Recruiting
Phase 2

5-HTP & Creatine

Sponsor:

University of Utah

Code:

NCT05895747

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Low Dose 5-hydroxytryptophan

High Dose 5-hydroxytryptophan

Low Dose Creatine Monohydrate

High Dose Creatine Monohydrate

Placebo

Study Details

Brief summary:

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.

Conditions

Major Depressive Disorder

Study ID

NCT05895747

Start date

Sep 28, 2023

Status verified date

Aug, 2026

Completion date

Sep 30, 2027

Anticipated

Primary completion date

Jul 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

106 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Low Dose 5-hydroxytryptophan and Creatine Monohydrate

5-HTP 100mg PO BID plus creatine 5g PO Qday

experimental: High Dose 5-hydroxytryptophan and Creatine Monohydrate

5-HTP 200mg PO BID plus creatine 10mg PO Qday

placebo comparator: Double Placebo

Creatine-matched placebo and 5-HTP-matched placebo

Interventions

Low Dose 5-hydroxytryptophan

5-hydroxytryptophan 100mg PO BID

High Dose 5-hydroxytryptophan

5-hydroxytryptophan 200mg PO BID

Low Dose Creatine Monohydrate

Creatine monohydrate 5g PO qday

High Dose Creatine Monohydrate

Creatine monohydrate 10g PO qday

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 measure

  • 17-Item Hamilton Depression Rating Scale [ Time Frame: 8 weeks ]

Central Contacts and Locations

Central contacts

Brent Kious, MD

8015851418brent.kious@hsc.utah.edu

Hailey Nielson, MS

801-581-3475hailey.nielson@utah.edu

Locations

University of Utah Department of Psychiatry

Recruiting

Salt Lake City, Utah, United States, 84108

Contacts

Brent Kious

8015851418brent.kious@hsc.utah.edu

More Information

Sponsor

University of Utah

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Utah on 2026-08-27.