Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Creatine Treatment for Female Adolescents With Depression Who Are Non-Responders to Fluoxetine or Escitalopram

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00851006
Recruitment Status : Completed
First Posted : February 25, 2009
Results First Posted : January 13, 2015
Last Update Posted : May 12, 2017
Sponsor:
Collaborator:
AlzChem, LLC
Information provided by (Responsible Party):
Douglas Kondo, MD, University of Utah

Tracking Information
First Submitted Date  ICMJE February 23, 2009
First Posted Date  ICMJE February 25, 2009
Results First Submitted Date  ICMJE December 9, 2014
Results First Posted Date  ICMJE January 13, 2015
Last Update Posted Date May 12, 2017
Study Start Date  ICMJE April 2009
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2015)
Mean Children's Depression Rating Scale (CDRS-R) [Reference: Poznanski EO et al. Preliminary Studies of the Reliability and Validity of the Children's Depression Rating Scale. J Am Acad Child Psychiatry. 1984 Mar;23(2):191-7.] [ Time Frame: 8 weeks ]
The CDRS-R is a 17-item scale, with items ranging from 1 to 5 or 1 to 7 (possible total score from 17 to 113), rated by a clinician via interviews with the child or parent. Scores ≥40 are indicative of depression, whereas scores ≤28 is often used to define remission
Original Primary Outcome Measures  ICMJE
 (submitted: February 24, 2009)
The primary clinical outcome measure will be the change in CDRS-R; response will be defined as a > 50% decrease in CDRS-R score from baseline and a CGI improvement score of 1 or 2. [ Time Frame: 6 weeks ]
Change History Complete list of historical versions of study NCT00851006 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2015)
31-phosphorus Magnetic Resonance Spectroscopy Phosphocreatine Metabolite [ Time Frame: 8 weeks ]
Phosphocreatine Metabolite is a phosphorylated creatine molecule that plays a role in the production of the energy in the body. Phosphocreatine (PCr) metabolite was quantified by calculating the ratio of PCr over total phosphorus resonance from 31-Phosphorus Magnetic Resonance Spectroscopy.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2009)
MRI volumetric measurements (i.e. VBM and morphometric analyses). [ Time Frame: 6 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Creatine Treatment for Female Adolescents With Depression Who Are Non-Responders to Fluoxetine or Escitalopram
Official Title  ICMJE Adjunctive Creatine Treatment for Adolescent Females With Major Depressive Disorder Who Are Non-Responders to Fluoxetine or Escitalopram: A Magnetic Resonance Spectroscopy Study
Brief Summary

The purpose of this study is to see if creatine, which is a naturally occurring chemical in the body, is effective for treating Major Depressive Disorder (MDD) in female teenagers. Creatine may have effects of interest in the brain. The reason for the MRI component of this study is to learn about new ways to see inside the brain. The investigators will use magnetic fields and radio waves to look at the brain and chemicals in the brain. The investigators hope that this technique will have medial use in the future.

The primary hypothesis of the study is that oral creatine supplementation will have a beneficial effect as adjunctive therapy in female adolescents with MDD who are non-responders to an adequate trial of the SSRIs Fluoxetine or Escitalopram.

Detailed Description This is an open-label clinical trial of the investigational drug creatine, for augmentation treatment of female adolescents with Major Depressive Disorder (MDD) who have failed to respond to first-line treatment with Fluoxetine or Escitalopram. Widely used by high school and college athletes in the U.S., creatine is an over-the-counter nutritional supplement with annual sales of more than $200 million. Studies in animals show that creatine improves the performance of female rats in the Porsolt Forced Swim test, which is used to predict the efficacy antidepressant compounds. Human neuroimaging studies indicate that patients with MDD have abnormal levels of high-energy phosphate metabolites in brain, primarily adenosine triphosphate (ATP) and phosphocreatine. Research has also shown that creatine supplementation induces changes in these high-energy phosphate metabolites that are associated with a positive response to antidepressants. For the proposed study, ten female adolescents between the ages of 13-18 with MDD will be recruited for participation in an open-label trial of creatine. Participants with depression will have unremitted MDD despite treatment with Fluoxetine at a dose > 40mg daily for > 4 weeks or Escitalopram at a dose of > 10 mg daily for > 4 weeks. Depressed participants will be treated with oral creatine 4gm daily for eight weeks, and will continue to take Fluoxetine or Escitalopram as prescribed. In addition, ten healthy control participants with no history of psychiatric or substance abuse disorder will be recruited. No treatment will be administered to the control participants. The primary outcome measure will be the Children's Depression Rating Scale (CDRS-R), which was used in the Treatment for Adolescents with Depression Study (TADS) clinical trial (March et al., JAMA 2004; 292(7):807-20) and the Treatment of Resistant Depression in Adolescents (TORDIA) study (Brent et al., JAMA 2008;299(8):901-13). All study participants will undergo brain scans at baseline and again after six weeks, with 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The brain scans will be used to measure high-energy phosphate metabolites in the Anterior Cingulate Cortex (ACC), an anatomical region of the brain that has been implicated in MDD. 31P-MRS is a non-invasive neuroimaging technique that does not expose participants to radiation. At the magnetic field strength utilized (3T), magnetic resonance imaging is FDA-approved and has no known adverse effects. 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 metabolite levels will be conducted in the MDD participants. The primary hypothesis of the study is that oral creatine will show efficacy as an augmentation treatment for female adolescents with MDD whose depression has not responded to Fluoxetine or Escitalopram. Secondary hypotheses include the following: adolescents with treatment-resistant MDD will show differences at baseline from healthy controls in high-energy phosphate metabolites in the ACC; and that brain scans in depressed adolescents who respond to creatine will show normalization of high-energy phosphate metabolites in the ACC.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE Drug: Creatine Monohydrate
Creapure brand of creatine monohydrate
Other Name: Creapure
Study Arms  ICMJE Experimental: Open-Label Creatine
Creatine Monohydrate 4 grams daily by mouth
Intervention: Drug: Creatine Monohydrate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 8, 2015)
13
Original Estimated Enrollment  ICMJE
 (submitted: February 24, 2009)
20
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria for Major Depressive Disorder Participants:

