Clinical trial NCT02922725: Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression in Females
Official title: A Randomized, Double-blind, Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression Associated With Hypobaric Hypoxia in Females
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Major Depressive Disorder
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2016-10-04
Enrollment: 32
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose to determine if 8 weeks of dietary augmentation with oral 5g creatine monohydrate daily and 100 mg of 5-hydroxytryptophan (5-HTP) twice daily reduces hypoxia-related depressive symptoms measured by the 17-item Hamilton Depression Rating Scale (HAM-D) in women with SSRI- or SNRI-resistant depression, combined with the examination of changes in functional connectivity based on resting-state fMRI and changes in brain metabolism inferred from phosphorus-31 magnetic resonance spectroscopy.

Detailed description: Serotonin and creatine are processed separately in the brain, and deficits in these brain biochemicals lead to distinct clinical problems. Therefore, investigators believe that treatment with a combination therapy, which could correct both deficits, would have a synergistic effect in the treatment of hypoxia-related depression and possibly other forms of treatment-resistant depression. Thus, investigators propose to investigate antidepressant efficacy of dietary 5-hydroxytryptophan (5-HTP) and creatine, as a means to restore the brain neurotransmitter and metabolic imbalances linked to chronic hypoxia caused by high altitude residence.

Eligibility criteria: Inclusion Criteria:

* Female gender, ages 25-40 years inclusive
* Current diagnosis of Major Depressive Disorder identified by the SCID-I
* Current HAM-D17 score of \> 16
* Adequate adherence to any FDA approved SSRI or SNRI for at least 8 weeks
* Right-handed

Healthy Controls Inclusion criteria:

* Female gender, ages 25-40 inclusive
* No current or past DSM-5 diagnosis, as determined by clinical and structured interviews

Exclusion Criteria:

* Any non-MDD and non-anxiety psychiatric diagnosis, as identified by the SCID-I
* History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease
* Diabetes type I or II
* Current colitis or diverticulitis
* History of or current pulmonary disease
* History of cardiac disease or QTc \> 500ms
* History of fibromyalgia, lupus, eosinophilia-myalgia syndrome, dermatomyositis, polymyositis, rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, ankylosing spondylitis, or other related 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 antidepressant
* Positive pregnancy test, pregnancy, failure to use adequate birth control method
* Previous diagnosis of serotonin syndrome or evidence of serotonin syndrome
* Use of any excluded drugs or medications including serotonergic drugs or medications (Table 2)
* Pre-existing eosinophilia (absolute eosinophil count \> 500/uL)
* Contraindications to MRI: ferromagnetic implants, implanted devices, claustrophobia

Primary outcomes:
measure: Change From Baseline in Hamilton Depression Rating Scale
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: