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

NCT02192931 | Completed Phase 4 Results DMC

• 1 other identifier: 73034
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Dual Diagnosis; Drug Addiction

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale (HAMD) Scores

  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.

  8-weeks

Secondary Outcomes (1)

• Beck Anxiety Inventory (BAI) Scores

  8-weeks

Other Outcomes (2)

• BL Neurochemistry Measured by Magnetic Resonance Spectroscopy

  Baseline

• Neurochemistry Measured by Magnetic Resonance Spectroscopy TX

  8-weeks

Study Arms (3)

Creatine monohydrate

ACTIVE COMPARATOR

5 grams of daily creatine monohydrate for 8 weeks

Drug: Creatine monohydrate

Placebo

PLACEBO COMPARATOR

5 g of placebo for 8 weeks

Drug: Creatine monohydrate

Healthy Control

NO INTERVENTION

Interventions

Creatine monohydrate DRUG

Creatine monohydrate; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Perry Renshaw: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84108, United States

Location

MeSH Terms

Conditions

Depression; Substance-Related Disorders

Interventions

Creatine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Danielle Boxer
• Organization: University of Utah

danielle.boxer@utah.edu

801-587-1549

Study Officials

• Perry Renshaw, MD, PhD, MBA

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: July 17, 2014
• Study Start: September 1, 2014
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: April 8, 2025
• Results First Posted: April 8, 2025

Record last verified: 2025-03

Locations

US (1)