Major Depressive DisorderPhase 4NCT01175616
Creatine Augmentation in Veterans With SSRI-Resistant Major Depression
A Phase 4 study testing Creatine in people with Major Depressive Disorder, run by University of Utah.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Creatine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2012to Apr 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
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.
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Major Depressive Disorder
- Being tested
- Creatine
- Keywords
- Depression, Adults
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CreatineDrug
Also called Creapure
Oral Creatine 5 grams daily.
| Study group | Role | What they receive |
|---|---|---|
| Creatine | Experimental | Open-Label Active Treatment with Creatine 5 grams daily for 8 weeks. Receives: Drug: Creatine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score
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
Measured: screening; baseline; weeks 1, 2, 4, 5, 8, and 10
Secondary outcomes (1)
Changes in 3T 31Phosphorus Magnetic Resonance Spectroscopy metabolites
The primary neuroimaging outcome measures will be changes in 3T 31P-MRS metabolites (PCr and β-NTP) globally and in the anterior cingulate cortex
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2010 (estimated)
- Study startSep 2012
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: Study withdrawn from ClinicalTrials.gov.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Douglas Kondo, MD, University of Utah
- Investigators
- Perry F Renshaw, MD, PhD, MBA, Study director, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01175616
- Sponsor's protocol ID
- 00041936
- Status last verified
- Aug 2016
- First submitted
- 3 Aug 2010
- Last updated
- 15 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: The study was closed prior to human subjects receiving investigational treatment.
Publications
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.
PubMed 22864465Kondo 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.
PubMed 21831448Allen PJ, D'Anci KE, Kanarek RB, Renshaw PF. Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats. Pharmacol Biochem Behav. 2012 Jun;101(4):588-601. doi: 10.1016/j.pbb.2012.03.005. Epub 2012 Mar 10.
PubMed 22429992Allen PJ. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value? Neurosci Biobehav Rev. 2012 May;36(5):1442-62. doi: 10.1016/j.neubiorev.2012.03.005. Epub 2012 Mar 24.
PubMed 22465051
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Creatine Augmentation in Female & Male Veterans With Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT01175616
- Acronym / sponsor ID
- 00041936
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, Adults
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn from ClinicalTrials.gov.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 5 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Creatine | Experimental | Drug: CreatineOpen-Label Active Treatment with Creatine 5 grams daily for 8 weeks. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CreatineAlso: CreapureOral Creatine 5 grams daily. | Drug | Creatine |
Primary outcome
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score
Time frame: screening; baseline; weeks 1, 2, 4, 5, 8, and 10
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
1 secondary outcome
Changes in 3T 31Phosphorus Magnetic Resonance Spectroscopy metabolites
Time frame: Baseline and 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2016.
- Background: PubMed 22864465Lyoo 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.
- Background: PubMed 21831448Kondo 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.
- Background: PubMed 22429992Allen PJ, D'Anci KE, Kanarek RB, Renshaw PF. Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats. Pharmacol Biochem Behav. 2012 Jun;101(4):588-601. doi: 10.1016/j.pbb.2012.03.005. Epub 2012 Mar 10.
- Background: PubMed 22465051Allen PJ. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value? Neurosci Biobehav Rev. 2012 May;36(5):1442-62. doi: 10.1016/j.neubiorev.2012.03.005. Epub 2012 Mar 24.
- Individual participant dataSharing planned: No. The study was closed prior to human subjects receiving investigational treatment.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Perry F Renshaw, MD, PhD, MBA study director
University of Utah
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Creatine in people with Major Depressive Disorder, run by University of Utah.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score (time frame: screening; baseline; weeks 1, 2, 4, 5, 8, and 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01175616, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2016.