Major Depressive DisorderPhase 4NCT02134808
Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder
A Phase 4 study testing Creatine in people with Major Depressive Disorder, run by Perry Renshaw at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 21 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Creatine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2014to 27 Jun 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 to 21 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
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- 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].
- Participants must be able to grant informed consent (age > 18), or parent/guardian permission plus participant assent (age < 18).
- Participants must be female.
- Participants must be between the ages of 12 and 21 years.
- Participants must not meet DSM criteria for a current psychiatric illness or substance use disorder.
- Participants must have a CDRS-R score < 30.
Who cannot join
- 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.
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- 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.
- Worsening depression, as demonstrated by an increase in CDRS-R or MADRS score > 25% from baseline.
- Positive pregnancy test.
- A significant change to the participant's medication or psychotherapy treatment from the regimen reported at their baseline/screening visit (e.g. if the SSRI is discontinued).
- Incarceration, as the study is not approved to conduct "Research Involving Prisoners."
- If a clinically-significant intracranial lesion is found by the Radiologist on a participant's baseline brain scan, they will be withdrawn from the study and referred for appropriate medical care.
- The principal investigator retains the right to withdraw participants from the study without their permission, in the event they are unwilling or unable to maintain adherence with the research protocol.
- HEALTHY COMPARISON SUBJECTS
- Unstable medical or neurological illness.
- Clinically-significant psychiatric or substance use disorder.
- Pregnant subjects, due to the unknown effects of MRI/MRS scans on a fetus. In addition, women of childbearing potential who are unable or unwilling to practice contraception during the study will be excluded. Female participants who are of childbearing potential must have a negative urine pregnancy test before the MRI/MRS scan.
- Participants with a contraindication to MRI/MRS scanning, such as a metallic implant.
- Study Withdrawal Criteria:
- Withdrawal of parental permission or participant assent.
- Onset of a psychotic disorder or depression.
- Positive pregnancy test.
- A significant change to the participant's medication or psychotherapy treatment from the regimen reported at their baseline/screening visit, unless directed by the principal investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Utah School of Medicine
Salt Lake City, Utah, 84108
About this study
Official title: Placebo-Controlled Trial of Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder: a Magnetic Resonance Spectroscopy Study
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.
Read the detailed description
The current protocol seeks to expand upon the investigators previous work by opening recruitment on a pilot study of creatine 10g daily vs. placebo as a treatment for female adolescents with SSRI-resistant MDD. The purpose of the pilot study is twofold: A) to evaluate several aspects of the feasibility of creatine supplementation as a treatment for this population; and B) to estimate the effect size of adjunctive creatine, to inform the design and implementation of a potential future efficacy trial.
- Conditions
- Major Depressive Disorder
- Being tested
- Creatine, Placebo
- Keywords
- Major Depressive Disorder, Creatine, Brain Chemistry, Magnetic Resonance Spectroscopy, Treatment Resistance, Selective Serotonin Reuptake Inhibitor (SSRI) Resistance
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CreatineDrug
Also called Creatine Monohydrate
Creatine is a nutritional supplement.
PlaceboDrug
Also called Placebo Control
The placebo is an inactive ingredient similar in appearance, weight and density to the active treatment.
| Study group | Role | What they receive |
|---|---|---|
| Creatine | Active comparator | Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks. Receives: Drug: Creatine |
| Placebo | Placebo comparator | Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 8 weeks
Secondary outcomes (1)
Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS)
The Children's Depression Rating Scale-Revised (CDRS-R) and Montgomery-Asberg Depression Rating Scale (MADRS) will be administered to understand the severity of depressive symptoms, and how these symptoms change throughout the course of the study. The CDRS-R has a range of minimum score 17 and maximum score 113, with higher scores indicating more severe depression. The MADRS has a range of 0 to 60 with higher scores indicating more severe depressive symptoms.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study start21 Nov 2014
- Primary completion27 Jun 2017
- Study completion27 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Perry Renshaw
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Perry Renshaw, University of Utah
- Investigators
- Douglas Kondo, MD, Study director, University of UtahPerry F Renshaw, MD, PhD, MBA, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134808
- Sponsor's protocol ID
- 00073442
- Status last verified
- Jun 2024
- First submitted
- 6 May 2014
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 21831448
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-Controlled Trial of Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder: a Magnetic Resonance Spectroscopy Study
- ClinicalTrials.gov ID
- NCT02134808
- Acronym / sponsor ID
- 00073442
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, Creatine, Brain Chemistry, Magnetic Resonance Spectroscopy, Treatment Resistance, Selective Serotonin Reuptake Inhibitor (SSRI) Resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Perry RenshawUniversity, hospital or other
- Study start
- 21 Nov 2014 (actual)
- Primary completion
- 27 Jun 2017 (actual)
- Study completion
- 27 Jun 2017 (actual)
- First posted
- 9 May 2014 (estimated)
- Results
- Posted 3 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The current protocol seeks to expand upon the investigators previous work by opening recruitment on a pilot study of creatine 10g daily vs. placebo as a treatment for female adolescents with SSRI-resistant MDD. The purpose of the pilot study is twofold: A) to evaluate several aspects of the feasibility of creatine supplementation as a treatment for this population; and B) to estimate the effect size of adjunctive creatine, to inform the design and implementation of a potential future efficacy trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Creatine | Active comparator | Drug: CreatineSubjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks. |
Who may qualify
- Ages
- 12 to 21 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (31 listed)
- 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.
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: Creatine MonohydrateCreatine is a nutritional supplement. | Drug | Creatine |
| PlaceboAlso: Placebo ControlThe placebo is an inactive ingredient similar in appearance, weight and density to the active treatment. | Drug | Placebo |
Primary outcome
Brain Phosphocreatine (PCr) Concentrations
Time frame: Baseline and 8 weeks
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.
1 secondary outcome
Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
- Individual participant dataSharing planned: Undecided
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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.
Douglas Kondo, MD study director
University of Utah
Perry F Renshaw, MD, PhD, MBA principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Creatine in people with Major Depressive Disorder, run by Perry Renshaw at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 31 exclusion criteria. 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: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 3 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Brain Phosphocreatine (PCr) Concentrations (time frame: Baseline and 8 weeks). 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 NCT02134808, which also lists 1 linked publication.
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 3 Jul 2024.