The Serotonin Transporter Availability for Prognosing Major Depressive Disorder (MDD) Treatment and Detecting MDD

Phase 2

Completed

• Conditions: Major Depressive Disorder
• Interventions: Drug: Sertraline HCl; Other: I-123-ADAM SPECT

• Registration Number: NCT02473783
• Lead Sponsor: Tri-Service General Hospital

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.

Study Timeline

• Study Start: 2011-10
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Study First Submitted: 2015-06-11
• Study First Submitted QC: 2015-06-16
• Study First Posted: 2015-06-17
• Results First Submitted: 2017-08-15
• Results First Submitted QC: 2017-11-22
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-20
• Results First Posted: 2017-12-21
• Last Update Posted: 2018-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Group	Sertraline HCl	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.
Treatment Group	I-123-ADAM SPECT	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.