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

• Sponsor: Tri-Service General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02473783
• Collaborator: Institute of Nuclear Energy Research, Taiwan (Other)
• Enrollment: 37
• Arm: 1
• Duration (Months): 13

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Sertraline HCl; Other: I-123-ADAM SPECT	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An I-123-ADAM SPECT Imaging Study to Evaluate the Serotonin Transporter (SERT) Availability for Prognosing Major Depressive Disorder (MDD) Treatment and Assisting in Detecting MDD
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.; Other Names: Zoloft ; Other: I-123-ADAM SPECT; The subjects underwent the SPECT scan after I-123-ADAM (185 MBq, 5mCi) IV injection.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Tri-Service General Hospital
• Institute of Nuclear Energy Research, Taiwan

Investigators

• Principal Investigator: Chin-Bin Yeh, M.D., Ph.D., Tri-Service General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chin-Bin Yeh, MD, PhD, Director of Department of Psychiatry, Tri-Service General Hospital
• ClinicalTrials.gov Identifier: NCT02473783
• Other Study ID Numbers: INEI-1A20090409
• First Posted: Jun 17, 2015
• Last Update Posted: Jan 19, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Sertraline

Study Results

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 Detail	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.

Arm/Group Title	Treatment Group	Healthy Control Group
Arm/Group Description	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.	All healthy subjects had only basal I-123-ADAM SPECT scanning
Period Title: Overall Study
STARTED	20	17
COMPLETED	20	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Treatment Group	Healthy Control Group	Total
Arm/Group Description	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.	All healthy subjects (N=17) had only basal I-123-ADAM SPECT scanning.	Total of all reporting groups
Overall Participants	20	17	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.15 (12.35)	36.35 (12.72)	37.32 (12.38)
Sex: Female, Male (Count of Participants)
Female	12 60%	10 58.8%	22 59.5%
Male	8 40%	7 41.2%	15 40.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	20 100%	17 100%	37 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Taiwan	20 100%	17 100%	37 100%
Hamilton Depression Rating Scale (HAMD) total score (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	22.90	NA	22.90
serotonin transporter (SERT) binding potential over right basal ganglion (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	0.52 (0.28)	0.94 (1.32)	0.68 (0.86)

Outcome Measures

1. Primary Outcome

Title	The SERT Binding Potential (BP) --(Only the Treatment Group Was Assessed)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Treatment Group
Arm/Group Description	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.
Measure Participants	20
Mean (Standard Deviation) [a ratio of target region to background]	0.34 (0.26)

2. Secondary Outcome

Title	Hamilton Depression Rating Scale (HAM-D) Total Scores
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Treatment Group
Arm/Group Description	The subjects with major depressive disorder were assessed with Hamilton Depression Rating Scale (HAM-D) before and after 6 weeks of Sertraline HCl treatment.
Measure Participants	20
Mean (Standard Deviation) [units on a scale]	5.25 (4.01)

3. Secondary Outcome

Title	Safety Assessments - the Tolerability of Injection of I-123-ADAM Solution
Description	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)

Outcome Measure Data

Analysis Population Description

All the participants in the Intention -to-treatment group completed the study.

Arm/Group Title	Treatment Group	Healthy Control Group
Arm/Group Description	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.	All healthy subjects had only basal I-123-ADAM SPECT scanning.
Measure Participants	20	17
Mean (Standard Deviation) [units on a scale]	1.52 (2.76)	0.88 (1.96)

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	The healthy control group did not receive the pharmacological intervention, they underwent only the baseline assessments and were only monitored for adverse events at baseline.
Arm/Group Title	Treatment Group		Healthy Control Group
Arm/Group Description	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.		All healthy subjects had only basal I-123-ADAM SPECT scanning.
All Cause Mortality
	Treatment Group		Healthy Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment Group		Healthy Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Group		Healthy Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/17 (0%)
Eye disorders
conjunctivitis	1/20 (5%)	1	0/17 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.