Citicoline Treatment of Methamphetamine Dependence

• Sponsor: Perry Renshaw (Other)
• Overall Status: Completed
• CT.gov ID: NCT00950352
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 104
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence	Drug: Citicoline; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Citicoline Treatment of Methamphetamine Dependence
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Citicoline In a double-blind randomization design, subjects with methamphetamine dependence will be treated with citicoline or placebo for 8-9 weeks.	Drug: Citicoline; Subjects will be given 1g citicoline twice daily for a total of 8-9 weeks.; Other Names: CDP-Choline
Placebo Comparator: Placebo In a double-blind randomization design, subjects with methamphetamine dependence will be treated with citicoline or placebo for 8-9 weeks.	Drug: Placebo; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Brain Institute of the University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

• Perry Renshaw
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Perry F Renshaw, MD, PhD, MBA, University of Utah

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Brain Institute
• NIDA

Publications

None provided.

• Responsible Party: Perry Renshaw, Professor of Psychiatry, University of Utah
• ClinicalTrials.gov Identifier: NCT00950352
• Other Study ID Numbers: 32808; CDP-1212
• First Posted: Jul 31, 2009
• Last Update Posted: Feb 11, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Perry Renshaw, Professor of Psychiatry, University of Utah: methamphetamine; Citicoline; CDP-Choline; Neuroimaging; MRI; Brain; MRS; DTI
• Additional relevant MeSH terms: Choline; Cytidine Diphosphate Choline

Study Results

Participant Flow

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	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.	32 subjects with methamphetamine dependence were treated with placebo for 8-9 weeks. Placebo: Subjects were given 1 g of placebo twice daily for 8-9 weeks. They will be taking the same quantity as the citicoline group.
Period Title: Overall Study
STARTED	72	32
COMPLETED	30	21
NOT COMPLETED	42	11

Baseline Characteristics

Arm/Group Title	Citicoline	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	72	32	104
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	72 100%	32 100%	104 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.9 (6.8)	31.4 (7.1)	32.4 (6.89)
Sex: Female, Male (Count of Participants)
Female	33 45.8%	14 43.8%	47 45.2%
Male	39 54.2%	18 56.3%	57 54.8%
Region of Enrollment (participants) [Number]
United States	72 100%	32 100%	104 100%

Outcome Measures

1. Primary Outcome

Title	Methamphetamine Dependent Subjects Treated With Citicoline vs Placebo
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citicoline	Placebo
Arm/Group Description	Subjects will be given 1g citicoline twice daily for a total of 8-9 weeks.	Subjects will be given 1 g of placebo twice daily for 8-9 weeks. They will be taking the same quantity as the citicoline group.
Measure Participants	30	21
Mean (Standard Deviation) [total amount consumed in grams]	0.3025 (0.16498)	0.3850 (0.34547)

2. Secondary Outcome

Title	Testing if Citicoline Administration Will be Associated With Significant Improvements in Neuropsychological Performance.
Description	Cognitive measurement tests will be employed.
Time Frame	Neuropsychological testing will occur at week 0 and week 8/9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Testing if Improvements in Cognitive Function as Well as Brain Chemical and Structural Parameters Will be Associated With Greater Reductions in Drug Use.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Citicoline		Placebo
Arm/Group Description
All Cause Mortality
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/72 (2.8%)		0/32 (0%)
Infections and infestations
Sepsis	1/72 (1.4%)	1	0/32 (0%)	0
Psychiatric disorders
Suicide attempt	1/72 (1.4%)	1	0/32 (0%)	0
Other (Not Including Serious) Adverse Events
	Citicoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/72 (13.9%)		14/32 (43.8%)
Gastrointestinal disorders
Gatsrointestinal symptoms	2/72 (2.8%)	2	4/32 (12.5%)	4
General disorders
General (Weight loss, Headache, Cold/flu-lie symptoms, fatigue, pulmonary)	6/72 (8.3%)	6	6/32 (18.8%)	6
Psychiatric disorders
Psychiatric	2/72 (2.8%)	2	4/32 (12.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.