	28	20
Mean (Standard Error); Unit of Measure: T score
	56.2 (2.6)	54.3 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Citicoline, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.05
	Comments	Significance was set at a p value of ≤ 0.05.
	Method	ANCOVA
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
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.		[Not Specified]
All-Cause Mortality
	Citicoline		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.13%)		4/28 (14.29%)
Injury, poisoning and procedural complications
Injuries Due to Car Accident † [1]	1/32 (3.13%)	1	0/28 (0.00%)	0
Drug Overdose † [2]	0/32 (0.00%)	0	1/28 (3.57%)	1
Car Accident † [1]	0/32 (0.00%)	0	1/28 (3.57%)	1
Psychiatric disorders
Drug Overdose / Suicidal Gesture † [2]	0/32 (0.00%)	0	1/28 (3.57%)	1
Psychiatric Hospitalization Involuntary † [3]	0/32 (0.00%)	0	1/28 (3.57%)	1
† Indicates events were collected by systematic assessment; [1] Participant was in a motor vehicle accident.; [2] Overdose.; [3] Psychiatric hospitalization.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/32 (6.25%)		0/28 (0.00%)
Infections and infestations
Tooth Abscess and Infection † [1]	1/32 (3.13%)	1	0/28 (0.00%)	0
Psychiatric disorders
Severe Panic Attack † [2]	1/32 (3.13%)	1	0/28 (0.00%)	0
† Indicates events were collected by systematic assessment; [1] Participant reported an abscessed/infected tooth and received amoxycillin.; [2] Participant with a history of panic attacks experienced a severe panic attack. Attack resolved without need for medical intervention.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. E. Sherwood Brown, M.D., Ph.D.
• Organization: UT Southwestern Medical Center at Dallas
• Phone: 214-645-6950
• EMail: sherwood.brown@utsouthwestern.edu

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00377299
• Other Study ID Numbers: 052006-27
• First Submitted: September 14, 2006
• First Posted: September 18, 2006
• Results First Submitted: September 8, 2011
• Results First Posted: August 8, 2013
• Last Update Posted: August 8, 2013