Citicoline Treatment of Methamphetamine Dependence

Study Overview
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Brief Summary
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The purpose of the study is to determine if citicoline (a nutritional supplement) is effective in helping people reduce their dependence on methamphetamine. The investigators will use neuroimaging to look at the structure and chemical make up of the brain at the start of the study and after 8-9 weeks of treatment of citicoline or placebo.

Detailed Description
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This is a prospective, randomized, double-blind, placebo-controlled study, in which we will systematically evaluate the therapeutic effects of citicoline, which may both increase dopamine and normalize cognitive and structural deficits in the brains of methamphetamine dependent subjects. Methamphetamine dependent subjects will undergo baseline and repeat cognitive assessments after 8-9 weeks of placebo or oral citicoline as a nutritional supplement. We will also evaluate the chemical and structural changes in brain regions identified by magnetic resonance spectroscopy (MRS), diffusion tension imaging (DTI) and cortical thickness, which in turn are expected to recover after 8-9 weeks of citicoline treatment. Specific brain regions of interest include the prefrontal cortices, temporal cortex, and the caudate/putamen all of which are known to be involved in the pathophysiology of methamphetamine dependence.

Official Title
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Citicoline Treatment of Methamphetamine Dependence

Conditions
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Methamphetamine Dependence

Intervention / Treatment
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* Drug: Citicoline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Methamphetamine Dependent Subject Eligibility: Inclusion Criteria: Subjects who use methamphetamine as their preferred drug of abuse. Subjects must be between the ages of 18 and 45 years. Subjects must have recent methamphetamine use (within 6 months of screening). Subjects must have an established residence and phone. Subjects must be able to give informed consent. Exclusion Criteria: Significant current or past medical, neurological, or psychiatric co-morbidity including cardiovascular, renal, and endocrine disorder, as identified by medical history. Pregnant subjects - due to the unknown effects of MRI on a fetus. In addition, women of childbearing potential who will not practice a medically accepted method of contraception will be excluded. Female subjects who are of child-bearing potential will have to pass a urine pregnancy test before each visit. Subjects who, in the investigator's judgment, pose a current serious homicidal or suicidal risk. Subjects who will not likely be able to comply with the study protocol. Subjects who have any contraindication to an MR scan. Hypersensitivity to any of the study drugs or excipients Subjects with current DSM-IV diagnosis of a major mental illness. Major illness will be defined as Major Depression, Manic Depression, Schizophrenia, Dissociative Disorder, other psychotic illnesses, Attention-Deficit Hyperactivity Disorder, Post Traumatic Stress Disorder, Borderline Personality Disorder, Reactive Attachment Disorder, and Panic Disorder. Predominant alcohol or other substance dependence as preferred drug of abuse. Positive HIV test result. An individual having any pending legal or criminal charge or action, or who has pending or a reasonable potential for court involvement, or a person who is incarcerated or is in detention, or who is pending or having completed a competency evaluation or commitment procedure. Healthy Control Subject Eligibility: Inclusion Criteria: Subjects must be between the ages of 18 and 45 years. Subjects must be able to give informed consent. To have an established residence and phone. Exclusion Criteria: Significant medical, neurological, or psychiatric disorders Pregnant subjects - due to the unknown effects of MRI on a fetus. In addition, women of childbearing potential who will not practice a medically accepted method of contraception will be excluded. Female subjects who are of child-bearing potential will have to pass a urine pregnancy test before each visit. Subjects who have any contraindication to an MR scan. Subjects unable to comply with protocol. Positive HIV test result. Positive urine drug screen.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citicoline<br>In a double-blind randomization design, subjects with methamphetamine dependence will be treated with citicoline or placebo for 8-9 weeks. | Drug: Citicoline<br>* Subjects will be given 1g citicoline twice daily for a total of 8-9 weeks.<br>* Other names: CDP-Choline;|
| Placebo Comparator: Placebo<br>In a double-blind randomization design, subjects with methamphetamine dependence will be treated with citicoline or placebo for 8-9 weeks. | Drug: Placebo<br>* Subjects will be given 1 capsule of placebo twice daily for 8-9 weeks. They will be taking the same quantity as the citicoline group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methamphetamine Dependent Subjects Treated With Citicoline vs Placebo | Total Amount of Methamphetamine consumed by the participants after 8-9 weeks of treatment. Methamphetamine was assessed twice weekly. | 8 weeks, assessed twice weekly starting week1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testing if Citicoline Administration Will be Associated With Significant Improvements in Neuropsychological Performance. | Cognitive measurement tests will be employed. | Neuropsychological testing will occur at week 0 and week 8/9 | 
| Testing if Neuroimaging Measures Will Show Significant Improvements in Brain Chemical and Structural Parameters After 8-9 Weeks of Citicoline Treatment in Methamphetamine Dependent Subjects. | Phosphorus-31 ((31)P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and β-nucleoside triphosphate (β-NTP, primarily ATP in brain) levels. | Neuroimaging will occur at week 0 and week 8/9 | 
| Testing if Improvements in Cognitive Function as Well as Brain Chemical and Structural Parameters Will be Associated With Greater Reductions in Drug Use. | Self report drug use and mood will be evaluated at each study visit throughout the course of the study. Also, urine samples will be collected twice a week for drugs of abuse testing. | Throughout the course of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methamphetamine, Citicoline, CDP-Choline, Neuroimaging, MRI, Brain, MRS, DTI