Depression
Conditions
Keywords
Depression, Medical food
Brief summary
The purpose of the study is to test whether oral 6(S)-5-MTHF (Deplin) is safe and effective in relieving depression when it is added to standard kinds of antidepressants called serotonin reuptake inhibitors (SSRIs).
Detailed description
The study consists of two phases, each lasting a total of four weeks (8 weeks total), with visits at the DCRP every 10 days. If the subject is eligible, they will be asked to return two weeks later for a baseline visit, when they will be randomly assigned, like a flip of a coin, to one of three treatment groups: a) drug/drug, b) placebo/drug, c) placebo/placebo (a placebo is a pill that looks like a study drug but contains no active medication). They will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. Neither the subject nor the research staff will know which group the subject is in. All subjects will be asked to take the study medication in the morning, in addition to their ongoing SSRI treatment.
Interventions
OTHER6(S)-5-MTHF(Deplin)
Deplin is a medical food. Patients will take 15 mg/day of deplin.
OTHERPlacebo
Inactive substance
Sponsors
Pamlab, L.L.C.
George I. Papakostas
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years old * Meet criteria for current Major Depressive Disorder * Currently taking an SSRI
Exclusion criteria
* Pregnant women * Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease * Prior course of MTHF augmentation, or intolerance to MTHF at any dose * Substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past) * Have failed more than 2 adequate antidepressant trials during the current Major Depressive Episode
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The 17-item Hamilton Depression Scale (HAM-D-17) | Baseline and Day 60 | The HAM-D-17 is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Items are scored on a scale of zero to four and higher scores indicate greater impairment. This scale is scored by summing the scores on each item and scores can range from 0-68. When assessing changes in HAMD score, negative changes indicate improvement (i.e. the score has decreased) and positive scores indicate a worsening of symptoms (i.e. scores have increased). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | Baseline and Day 60 | This measure is a 16 item self report questionnaire assessing symptoms of depression. For each item, scores range from 0 to 3 with higher scores indicating greater impairment. To score this measure: 1. Enter the highest score from questions 1-4 (sleep items): \_\_\_\_\_\_ 2. Enter score on item 5 \_\_\_\_ 3. Enter the highest score from questions 6-9 (appetite/weight): \_\_\_\_\_\_ 4. Enter score on item 10 \_\_\_\_ 5. Enter score on item 11 \_\_\_\_ 6. Enter score on item 12 \_\_\_\_ 7. Enter score on item 13 \_\_\_\_ 8. Enter score on item 14 \_\_\_\_ 9. Enter the highest score from questions 15-16 (psychomotor items): \_\_\_\_\_\_ Total score range 0-27: \_\_\_\_\_\_ When assessing changes in this measure over time, negative means indicate an improvement (i.e. the scores decreased over time) and positive means indicate worsening in functioning. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deplin/Deplin Participants will receive 15 mg/day of Deplin (6(S)-5-MTHF) for 8 weeks. | 19 |
| Placebo/Deplin Participants will receive placebo for the first 4 weeks, and then 15 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks. | 28 |
| Placebo/Placebo Both tablets of study medication will be placebo during both phases of the study. | 28 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo/Deplin | Placebo/Placebo | Deplin/Deplin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 28 Participants | 18 Participants | 74 Participants |
| Age, Continuous | 50.86 years STANDARD_DEVIATION 10.58 | 45.39 years STANDARD_DEVIATION 11.6 | 49.58 years STANDARD_DEVIATION 14.64 | 48.49 years STANDARD_DEVIATION 12.17 |
| Region of Enrollment United States | 28 participants | 28 participants | 19 participants | 75 participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 14 Participants | 53 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 42 | 48 / 54 |
| serious Total, serious adverse events | 0 / 42 | 0 / 54 |
Outcome results
Primary
The 17-item Hamilton Depression Scale (HAM-D-17)
The HAM-D-17 is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Items are scored on a scale of zero to four and higher scores indicate greater impairment. This scale is scored by summing the scores on each item and scores can range from 0-68. When assessing changes in HAMD score, negative changes indicate improvement (i.e. the score has decreased) and positive scores indicate a worsening of symptoms (i.e. scores have increased).
