Creatine Augmentation in Veterans With SSRI-Resistant Major Depression

August 11, 2016 updated by: Douglas Kondo, MD, University of Utah

Creatine Augmentation in Female & Male Veterans With Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 53 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Creapure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
screening; baseline; weeks 1, 2, 4, 5, 8, and 10

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline and 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Investigators

  • Study Director: Perry F Renshaw, MD, PhD, MBA, University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

August 3, 2010

First Submitted That Met QC Criteria

August 4, 2010

First Posted (Estimate)

August 5, 2010

Study Record Updates

Last Update Posted (Estimate)

August 15, 2016

Last Update Submitted That Met QC Criteria

August 11, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00041936

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

The study was closed prior to human subjects receiving investigational treatment.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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