CDP-Choline and Working Memory After TBI: A Neuroimaging Study

• Sponsor: Patricia M. Arenth (Other)
• Overall Status: Completed
• CT.gov ID: NCT00727246
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 19
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether an investigational drug, called "CDP-Choline", improves memory in people with traumatic brain injury (TBI). To do this, we are asking for people with traumatic brain injury and people without traumatic brain injury to be a part of this study. We will compare results between each group to see if this investigational drug makes a difference with memory. We will also compare brain imaging results and information collected before and after the taking of the study medication to see if there are any differences. We hypothesize that there will be differences in brain activation patterns between individuals with TBI and healthy controls, as well as differences in performance on memory testing at baseline. We further hypothesize that, after treatment with CDP-Choline, the patterns in neuroimaging findings and cognitive testing results for individuals with TBI will more closely resemble results observed for healthy individuals. We hope that what we learn from this study will be helpful in the future treatment of individuals with head injury.

Condition or Disease	Intervention/Treatment	Phase
Brain Injuries	Drug: CDP-Choline; Drug: Placebo	Phase 2

Detailed Description

Despite the prevalence of working memory deficits following traumatic brain injury (TBI), the scientific data regarding pharmacological treatment of this problem is limited. As deficits in working memory are known to have a significant impact on functional outcomes for individuals with TBI, further research in this area is essential in order for physicians to be able to treat this problem more effectively. The primary goal of the proposed project is to examine the efficacy of a particular pharmacological agent, CDP-Choline, in the treatment of working memory deficits following traumatic brain injury (TBI). The study sample will consist of 48 subjects: A group of 24 individuals who have sustained moderate to severe TBI, and a group of 24 healthy controls. Each group will be divided into a placebo and treatment group. The project will utilize functional Magnetic Resonance Imaging (fMRI) to investigate the cerebral neurophysiological effects of treatment with CDP-Choline. A working memory task (N-Back) will be employed during fMRI sessions. In addition, the effects of treatment with CDP-Choline on neuropsychological testing performance will also be evaluated, and the correlations between behavioral performance and neuroimaging results will be observed. We will achieve these goals by comparing baseline neuropsychological testing results as well as fMRI results, with a second set of testing and neuroimaging results obtained following 1 month of pharmacological treatment with CDP Choline or placebo. Based on our preliminary studies and the available literature, we expect to see the following: Baseline fMRI results are expected to show that individuals with TBI display altered patterns of cerebral activation during a working memory task, as compared to healthy controls. With CDP-Choline treatment, we expect TBI subjects to display fMRI laterality and dispersion patterns that more closely resemble patterns of healthy controls. In addition, we anticipate improvements in behavioral performance on both the specific working memory task (N-Back), and on traditional neuropsychological tests to be associated with CDP-Choline treatment, with greater magnitude of change on testing results for the TBI group as compared to any changes noted for the control or placebo groups. Finally, we anticipate that specific significant correlations will be observed between neuropsychological testing results and neuroimaging findings, and that the strength of these relationships will be greater for the TBI treatment group, as compared to the placebo or healthy control groups. By conducting the proposed study in this manner, we hope to provide scientific data that will allow for improved treatment, and ultimately improved functional outcomes for individuals who have sustained TBI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: CDP-Choline and Working Memory After TBI: A Neuroimaging Study.
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CDP-Choline Treatment with CDP-Choline	Drug: CDP-Choline; 1000 mg CDP-Choline 2 x per day for 6 weeks.; Other Names: Citicoline Cytidine 5'-diphosphocholine
Placebo Comparator: Placebo Treatment with Placebo	Drug: Placebo; Treatment with placebo for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Cognitive Composite Score for Group of Subjects With TBI and Healthy Controls Matched by Age, Education, and Treatment Group. [6 weeks]

   .A mean index score created as a composite cognitive performance across domains. Purpose was to serve as a measure of overall cognitive functioning for data analysis. A higher T-score indicates a higher level of cognitive function. Due to matching criteria of age range, gender and education level, as well as the small number of subjects with TBI who complete the study (n = 5), matched groups required a reduction to 2 subjects per group for analysis as planned per protocol. Due to the small number of subjects in this study overall, although analyses were run, results should be considered with caution.

2. Cognitive Composite Score for Group of Subjects With TBI and Unmatched Healthy Controls [6 weeks]

   A mean index score created as a composite cognitive performance across domains. Purpose was to serve as a measure of overall cognitive functioning for data analysis. Higher T-scores indicate higher levels of cognitive functioning. Due to the small number of subjects in this study, this second analysis was completed using the same number of subjects in the TBI and control groups, but without matching so that a slightly larger number of subject's data could be utilized. Although analyses were run, due to the very small number of participants in this study, results should be considered with caution.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

For individuals with TBI and Health Controls:

• right hand dominant

• English speaking

• No history of neurological illness (for example, stroke, seizure or brain tumor.

