Major Depressive Disorder
Conditions
Brief summary
Objectives: 1. To evaluate the relationship between improvement of Hamilton Depression Rating Scale (HAMD) score and basal SERT availability (binding potential) for the prognosis of MDD subjects being treated with Sertraline HCl 2. To evaluate the SERT availability by means of I-123-ADAM SPECT imaging study for assisting in detecting MDD 3. To evaluate the relationship between basal HAMD score and basal SERT availability for MDD subjects 4. To evaluate the relationship between basal HAMD somatic subscale score and basal SERT availability for MDD subjects 5. To evaluate the relationship between change of SERT availability and change of HAMD score for MDD patients being treated with Sertraline HCl
Detailed description
Background: Serotonin transporter (SERT) plays an important role in the pathophysiology of psychiatric disorders such as anxiety and depression and is the primary target of the selective serotonin reuptake inhibitors (SSRIs) which are posited to exert their effect in treating psychiatric disorders aforementioned by this mechanism. I-123-ADAM is a selective radioligand for imaging SERT using SPECT. Research showed that it displayed an extremely high binding affinity to SERT sites. Previous literature also suggested the potential role of I-123-ADAM SPECT as useful in understanding how serotonin system affected depression. This study aims to evaluate the SERT availability by means of I-123-ADAM SPECT imaging study in drug-free subjects for prognosing MDD treatment and assisting in detecting MDD. Methods: We enrolled patients who had major depressive disorder but was free from prior antidepressant medication for at least 5 times of elimination half-lives and healthy controls. The patients with major depressive disorder (N=20) received I-123-ADAM SPECT before and after the pharmacological intervention with Sertraline HCl for a treatment period of six weeks. All healthy subjects (N=17) had only basal I-123-ADAM SPECT. The relationship between improvement of depressive symptoms and basal SERT availability for the prognosis of MDD subjects being treated with Sertraline HCl will be analyzed. In addition, the association between the efficacy of treatment with Sertraline HCl and the change of SERT availability will also be investigated. The control group were selected in order to distinguish the difference of basal SERT binding potential of I-123-ADAM between healthy and MDD subjects.
Interventions
DRUGSertraline HCl
The regimen of Sertraline HCl will be administered with starting dose from minimum 25 mg/day for 1 week and maintenance dose of at least 50 mg/day up to 200 mg/day for the rest of 5 weeks.
OTHERI-123-ADAM SPECT
The subjects underwent the SPECT scan after I-123-ADAM (185 MBq, 5mCi) IV injection.
Sponsors
National Atomic Research Institute, Taiwan
Tri-Service General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
\- For MDD subjects 1. Subject meets the DSM-IV criteria for MDD 2. Subject has a minimum score of 18 on the 17-item HAMD total score 3. Subject has a minimum score of 2 on item 1, depressed mood, of HAMD 4. Subject is free from prior antidepressant medication for at least 5 times of elimination half-lives For healthy subjects 1. Subject without past or current neuropsychiatric illnesses based on a clinical interview including Mini-International Neuropsychiatric Interview (M.I.N.I.) and a physical examination 2. Subject without exposure to psychotropic medication or other substances known to affect the brain serotonin system within 1 year prior to entering the study
Exclusion criteria
1. Subject with history of any co-morbid neuropsychiatric disease 2. Subject with history of treatment resistant to at least two full doses and courses of antidepressant medication 3. Subject with history of alcohol or substance dependence or abuse 4. Subject with allergic history to the investigational products 5. Subject with severe cardiovascular disease or cerebrovascular disease which is judged by investigators for safety concerns as inappropriate for this study 6. Subject with malignancy within past 5 years 7. Subject with any diseases judged by investigators as inappropriate for this study 8. Female subject being pregnant, nursing, or lactating 9. Female subject of childbearing potential not using a medically acceptable form of birth control 10. Subject is unable to undergo MRI scan to confirm the absence of organic lesion in the brain and to co-register with SPECT images for the delineation of brain anatomical locations 11. Subject participated in any investigational drug trial within 4 weeks before entering this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The SERT Binding Potential (BP) --(Only the Treatment Group Was Assessed) | 6 weeks (The Healthy control Group only had the scanning at baseline) | Binding potential (BP) is a ratio of specific to non-displaceable binding (BP = (target region - cerebellum) / cerebellum) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HAM-D) Total Scores | 6 weeks | The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. It contains 17 items to be rated. Each item on the questionnaire is scored on a 3 or 5 point scale. The range of the total score (summed) is from 0 to 52.The higher total score suggests the more severe depression. |
| Safety Assessments - the Tolerability of Injection of I-123-ADAM Solution | assessed at -5~0 days and 6 weeks ±5 days, -5~0 days reported (I-123-ADAM SPECT scan) | Pain Scores as measured by the Visual Analog Scale (0-10) for the tolerability of injection of I-123-ADAM solution. Higher values represent a worse outcome. |
Participant flow
Recruitment details
The recruitment period was from Oct-07-2011 to Nov-28-2012. The recruitment site was a psychiatric outpatient in a medical center.
Pre-assignment details
The treatment group: No significant events in the study that occur after participant enrollment. The healthy control group: No significant events in the study that occur after participant enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group The subjects with major depressive disorder who are screened into this study were scheduled for T1-weighted MRI (MRI examination results within 6 months before study are acceptable) prior to the visit of SPECT scans to confirm the absence of organic lesion in the brain and to co-register with SPECT images for the delineation of brain anatomical locations. After the screening visit, eligible subjects received I-123-ADAM SPECT before and after the pharmacological intervention with Sertraline HCl for a treatment period of six weeks. The subjects were observed until no clinically significant adverse events at the drug administration visits before being dismissed.
Sertraline HCl: The regimen of Sertraline HCl will be administered with starting dose from minimum 25 mg/day for 1 week and maintenance dose of at least 50 mg/day up to 200 mg/day for the rest of 5 weeks.
I-123-ADAM SPECT: The subjects underwent the SPECT scan after I-123-ADAM (185 MBq, 5mCi) IV injection. | 20 |
| Healthy Control Group All healthy subjects (N=17) had only basal I-123-ADAM SPECT scanning. | 17 |
| Total | 37 |
Baseline characteristics
| Characteristic | Treatment Group | Healthy Control Group | Total |
|---|---|---|---|
| Age, Continuous | 38.15 years STANDARD_DEVIATION 12.35 | 36.35 years STANDARD_DEVIATION 12.72 | 37.32 years STANDARD_DEVIATION 12.38 |
| Hamilton Depression Rating Scale (HAMD) total score | 22.90 units on a scale | NA units on a scale | 22.90 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 17 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 20 Participants | 17 Participants | 37 Participants |
| serotonin transporter (SERT) binding potential over right basal ganglion | 0.52 ratio STANDARD_DEVIATION 0.28 | 0.94 ratio STANDARD_DEVIATION 1.32 | 0.68 ratio STANDARD_DEVIATION 0.86 |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 20 | 0 / 17 |
| serious Total, serious adverse events | 0 / 20 | 0 / 17 |
Outcome results
Primary
The SERT Binding Potential (BP) --(Only the Treatment Group Was Assessed)
Binding potential (BP) is a ratio of specific to non-displaceable binding (BP = (target region - cerebellum) / cerebellum)
Time frame: 6 weeks (The Healthy control Group only had the scanning at baseline)
Population: All the participants in the Intention -to-treatment group completed the study. Since the healthy control group did not receive the pharmacological intervention, they underwent only the baseline assessments but not the follow-up ones. Therefore, we reported only the outcome measures of the treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | The SERT Binding Potential (BP) --(Only the Treatment Group Was Assessed) | 0.34 a ratio of target region to background | Standard Deviation 0.26 |
Secondary
Hamilton Depression Rating Scale (HAM-D) Total Scores
The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. It contains 17 items to be rated. Each item on the questionnaire is scored on a 3 or 5 point scale. The range of the total score (summed) is from 0 to 52.The higher total score suggests the more severe depression.
Time frame: 6 weeks
Population: All the participants in the Intention -to-treatment group completed the study. Since the healthy control group did not receive the pharmacological intervention, they underwent only the baseline assessments but not the follow-up ones. Therefore, we reported only the outcome measures of the treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Hamilton Depression Rating Scale (HAM-D) Total Scores | 5.25 units on a scale | Standard Deviation 4.01 |
Secondary
Safety Assessments - the Tolerability of Injection of I-123-ADAM Solution
Pain Scores as measured by the Visual Analog Scale (0-10) for the tolerability of injection of I-123-ADAM solution. Higher values represent a worse outcome.
Time frame: assessed at -5~0 days and 6 weeks ±5 days, -5~0 days reported (I-123-ADAM SPECT scan)
Population: All the participants in the Intention -to-treatment group completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Safety Assessments - the Tolerability of Injection of I-123-ADAM Solution | 1.52 units on a scale | Standard Deviation 2.76 |
| Healthy Control Group | Safety Assessments - the Tolerability of Injection of I-123-ADAM Solution | 0.88 units on a scale | Standard Deviation 1.96 |