Creatine Augmentation in Veterans With SSRI-Resistant Major Depression
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Creatine Augmentation in Female & Male Veterans With Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder|
- 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
- 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
|Study Start Date:||September 2012|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Open-Label Active Treatment with Creatine 5 grams daily for 8 weeks.
Oral Creatine 5 grams daily.
Other Name: Creapure
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01175616
|Study Director:||Perry F Renshaw, MD, PhD, MBA||University of Utah|