A Randomized Double-Blind Controlled Trial of Creatine in Female Methamphetamine Users

Phase 4

Completed

Conditions: Dual Diagnosis
Drug Addiction
Depression

Interventions: Drug: Creatine monohydrate

Registration Number: NCT02192931

Lead Sponsor: Perry Renshaw

Brief Summary: Methamphetamine (MA) addiction is a public health concern that causes substantial harm to individual users, and imposes an economic burden in the U.S. totaling up to $48.3 billion annually. This study proposes to address a critical aspect of this problem: the lack of any proven, FDA-approved pharmacological treatments for MA users. The proposal combines an intervention designed to improve energy metabolism in the brain, and a neuroimaging technique capable of measuring the neurochemicals that represent cerebral bioenergetic function. The study will replicate and extend a key neuroimaging finding from the investigators recent MA studies: that MA users have decreased phosphocreatine (PCr) levels in the brain, compared to healthy volunteers. Phosphocreatine is the substrate reservoir for the creatine kinase reaction, which reversibly converts PCr into adenosine triphosphate (ATP), the brain's major energy supply, and creatine. Neuronal energy demands are met through a shift in reaction equilibrium, which is designed to maintain the concentration of ATP constant. Research results from the investigators recent study also showed that female MA users have lower brain PCr levels compared to male users. These findings join the converging lines of evidence that MA use is associated with mitochondrial dysfunction, i.e. deficient energy metabolism, in the brain. Frequently, MA users also experience depression, as well as cognitive deficits. Interestingly, both of these entities are also linked to mitochondrial dysfunction in the brain.

The long-term goal of this research program is to define the alterations in brain chemistry that underlie MA use disorders, and to utilize translational magnetic resonance spectroscopy (MRS) neuroimaging to identify rational brain-based treatment targets. Once a hypothesis-driven intervention is identified, MRS can then be further employed in treatment studies, to verify that "target engagement" is achieved. The specific aims of this proposal are an example of this stepwise scientific process: the nutritional supplement creatine will be tested in a randomized, placebo-controlled study of women with MA use disorders, to investigate creatine's effect on cerebral PCr levels, depressive symptoms, and MA usage.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 65

Inclusion Criteria

Female gender, ages 18-55 inclusive
Current primary diagnosis of MA dependence or abuse, with MA preferred drug of abuse
Current diagnosis of Major Depressive Disorder
Current HAMD score > 15
Clinical Global Impressions Severity depression score > 4
If currently taking a psychotropic medication for depressed mood, regimen must be stable for > 4 weeks before randomization

Exclusion Criteria

Persons unable to provide adequate consent
Persons who are at clinically significant suicidal or homicidal risk
Primary substance-related diagnosis other than MA dependence or abuse
Comorbid substance dependence diagnosis, other than nicotine (substance abuse diagnoses are not excluded)
Positive pregnancy test
Positive test for the antibody to the Human Immunodeficiency Virus (HIV)
History of renal disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Creatine monohydrate	Creatine monohydrate	5 grams of daily creatine monohydrate for 8 weeks
Placebo	Creatine monohydrate	5 g of placebo for 8 weeks

Primary Outcome Measures

Name	Time	Method
Hamilton Depression Rating Scale (HAMD) Scores	8-weeks	Change in Hamilton Depression Rating Scale (HAMD) scores will be evaluated over the course of the 8-week treatment period. The HAMD provides an indication of depression and over time provides a valuable guide to progress. Total score ranges from 0 to 54. 0 means no depression and 24 and above means severe depression.

Secondary Outcome Measures

Name	Time	Method
Beck Anxiety Inventory (BAI) Scores	8-weeks	Change in Beck Anxiety Inventory (BAI) scores will be evaluated over the course of the 8-week treatment period. The BAI aims to assess the severity of anxiety symptoms, helping clinicians and researchers understand the level of anxiety an individual is experiencing. 0 means minimal anxiety and 30-63 means severe anxiety. The scale ranges from 0 to 63. Total score is reported.