5-HTP and Creatine for Depression R33 Phase

NCT05895747 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB_00132830_R33
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 17-Item Hamilton Depression Rating Scale

  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.

  8 weeks

Secondary Outcomes (1)

• Montgomery Asberg Depression Rating Scale

  8 weeks

Study Arms (3)

Low Dose 5-hydroxytryptophan and Creatine Monohydrate

EXPERIMENTAL

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

Drug: Low Dose 5-hydroxytryptophan; Drug: Low Dose Creatine Monohydrate; Drug: Placebo

High Dose 5-hydroxytryptophan and Creatine Monohydrate

EXPERIMENTAL

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

Drug: High Dose 5-hydroxytryptophan; Drug: High Dose Creatine Monohydrate

Double Placebo

PLACEBO COMPARATOR

Creatine-matched placebo and 5-HTP-matched placebo

Drug: Placebo

Interventions

Low Dose 5-hydroxytryptophan DRUG

5-hydroxytryptophan 100mg PO BID

Also known as: 5-HTP

Low Dose 5-hydroxytryptophan and Creatine Monohydrate

High Dose 5-hydroxytryptophan DRUG

5-hydroxytryptophan 200mg PO BID

Also known as: 5-HTP

High Dose 5-hydroxytryptophan and Creatine Monohydrate

Low Dose Creatine Monohydrate DRUG

Creatine monohydrate 5g PO qday

Also known as: creatine

Low Dose 5-hydroxytryptophan and Creatine Monohydrate

High Dose Creatine Monohydrate DRUG

Creatine monohydrate 10g PO qday

Also known as: creatine

High Dose 5-hydroxytryptophan and Creatine Monohydrate

Placebo DRUG

Creatine-matched placebo and 5-HTP-matched placebo; Placebo will be dextrose either encapsulated (5-HTP matched) or as loose powder (creatine matched)

Also known as: dextrose

Double Placebo; Low Dose 5-hydroxytryptophan and Creatine Monohydrate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah Department of Psychiatry

Salt Lake City, Utah, 84108, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

5-Hydroxytryptophan; Creatine; Glucose

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptophan; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Guanidines; Amidines; Organic Chemicals; Hexoses; Monosaccharides; Sugars; Carbohydrates

Central Study Contacts

Brent Kious, MD

CONTACT

8015851418; brent.kious@hsc.utah.edu

Hailey Nielson, MS

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 9, 2023
• Study Start: September 28, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)