Time frame: Baseline and Day 60
Population: The phase II dataset of interest is limited to patients treated with placebo in phase I, completed phase I, did not experience a clinical response and entered phase II. Drug is compared to placebo in phase II for this subset alone. Some patients received Deplin in both phases of the study, but those patients are not included in these analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adjunct 6(S)-5-MTHF(Deplin) Phase 1 | The 17-item Hamilton Depression Scale (HAM-D-17) | -7.4 Scores on a scale | Standard Deviation 5.2 |
| Adjunct Placebo Phase 1 | The 17-item Hamilton Depression Scale (HAM-D-17) | -4.4 Scores on a scale | Standard Deviation 5.8 |
| Adjunct 6(S)-5-MTHF(Deplin) Phase 2 | The 17-item Hamilton Depression Scale (HAM-D-17) | -3.8 Scores on a scale | Standard Deviation 6.2 |
| Adjunct Placebo Phase 2 | The 17-item Hamilton Depression Scale (HAM-D-17) | -1.7 Scores on a scale | Standard Deviation 4.7 |
| Pooled Deplin | The 17-item Hamilton Depression Scale (HAM-D-17) | -5.58 Scores on a scale | Standard Deviation 5.7 |
| Pooled Placebo | The 17-item Hamilton Depression Scale (HAM-D-17) | -3.04 Scores on a scale | Standard Deviation 5.3 |
Comparison: Hypothesis 1: There will be a statistically significant difference between the two groups in the degree of improvement, as measured by the change in the 17-item Hamilton Depression Rating Scale (HAM-D-17) score from baseline to endpoint, using the sequential parallel comparison design \[51\]; with a greater degree of reduction in HAM-D-17 scores in the 6(S)-5-MTHF 15 mg qd group than in the placebo group, with the change on placebo being estimated from Trials 1 and 2.p-value: 0.05SPCD
Secondary
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
This measure is a 16 item self report questionnaire assessing symptoms of depression. For each item, scores range from 0 to 3 with higher scores indicating greater impairment. To score this measure: 1. Enter the highest score from questions 1-4 (sleep items): \_\_\_\_\_\_ 2. Enter score on item 5 \_\_\_\_ 3. Enter the highest score from questions 6-9 (appetite/weight): \_\_\_\_\_\_ 4. Enter score on item 10 \_\_\_\_ 5. Enter score on item 11 \_\_\_\_ 6. Enter score on item 12 \_\_\_\_ 7. Enter score on item 13 \_\_\_\_ 8. Enter score on item 14 \_\_\_\_ 9. Enter the highest score from questions 15-16 (psychomotor items): \_\_\_\_\_\_ Total score range 0-27: \_\_\_\_\_\_ When assessing changes in this measure over time, negative means indicate an improvement (i.e. the scores decreased over time) and positive means indicate worsening in functioning.
Time frame: Baseline and Day 60
Population: Data presented is mean score reduction for the QIDS. The dataset of interest is limited to patients treated with placebo in phase I, did not experience a clinical response and entered phase II. Drug is compared to placebo in phase II for this subset alone.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adjunct 6(S)-5-MTHF(Deplin) Phase 1 | The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | -8.1 Scores on a scale | Standard Deviation 5.3 |
| Adjunct Placebo Phase 1 | The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | -5.7 Scores on a scale | Standard Deviation 5.6 |
| Adjunct 6(S)-5-MTHF(Deplin) Phase 2 | The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | -1.3 Scores on a scale | Standard Deviation 4.9 |
| Adjunct Placebo Phase 2 | The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | 0.5 Scores on a scale | Standard Deviation 5 |