  • Participants must meet DSM-IV-TR criteria for Major Depressive Disorder, with current mood state depressed for ≥ 2 weeks.
  • Participants must be females
  • Participants must be between the age of 13 and 18 years.
  • Participants must have had an adequate trial of fluoxetine, defined as a trial of ≥ 8 weeks of treatment, with a dose of ≥ 40mg daily for ≥ 4 weeks. If the participant had a trial of 40mg daily and was unable to tolerate it, a dose of 20mg for ≥ 8 weeks is acceptable; OR
  • Participants must have had an adequate trial of escitalopram, defined as a trial of ≥ 8 weeks of treatment, with a dose of ≥ 20 mg daily for ≥ 4 weeks. If the participant had a trial of 20 mg daily and was unable to tolerate it, a dose of 10 mg for ≥ 8 weeks is acceptable.
  • Participants must have a CDRS-R score of ≥ 40 and a CGI-S score of ≥ 4.
  • Participants must be able to give informed consent or assent, and where applicable, parent(s)/guardian(s) must be able to give informed permission for study participation.

Inclusion Criteria for Healthy Control Participants:

  • Participants must be females
  • Participants must be between the age of 13 and 18 years.
  • Participants must not meet DSM-IV-TR diagnostic criteria for a psychiatric or substance abuse disorder.
  • Participants must be able to give informed consent or assent and, where applicable, parent(s)/guardian(s) must be able to give informed permission for study participation.

Exclusion Criteria for Treatment-Resistant Major Depressive Disorder Participants:

  • Unstable co-morbid medical, neurological or psychiatric disorder.
  • Pre-existing renal disease.
  • Proteinuria or microalbuminuria.
  • Pregnant females, nursing mothers, or females of childbearing potential who are unable or unwilling to practice birth control during the study. Participants who are of child-bearing potential must have a negative urine pregnancy test before each MRI/MRS brain scan.
  • High risk for suicidal behavior, homicidal behavior or self-harm.
  • Adolescents who are unlikely to be able to comply with the study protocol.
  • DSM-IV-TR criteria for current substance abuse or substance dependence, with the exception of nicotine abuse or dependence.
  • Contraindication to MRI/MRS brain scans, such as ferromagnetic implants or claustrophobic anxiety.
  • Documented or suspected history of intellectual disability (Full-Scale I.Q. < 70).
  • History of hypersensitivity to creatine monohydrate.

Exclusion Criteria for Healthy Controls:

  • Clinically significant psychiatric or substance abuse disorder.
  • Unstable medical or neurological illness.
  • Pregnancy, due to the unknown effects of MRI/MRS scanning on a developing fetus.
  • Females of childbearing potential who are unable or unwilling to practice contraception during the study.
  • Positive urine pregnancy test.
  • Contraindication to MRI/MRS scanning, such as ferromagnetic implant or claustrophobic anxiety.
  • Documented or suspected history of mental retardation (Full-Scale I.Q. < 70).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 13 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00851006
Other Study ID Numbers  ICMJE 33465
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Douglas Kondo, MD, University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE AlzChem, LLC
Investigators  ICMJE
Principal Investigator: Douglas G Kondo, MD University of Utah
PRS Account University of Utah
Verification Date April 2017

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