NCT05895747 · University of Utah
5-HTP and Creatine for Depression R33 Phase
What this study is about
This is a three-armed clinical trial examining the effect of 5-hydroxytryptophan and creatine monohydrate as augmenting agents for the treatment of depression. Subjects will be randomly assigned between 5-HTP 100mg BID + creatine 5g daily, 5-HTP 200mg BID + creatine 10g daily, vs double placebo, for 8 weeks.
View original scientific description
This is a three-armed clinical trial examining the effect of 5-hydroxytryptophan and creatine monohydrate as augmenting agents for the treatment of depression. Subjects will be randomized between 5-HTP 100mg BID + creatine 5g daily, 5-HTP 200mg BID + creatine 10g daily, vs double placebo, for 8 weeks. The ability of the interventions to affect biomarkers associated with depression will be assessed using brain phosphorus magnetic resonance spectroscopy, functional connectivity imaging, and plasma serotonin levels.
Interventions
DRUG
Low Dose 5-hydroxytryptophan
5-hydroxytryptophan 100mg PO BID
DRUG
High Dose 5-hydroxytryptophan
5-hydroxytryptophan 200mg PO BID
DRUG
Low Dose Creatine Monohydrate
Creatine monohydrate 5g PO qday
DRUG
High Dose Creatine Monohydrate
Creatine monohydrate 10g PO qday
DRUG
Placebo
Creatine-matched placebo and 5-HTP-matched placebo; Placebo will be dextrose either encapsulated (5-HTP matched) or as loose powder (creatine matched)
Primary outcome measures
17-Item Hamilton Depression Rating Scale
Time frame: 8 weeks
Hamilton Depression Rating Scale response: \>=50% reduction in baseline score; maximum possible score is 52, minimum possible score is 0. Higher scores suggest more severe depression.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Adults age 18-65 years inclusive
- Current diagnosis of MDD identified by the MINI (Mini Neuropsychiatric Interview)
- Current HAM-D17 score of \>= 16
- Adequate adherence to any FDA approved SSRI or SNRI for at least 8 weeks
- Right-handed
- Residing at \> 4000 ft for at least 12 weeks
Exclusion criteria
- Any non-MDD and non-anxiety psychiatric diagnosis, as identified by the MINI
- History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease
- Current colitis or diverticulitis
- History of or current pulmonary disease (except well controlled asthma)
- Current smoking
- History of cardiac disease or QTc \> 500ms
- History of fibromyalgia or any rheumatological condition
- History of or current seizure disorder
- Current serious suicide risk identified by the Columbia Severity Suicide Rating Scale
- Current treatment with an antipsychotic, mood stabilizer, or non-SSRI/SNRI antidepressant except for bupropion at FDA-approved doses or trazodone up to 200mg, or use of any supplements apart from standard multivitamins
- Positive pregnancy test, pregnancy, failure to use adequate birth control method
- Previous diagnosis of serotonin syndrome or evidence of serotonin syndrome
- Pre-existing eosinophilia (absolute eosinophil count \> 500/uL)
- Contraindications to MRI: ferromagnetic implants, implanted devices, claustrophobia
Where
- Salt Lake City, Utah
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 8, 2025 · Source of record for eligibility and locations