Methamphetamine Dependence
Conditions
Keywords
methamphetamine, Citicoline, CDP-Choline, Neuroimaging, MRI, Brain, MRS, DTI
Brief summary
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
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.
Interventions
DRUGCiticoline
Subjects will be given 1g citicoline twice daily for a total of 8-9 weeks.
DRUGPlacebo
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.
Sponsors
National Institute on Drug Abuse (NIDA)
Perry Renshaw
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Methamphetamine Dependent Subjects Treated With Citicoline vs Placebo | 8 weeks, assessed twice weekly starting week1 | Total Amount of Methamphetamine consumed by the participants after 8-9 weeks of treatment. Methamphetamine was assessed twice weekly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Testing if Citicoline Administration Will be Associated With Significant Improvements in Neuropsychological Performance. | Neuropsychological testing will occur at week 0 and week 8/9 | Cognitive measurement tests will be employed. |
| 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. | Neuroimaging will occur at week 0 and week 8/9 | 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. |
| Testing if Improvements in Cognitive Function as Well as Brain Chemical and Structural Parameters Will be Associated With Greater Reductions in Drug Use. | Throughout the course of the study | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Citicoline 74 subjects with methamphetamine dependence were treated with citicoline for 8-9 weeks.
Citicoline: Subjects were given 1g citicoline twice daily for a total of 8-9 weeks. | 72 |
| Placebo 32 subjects with methamphetamine dependence were treated with citicoline for 8-9 weeks.
Placebo: Subjects were given 1 capsule of placebo twice daily for 8-9 weeks. They will be taking the same quantity as the citicoline group. | 32 |
| Total | 104 |
Baseline characteristics
| Characteristic | Placebo | Citicoline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 72 Participants | 104 Participants |
| Age, Continuous | 31.4 years STANDARD_DEVIATION 7.1 | 32.9 years STANDARD_DEVIATION 6.8 | 32.4 years STANDARD_DEVIATION 6.89 |
| Region of Enrollment United States | 32 participants | 72 participants | 104 participants |
| Sex: Female, Male Female | 14 Participants | 33 Participants | 47 Participants |
| Sex: Female, Male Male | 18 Participants | 39 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 72 | 14 / 32 |
| serious Total, serious adverse events | 2 / 72 | 0 / 32 |
Outcome results
Primary
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.
Time frame: 8 weeks, assessed twice weekly starting week1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citicoline | Methamphetamine Dependent Subjects Treated With Citicoline vs Placebo | 0.3025 total amount consumed in grams | Standard Deviation 0.16498 |
| Placebo | Methamphetamine Dependent Subjects Treated With Citicoline vs Placebo | 0.3850 total amount consumed in grams | Standard Deviation 0.34547 |
Secondary
Testing if Citicoline Administration Will be Associated With Significant Improvements in Neuropsychological Performance.
Cognitive measurement tests will be employed.
Time frame: Neuropsychological testing will occur at week 0 and week 8/9
Secondary
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.
Time frame: Throughout the course of the study
Secondary
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.
Time frame: Neuroimaging will occur at week 0 and week 8/9