Actively Recruiting
31P-MRS and Functional Connectivity Study of 5-HTP and Creatine as Antidepressant Augmentation in SSRI/SNRI-Resistant Major Depressive Disorder
Led by University of Utah · Updated on 2025-08-08
106
Participants Needed
1
Research Sites
4 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This research aims to evaluate the effects of 5-hydroxytryptophan (5-HTP) and creatine monohydrate as augmenting agents for the treatment of major depressive disorder (MDD) that is resistant to standard antidepressants. The study focuses on addressing the potential impact of relative hypoxia on depression through alterations in brain bioenergetics and serotonin synthesis, investigating biological markers linked to depression and antidepressant response. This phase 2 trial involves participants diagnosed with MDD who have not fully responded to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Participants will be randomly assigned to one of three groups for 8 weeks: a low dose group receiving 5-HTP 100 mg twice daily plus creatine 5 g daily, a high dose group receiving 5-HTP 200 mg twice daily plus creatine 10 g daily, or a placebo group receiving matched placebos for both agents. The study will assess the biological and clinical effects of these treatments by measuring brain phosphorus magnetic resonance spectroscopy (31P-MRS), resting state functional connectivity imaging (fcMRI), and plasma serotonin levels, aiming to replicate and extend findings from an earlier phase. During the study, participants will undergo clinical assessments including the 17-item Hamilton Depression Rating Scale to monitor changes in depression severity, as well as secondary measures like the Montgomery-Asberg Depression Rating Scale. Brain imaging and blood tests will be conducted to evaluate changes in brain energy metabolism and serotonin. Safety monitoring includes screening for medical conditions and pregnancy, with study visits scheduled over the 8-week treatment period. The total duration of participation aligns with the treatment timeline, and the study uses quadruple masking to ensure unbiased results.
CONDITIONS
Brief Title
5-HTP and Creatine for Depression R33 Phase
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults age 18 to 65 years inclusive
- Current diagnosis of major depressive disorder confirmed by the MINI interview
- Hamilton Depression Rating Scale (HAM-D17) score of 16 or higher
- Adherence to an FDA-approved SSRI or SNRI antidepressant for at least 8 weeks
- Right-handed
- Living at an altitude above 4000 feet for at least 12 weeks
You will not qualify if you...
- Diagnosis of psychiatric conditions other than major depressive disorder or anxiety
- History or current diagnosis of kidney disease such as chronic or acute renal failure
- Current colitis or diverticulitis
- History or current pulmonary disease except well-controlled asthma
- Current smoking
- History of cardiac disease or corrected QT interval (QTc) over 500 ms
- History of fibromyalgia or any rheumatological condition
- History or current seizure disorder
- Current serious suicide risk
- Current use of antipsychotics, mood stabilizers, or non-SSRI/SNRI antidepressants except for bupropion or trazodone within specified doses
- Use of supplements other than standard multivitamins
- Pregnancy, positive pregnancy test, or inadequate birth control
- Previous or current serotonin syndrome
- Pre-existing eosinophilia (absolute eosinophil count over 500/uL)
- Contraindications for MRI such as ferromagnetic implants, implanted devices, or claustrophobia
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 8 weeks
Participants receive oral supplements of 5-hydroxytryptophan and creatine monohydrate or placebos as antidepressant augmentation while continuing their SSRI or SNRI treatment.
Weekly visits for up to 8 weeks
Trial Site Locations
Total: 1 location
1
University of Utah Department of Psychiatry
Salt Lake City, Utah, United States, 84108
Actively Recruiting
Research Team
B
Brent Kious, MD
H
Hailey Nielson, MS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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