• No significant history of psychiatric illness (for example, schizophrenia or bipolar disorder) or current severe emotional distress.

• No visual difficulties that would not allow for reading and following written instructions.

• Free of alcohol or substance abuse.

• Capable of following basic written and oral instructions.

• Not taking certain medications that may interact with study medication or interfere with neuroimaging.

• Be able to take medication in tablet form, or crushed and dissolved in a liquid.

• Meet the additional criteria associated with MRI safety standards, as required by the University of Pittsburgh Department of Radiology. For example, these criteria include exclusion due to surgical placement of metal plates or electronic implants.

In addition:

Individuals with TBI must:

• Have a specific diagnosis of a moderate to severe traumatic brain injury, which can be confirmed through review of medical records or assessments.

• Be at least 1 year, but no more than 3 years since injury.

• Must have significant working memory problems, as indicated by performance on a screening test.

Normal Control subjects must:

• Perform within the normal range on a test of working memory.

Exclusion Criteria:

• Prisoners.

• Males with sexual partners who are planning to become pregnant during the treatment period.

• Females who are currently pregnant or who are planning to become pregnant during the treatment period.

• Individuals who are currently enrolled in another medication study

• Individuals who are currently, or have previously been, treated with CDP-Choline (Citicoline) for research or clinical purposes.

• Currently in a nursing home in the state of Pennsylvania.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh, Department of Physical Medicine & Rehabilitation	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Patricia M. Arenth
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Patricia M. Arenth, Ph.D., University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Pittsburgh School of Medicine, Department of Physical Medicine & Rehabilitation

Publications

None provided.

• Responsible Party: Patricia M. Arenth, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00727246
• Other Study ID Numbers: PRO07020121; K23HD049626
• First Posted: Aug 1, 2008
• Last Update Posted: Jul 28, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Patricia M. Arenth, Assistant Professor, University of Pittsburgh: Traumatic Brain Injury; FMRI; Memory; Cognition; Neuropsychology
• Additional relevant MeSH terms: Brain Injuries; Choline; Cytidine Diphosphate Choline

Study Results

Participant Flow

Arm/Group Title	Participants With TBI Who Received CDP-Choline	Participants With TBI Who Received Placebo	Control Participants Who Received CDP-Choline	Control Participants Who Received Placebo
Arm/Group Description	Participants who have experienced a TBI and were randomly assigned to receive the study supplement	Participants with a history of TBI who were randomly assigned to the placebo group	Individuals without a history of TBI who acted as control participants and were randomly assigned to receive CDP-Choline	Individuals without a history of TBI who participated as control subjects and were randomly assigned to receive placebo
Period Title: Overall Study
STARTED	3	3	8	5
COMPLETED	3	2	7	3
NOT COMPLETED	0	1	1	2

Baseline Characteristics

Arm/Group Title	Participants With TBI Who Received CDP-Choline	Participants With TBI Who Received Placebo	Control Participants Who Received CDP-Choline	Control Participants Who Received Placebo	Total
Arm/Group Description	Participants with TBI who were randomized to receive the CDP-Choline	Participants with TBI who were randomized to receive Placebo	Participants without a history of TBI who were randomized to receive CDP-Choline	Participants without a history of TBI who were randomized to receive placebo	Total of all reporting groups
Overall Participants	3	2	7	3	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.66 (12.42)	25 (1.41)	29 (7.90)	34 (13)	29.8 (8.98)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 50%	3 42.9%	2 66.7%	7 46.7%
Male	2 66.7%	1 50%	4 57.1%	1 33.3%	8 53.3%
Region of Enrollment (participants) [Number]
United States	3 100%	2 100%	7 100%	3 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Cognitive Composite Score for Group of Subjects With TBI and Healthy Controls Matched by Age, Education, and Treatment Group.
Description	.A mean index score created as a composite cognitive performance across domains. Purpose was to serve as a measure of overall cognitive functioning for data analysis. A higher T-score indicates a higher level of cognitive function. Due to matching criteria of age range, gender and education level, as well as the small number of subjects with TBI who complete the study (n = 5), matched groups required a reduction to 2 subjects per group for analysis as planned per protocol. Due to the small number of subjects in this study overall, although analyses were run, results should be considered with caution.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

A repeated measure ANOVA was completed to evaluate potential differences in cognitive composite scores of subjects with TBI as compared to healthy controls 6 weeks after treatment with CDP Choline (1000 mg CDP-Choline 2 x per day for 6 weeks) as compared to those treated with placebo. Matching criteria and small n for TBI group reduced group sizes.

