Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder

NCT02134808 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 00073442
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The primary hypothesis is that compared to placebo, 10g of daily creatine monohydrate for eight weeks will be associated with significant increases in frontal lobe phosphocreatine and beta-nucleoside triphosphate (β-NTP) concentrations. A secondary hypothesis is that decreased depressive symptoms measured with the Children's Depression Rating Scale-Revised (CDRS-R) and Montgomery-Asberg Depression Rating Scale (MADRS) will be reciprocally correlated with increased β-NTP concentrations.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Creatine; Brain Chemistry; Magnetic Resonance Spectroscopy; Treatment Resistance; Selective Serotonin Reuptake Inhibitor (SSRI) Resistance

Outcome Measures

Primary Outcomes (1)

• Brain Phosphocreatine (PCr) Concentrations

  PCr will be measured through phosphorus magnetic resonance spectroscopy (31P-MRS). This will be performed in a 3 Tesla magnetic resonance imaging (MRI) scanner. Creatine concentration before and after treatment. By convention, 31P MRS data are typically reported as metabolite ratios.

  Baseline and 8 weeks

Secondary Outcomes (1)

• Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS)

  8 weeks

Study Arms (2)

Creatine

ACTIVE COMPARATOR

Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks.

Drug: Creatine

Placebo

PLACEBO COMPARATOR

Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks.

Drug: Placebo

Interventions

Creatine DRUG

Creatine is a nutritional supplement.

Also known as: Creatine Monohydrate

Creatine

Placebo DRUG

The placebo is an inactive ingredient similar in appearance, weight and density to the active treatment.

Also known as: Placebo Control

Placebo

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must be female.
• Participants must be able to grant informed consent (age \>18), or parent/guardian permission plus participant assent (age \<18).
• Participants must meet DSM criteria for Major Depressive Disorder (MDD), with current mood state depressed for \> 2 weeks.
• Participants must be between the ages of 12 and 21.
• Current CDRS-R raw score of \> 40 or MADRS score \> 25; and CGI-S score \> 3.
• Participants may be enrolled in individual and/or group psychotherapy, if it has been ongoing for at least 8 weeks.
• Participants must have been in treatment with an SSRI for at least 8 weeks, the last 4 of which were at a dosage of \> 20 mg per day of fluoxetine or its equivalent, e.g. 20 mg per day of paroxetine, 20 mg citalopram, 10 mg escitalopram, or 100 mg sertraline. If the participant attempted, but could not tolerate, a dose comparable to 20 mg fluoxetine, they will be considered eligible. (This definition of "Adolescent SSRI Resistant Depression" is modified from the NIH-sponsored, $17 million TORDIA Randomized Controlled Trial \[http://clinicaltrials.gov/ct2/show/NCT00018902\].

You may not qualify if:

• Unstable co-morbid medical, neurological, or psychiatric disorder.
• Current DSM criteria for substance abuse or dependence (excepting nicotine/cigarettes).
• Clinically significant suicidal or homicidal risk.
• Pre-existing renal disease.
• Proteinuria on baseline urinalysis testing.
• Pregnancy or breastfeeding.
• Sexually active and unwilling to practice contraception during the study.
• Contraindication to magnetic resonance imaging (e.g. ferromagnetic implant or claustrophobic anxiety).
• History of hypersensitivity to creatine.
• History of a previous failed therapeutic trial of creatine.
• Participants may be outpatients or inpatients, but incarcerated persons will be excluded because this study is not approved for "Research Involving Prisoners."
• Study Withdrawal Criteria:
• Withdrawal of parental permission, participant informed consent or participant assent.
• Onset of a psychotic disorder or bipolar disorder.
• Intolerable, or clinically-significant side effects to creatine.

Sponsors & Collaborators

• Perry Renshaw: lead

Study Sites (1)

University of Utah School of Medicine

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• Kondo DG, Sung YH, Hellem TL, Fiedler KK, Shi X, Jeong EK, Renshaw PF. Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study. J Affect Disord. 2011 Dec;135(1-3):354-61. doi: 10.1016/j.jad.2011.07.010. Epub 2011 Aug 9.

  PMID: 21831448 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Creatine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Douglas Kondo
• Organization: University of Utah

doug.kondo@hsc.utah.edu

(801) 587-1549

Study Officials

• Douglas Kondo, MD

  University of Utah

  STUDY DIRECTOR

• Perry F Renshaw, MD, PhD, MBA

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 9, 2014
• Study Start: November 21, 2014
• Primary Completion: June 27, 2017
• Study Completion: June 27, 2017
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-06

Locations

US (1)