Citicoline Effects on Cortical Membrane Structure and Function

Study Overview
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Brief Summary
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The goal of this project is to determine the effects of 6-week dietary supplementation with one of two doses of citicoline (250 mg/d, 500 mg/d) or placebo on prefrontal cortical membrane dynamics (31P-MRS) and event-related functional activation (fMRI) in healthy middle-aged adults.

Detailed Description
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To determine the effect of citicoline supplementation on cortical structure and function in healthy middle-aged adults. Test 1: The effect of citicoline (500 mg/d) compared with placebo on event-related anterior cingulate cortex (ACC) activation during sustained attention by fMRI. Test 2: The effect of citicoline (500 mg/d) compared with placebo on reaction time and increasing accuracy on the sustained attention task (CPT-IP). Test 3: The effect of citicoline compared with placebo on phosphodiester (PDE) and b-NTP levels in the ACC by 31P-MRS. Test 4: ACC activation and CPT-IP performance (fMRI) and ACC PDE levels (31P-MRS) following high-dose citicoline (500 mg/d) compared with placebo at Week 3. Test 5: The effect of low-dose citicoline (250 mg/d) compared with placebo on an ACC activation and CPT-IP performance (fMRI) and ACC PDE levels (31P-MRS). Test 6: Among all subjects (n=60), the relationship between baseline red blood cell (RBC) omega-3 fatty acid (EPA+DHA) levels and ACC activation, ACC PDE levels, or the effects of citicoline.

Official Title
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Citicoline Effects on Cortical Membrane Structure and Function

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Citicoline supplement
* Dietary Supplement: Placebo supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent; Ages 40-60 years old; Right handed. If female, not pregnant (as determined by a positive pregnancy test); and agrees to use one of the following methods of birth control: abstinence from sexual intercourse, barrier (diaphragm or condom), or oral/injectable contraceptive; Exclusion Criteria: Contraindication to an MRI scan (i.e., braces, claustrophobia, pacemaker etc); A history of a major medical (e.g., diabetes) or neurological illness (e.g., epilepsy); Body mass index (BMI) ≥ 30; An IQ <75 and >130; A positive urine drug test (nicotine dependence is permitted); Personal history of a DSM-5 Axis I psychiatric disorder; Requiring treatment with a drug which might obscure the action of the study treatment.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Cellulose)<br> | Dietary Supplement: Placebo supplement<br>* Cellulose<br>* Other names: Placebo;|
| Experimental: Cognizin 250 mg/day<br> | Dietary Supplement: Citicoline supplement<br> <br> * Other names: Cognizin;|
| Experimental: Cognizin 500 mg/day<br> | Dietary Supplement: Citicoline supplement<br> <br> * Other names: Cognizin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phosphodiester (PDE) concentrations in the ACC by 31P-MRS |  | 6 weeks | 
| b-NTP concentrations in the ACC by 31P-MRS |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood oxygenation level-dependent signal in the ACC during sustained attention by fMRI |  | 6 weeks | 
| Reaction time (ms) on an attention task (CPT-IP) |  | 6 weeks | 
| Accuracy (percent correct) on an attention task (CPT-IP) |  | 6 weeks |