Arm/Group Title	Participants With TBI Who Received CDP-Choline	Participants With TBI Who Received Placebo	Control Participants Who Received CDP-Choline	Control Participants Who Received Placebo
Arm/Group Description	Participants with TBI who were randomized to receive the CDP-Choline	Participants with TBI who were randomized to receive Placebo	Participants without a history of TBI who were randomized to receive CDP-Choline	Participants without a history of TBI who were randomized to receive placebo
Measure Participants	2	2	2	2
Mean (95% Confidence Interval) [T-score]	42.750	50.500	49.500	55.000

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With TBI Who Received CDP-Choline, Participants With TBI Who Received Placebo, Control Participants Who Received CDP-Choline, Control Participants Who Received Placebo
	Comments	A repeated measures ANOVA was completed to evaluate differences in cognitive composite scores of individuals with a history of TBI as compared to healthy controls 6 weeks after treatment with CDP Choline (1000 mg CDP-Choline 2 x per day for 6 weeks) as compared to those treated with placebo. A mean index score created as a composite cognitive performance across domains (higher t-score = higher cognition). Purpose was to serve as a measure of overall cognitive functioning for data analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.85
	Comments
	Method	ANOVA
	Comments	A repeated measures ANOVA was completed to evaluate differences in cognitive composite scores between groups and CDP-Choline or placebo

2. Primary Outcome

Title	Cognitive Composite Score for Group of Subjects With TBI and Unmatched Healthy Controls
Description	A mean index score created as a composite cognitive performance across domains. Purpose was to serve as a measure of overall cognitive functioning for data analysis. Higher T-scores indicate higher levels of cognitive functioning. Due to the small number of subjects in this study, this second analysis was completed using the same number of subjects in the TBI and control groups, but without matching so that a slightly larger number of subject's data could be utilized. Although analyses were run, due to the very small number of participants in this study, results should be considered with caution.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

cognitive composite scores of individuals with a history of TBI as compared to healthy controls 6 weeks after treatment with CDP Choline (1000 mg CDP-Choline 2 x per day for 6 weeks) as compared to those treated with placebo. See note above related to the limited number of subjects in each group.

Arm/Group Title	Participants With TBI Who Received CDP-Choline	Participants With TBI Who Received Placebo	Control Participants Who Received CDP-Choline	Control Participants Who Received Placebo
Arm/Group Description	Participants with TBI who were randomized to receive the CDP-Choline	Participants with TBI who were randomized to receive Placebo	Participants without a history of TBI who were randomized to receive CDP-Choline	Participants without a history of TBI who were randomized to receive placebo
Measure Participants	2	3	3	2
Mean (95% Confidence Interval) [T-score]	55.750	50.167	53.000	55.000

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With TBI Who Received CDP-Choline, Participants With TBI Who Received Placebo, Control Participants Who Received CDP-Choline, Control Participants Who Received Placebo
	Comments	A repeated measure ANOVA was completed to evaluate potential differences in cognitive composite scores of individuals with a history of TBI as compared to healthy controls 6 weeks after treatment with CDP Choline (1000 mg CDP-Choline 2 x per day for 6 weeks) as compared to those treated with placebo.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.329
	Comments
	Method	ANOVA
	Comments	A repeated measures ANOVA was completed to evaluate differences in cognitive composite scores between groups and CDP-Choline or placebo

Adverse Events

Arm/Group Title	Participants With TBI Who Received CDP-Choline		Participants With TBI Who Received Placebo		Control Participants Who Received CDP-Choline		Control Participants Who Received Placebo
Arm/Group Description	Participants who have experienced a TBI and were randomly assigned to receive the study supplement		Participants with a history of TBI who were randomly assigned to the placebo group		Individuals without a history of TBI who acted as control participants and were randomly assigned to receive CDP-Choline		Individuals without a history of TBI who participated as control subjects and were randomly assigned to receive placebo
All Cause Mortality
	Participants With TBI Who Received CDP-Choline		Participants With TBI Who Received Placebo		Control Participants Who Received CDP-Choline		Control Participants Who Received Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Participants With TBI Who Received CDP-Choline		Participants With TBI Who Received Placebo		Control Participants Who Received CDP-Choline		Control Participants Who Received Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)		0/7 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Participants With TBI Who Received CDP-Choline		Participants With TBI Who Received Placebo		Control Participants Who Received CDP-Choline		Control Participants Who Received Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/2 (0%)		2/7 (28.6%)		0/3 (0%)
Nervous system disorders
Migraine	0/3 (0%)	0	0/2 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0
Headaches (daily)	0/3 (0%)	0	0/2 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0
Social circumstances
Car Accident	1/3 (33.3%)	1	0/2 (0%)	0	0/7 (0%)	0	0/3 (0%)	0

Limitations/Caveats

Due to multiple complex issues, recruitment was significantly lower than anticipated. As a result, statistical analyses are presented, however the number of subjects in each comparison group was very low and results should be considered with caution

More Information

Certain Agreements

All Principal Investigators ARE 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.