Working… Menu

Creatine Augmentation in Veterans With SSRI-Resistant Major Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01175616
Recruitment Status : Withdrawn (Study withdrawn from
First Posted : August 5, 2010
Last Update Posted : August 15, 2016
Information provided by (Responsible Party):
Douglas Kondo, MD, University of Utah

Brief Summary:
The purpose of this study is to determine whether creatine will be helpful as an adjunctive treatment for treatment-resistant major depressive disorder (MDD) in female and male Veterans. We hypothesize that Veterans receiving creatine will show decreased depressive symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). We will also use 31-Phosphorus Magnetic Resonance Spectroscopy (31-P MRS) brain scans to compare levels of neurochemicals related to energy metabolism in the brain, before-and-after treatment with creatine, and between healthy controls and MDD participants.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Creatine Phase 4

Detailed Description:

This is an open-label clinical trial of the investigational drug creatine for augmentation treatment of female and male Veterans, ages 18-55, with Major Depressive Disorder (MDD) who have failed to respond to antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) drug. Based on converging preclinical and animal model research, and our laboratory's prior clinical trials, we hypothesize that the nutritional supplement creatine may provide benefit as an adjunctive treatment to SSRI pharmacotherapy, for Veterans with treatment-resistant depression.

Twenty (n=20) Veterans between the ages of 18-55 years with MDD will be recruited for participation in an open-label trial of creatine augmentation. Veterans with depression will have unremitted MDD, despite having had an adequate trial of an SSRI antidepressant. Participants with MDD will be treated with oral creatine 5 gm daily for 8 weeks and will continue taking their SSRI antidepressant. Participants will undergo brain scanning at baseline, and the scans will be repeated following 8 of adjunctive creatine.

The neuroimaging technique utilized is Phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS). 31P-MRS is a non-invasive method with no exposure to ionizing radiation. At the magnetic field strength utilized (3 Tesla), magnetic resonance imaging is FDA-approved and is not associated with irreversible or serious adverse events. Furthermore, 31P-MRS is the only in vivo method for in vivo quantification of phosphorus energy metabolism, in living human brain.

In addition to Veterans with MDD, twenty (n=20) healthy control (HC) participants will be recruited. HCs will be Veterans between the ages of 18-55, who have no history of psychiatric or substance use disorder. No treatment will be administered to HC participants.

The HCs will undergo a single 31P-MRS scan, which will be used to measure the phosphorus-bearing neurometabolites that are involved in brain energy metabolism. The research team will use data from 31P-MRS scans to compare levels of high-energy phosphate metabolites in MDD participants vs. healthy controls.

In addition, comparison of pre- and post-treatment 31P-MRS metabolite levels will be conducted in the MDD participants, to test the hypothesis that creatine augmentation improves brain energy metabolism.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Creatine Augmentation in Female & Male Veterans With Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder
Study Start Date : September 2012
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Creatine
Open-Label Active Treatment with Creatine 5 grams daily for 8 weeks.
Drug: Creatine
Oral Creatine 5 grams daily.
Other Name: Creapure

Primary Outcome Measures :
  1. Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score [ Time Frame: screening; baseline; weeks 1, 2, 4, 5, 8, and 10 ]
    The primary clinical outcome measure will be the change in MADRS; response will be defined as a 50% or greater decrease in MADRS score from baseline and a Clinical Global Impression Scale (CGI) improvement score of 1 or 2

Secondary Outcome Measures :
  1. Changes in 3T 31Phosphorus Magnetic Resonance Spectroscopy metabolites [ Time Frame: Baseline and 8 weeks ]
    The primary neuroimaging outcome measures will be changes in 3T 31P-MRS metabolites (PCr and β-NTP) globally and in the anterior cingulate cortex

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria for Major Depressive Disorder Participants:

  • Must be a U.S. military Veteran from 18-55 years of age.
  • Must meet DSM criteria for Major Depressive Disorder (MDD).
  • Current depressive episode duration of 4 weeks or longer.
  • Montgomery-Asberg Depression Rating Scale (MADRS) score of 18 or greater.
  • Adequate trial of an SSRI antidepressant, in terms of dosing and duration.
  • No change in SSRI dose, for 4 weeks prior to the baseline brain scan.
  • Partial or non-responder to current SSRI pharmacotherapy.

Exclusion Criteria for Major Depressive Disorder Participants:

  • Primary psychotic or schizophrenia-spectrum disorder.
  • Unstable co-morbid medical, neurologic, or psychiatric illness.
  • Clinically significant substance use disorder.
  • Significant risk of suicide, in the clinical judgment of the study physician.
  • Inability to provide informed consent.
  • Contraindication to brain scanning (e.g., pacemaker, ferromagnetic implant).
  • Pre-existing renal disease, with proteinuria at baseline.
  • History of hypersensitivity to creatine.
  • Concurrent participation in another FDA-sanctioned clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01175616

Sponsors and Collaborators
University of Utah
Layout table for investigator information
Study Director: Perry F Renshaw, MD, PhD, MBA University of Utah

Additional Information:
Layout table for additonal information
Responsible Party: Douglas Kondo, MD, MD, University of Utah Identifier: NCT01175616     History of Changes
Other Study ID Numbers: 00041936
First Posted: August 5, 2010    Key Record Dates
Last Update Posted: August 15, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The study was closed prior to human subjects receiving investigational treatment.
Keywords provided by Douglas Kondo, MD, University of Utah:
Additional relevant MeSH terms:
Layout table for MeSH terms
Depressive Disorder
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms