Major Depressive Disorder
Conditions
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.
Interventions
DRUG5-hydroxytryptophan and Creatine
OTHERPlacebo control
Sponsors
Brent Michael Kious, MD, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamilton Depression Rating Scale | 8 weeks | The total Hamilton Depression (HAM-D) Rating Scale provides and indication of depression In general, the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe. Range: 0 to 54 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Depressed Patients Receiving Study Drug Participants diagnosed with MDD
5-hydroxytryptophan and Creatine | 11 |
| Depressed Patients Receiving Placebo Participants diagnosed with MDD
Placebo control | 12 |
| Healthy Controls Participants with no history of MDD
No intervention | 8 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Depressed Patients Receiving Study Drug | Depressed Patients Receiving Placebo | Total | Healthy Controls |
|---|---|---|---|---|
| 17-Item Hamilton Depression Rating Scale | 20.5 units on a scale STANDARD_DEVIATION 3.4 | 20.1 units on a scale STANDARD_DEVIATION 2.9 | 20.3 units on a scale STANDARD_DEVIATION 3.3 | — |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 31 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 31 Participants | 8 Participants |
| Region of Enrollment United States | 11 Participants | 12 Participants | 31 Participants | 8 Participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 31 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 0 / 8 |
| other Total, other adverse events | 0 / 11 | 0 / 12 | 0 / 8 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 8 |
Outcome results
Primary
Change From Baseline in Hamilton Depression Rating Scale
The total Hamilton Depression (HAM-D) Rating Scale provides and indication of depression In general, the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe. Range: 0 to 54
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Depressed Patients Receiving Study Drug | Change From Baseline in Hamilton Depression Rating Scale | 6.8 units on a scale | Standard Deviation 5.5 |
| Depressed Patients Receiving Placebo | Change From Baseline in Hamilton Depression Rating Scale | 7.3 units on a scale | Standard Deviation 5.4 |