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Creatine Augmentation in Veterans With SSRI-Resistant Major Depression

This study has been withdrawn prior to enrollment.
(Study withdrawn from ClinicalTrials.gov.)
Sponsor:
Information provided by (Responsible Party):
Douglas Kondo, MD, University of Utah
ClinicalTrials.gov Identifier:
NCT01175616
First received: August 3, 2010
Last updated: August 11, 2016
Last verified: August 2016

August 3, 2010
August 11, 2016
September 2012
April 2014   (final data collection date for primary outcome measure)
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score [ Time Frame: screening; baseline; weeks 1, 2, 4, 5, 8, and 10 ] [ Designated as safety issue: No ]
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
Change in the Montgomery Asberg Depression Rating Scale (MADRS) score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
The primary clinical outcome measure will be the change in MADRS; response will be defined as a 50% or more decrease in MADRS score from baseline and a Clinical Global Impression (CGI) improvement score of 1 or 2.
Complete list of historical versions of study NCT01175616 on ClinicalTrials.gov Archive Site
Changes in 3T 31Phosphorus Magnetic Resonance Spectroscopy metabolites [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
The primary neuroimaging outcome measures will be changes in 3T 31P-MRS metabolites (PCr and β-NTP) globally and in the anterior cingulate cortex
Changes in 3T 31P-MRS metabolites [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
The primary neuroimaging outcome measures will be changes in 3T 31P-MRS metabolites (PCr and b-NTP) globally and in the anterior cingulate cortex.
Not Provided
Not Provided
 
Creatine Augmentation in Veterans With SSRI-Resistant Major Depression
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.

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.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Major Depressive Disorder
Drug: Creatine
Oral Creatine 5 grams daily.
Other Name: Creapure
Experimental: Creatine
Open-Label Active Treatment with Creatine 5 grams daily for 8 weeks.
Intervention: Drug: Creatine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
April 2014
April 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
United States
 
NCT01175616
00041936
Yes
No
The study was closed prior to human subjects receiving investigational treatment.
Douglas Kondo, MD, University of Utah
University of Utah
Not Provided
Study Director: Perry F Renshaw, MD, PhD, MBA University of Utah
University of Utah
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP