Creatine Augmentation Treatment in Major Depressive Disorder Subjects

Efficacy and Safety of Augmentation of Creatine for the Patients With Major Depressive Disorder

Given 1) the established safety with short-term or long-term supplementation of Cr, 2) its potential usefulness in improving brain energy metabolism, 3) the reported abnormality in brain energy metabolism in MDD subjects, and 4) plausible association between depression and inflammatory mediators, we hypothesize that oral Cr augmentation will help reduce symptoms in MDD patients as well as normalize a deficit in brain energy metabolism and that improvement of MDD and brain energy metabolism will be correlated with inflammatory mediators changes.

In this study, we plan to conduct an randomized, double-blind, placebo-controlled augmentation study with creatine in addition to escitalopram. We will assess the efficacy and safety of the Cr augmentation and evaluate changes relevant to brain energy metabolism and inflammatory mediators.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Dietary supplement: Creatine monohydrate; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 137-701
    • Seoul st. mary's hospital
  • Seoul, Korea, Republic of
    • St. Paul's Hospital
  • Kyunggi-Do
    • Bucheon City, Kyunggi-Do, Korea, Republic of
      • Holy Family Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 19-65 year-old male or female
• Major depressive disorder diagnosed by SCID-IV
• Hamilton depression rating scale score >= 16 at screening
• Written informed consent

Exclusion Criteria:

• Suicidal idea that needs hospitalization
• Any other axis I psychiatric disorder
• Neurologic disease (eg., epilepsy, infarct, multiple sclerosis, brain tumor)
• IQ below 80
• Inflammatory disease including autoimmune disease
• Taking anti-inflammatory medication
• Serious physical disease
• Substance abuse or dependence history in recent 6 months
• Pregnant or having plan to be pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Creatine; The subjects with major depressive disorder, treated with creatine in addition to escitalopram	Dietary supplement: Creatine monohydrate; In addition to 10-20mg escitalopram, the subjects will be given total 3 gram of creatine (500mg/capsule) a day in first week and then, 5 gram a day in the rest of the weeks.
Placebo Comparator: Placebo; The subjects with major depressive disorder, treated with placebo in addition to escitalopram	Dietary supplement: Placebo; In addition to 10-20mg escitalopram, the subjects will be given total 6 capsules of placebo (equal quantities to those of creatine group) a day in first week and then, 10 capsules a day in the rest of the weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hamilton depression rating scale	baseline, 1st, 2nd, 4th, 8th week

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical global impression scale	baseline, 1st, 2nd, 4th, 8th week
Side effects assessment: the interview and examination by the investigators	baseline, 1st, 2nd, 4th, 8th week
Serum inflammatory mediators (eg., IL-1, -2, PGE2, interferon gamma) level	baseline, 8th week
Serum creatinine level	baseline, 2nd, 8th week
Brain MRI	baseline, 8th week
Montgomery-Asberg depression scale	baseline, 1st, 2nd, 4th, 8th week

Collaborators and Investigators

• Sponsor: Ewha Womans University
• Investigators: Study Chair: Perry F Renshaw, MD, PhD, University of Utah; Study Director: In Kyoon Lyoo, MD, PhD, MMS, Ewha Womans University

Publications and helpful links

General Publications

• Yoon S, Kim JE, Hwang J, Kim TS, Kang HJ, Namgung E, Ban S, Oh S, Yang J, Renshaw PF, Lyoo IK. Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder. Biol Psychiatry. 2016 Sep 15;80(6):439-447. doi: 10.1016/j.biopsych.2015.11.027. Epub 2015 Dec 15.
• Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry. 2012 Sep;169(9):937-945. doi: 10.1176/appi.ajp.2012.12010009.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: August 4, 2008
• First Submitted That Met QC Criteria: August 4, 2008
• First Posted (Estimate): August 7, 2008

Study Record Updates

• Last Update Posted (Actual): July 5, 2017
• Last Update Submitted That Met QC Criteria: July 3, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Efficacy; Augmentation; Major Depressive Disorder; Creatine; Brain Energy Metabolism
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: BIC-08DE00101B