Trial Outcomes & Findings for Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression (NCT NCT00953745)
NCT ID: NCT00953745
Last Updated: 2018-04-19
Results Overview
A ratio of the image derived radioactivity concentration and the whole body concentration of the injected radioactivity specifically in a cluster within the right medial caudate (see data below).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
43 participants
Primary outcome timeframe
Week 10 and Week 16 (6 weeks of combined therapy)
Results posted on
2018-04-19
Participant Flow
Participant milestones
| Measure |
Depressed Participants
Subjects with treatment-resistant depression (TRD) will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks.
Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks.
|
Control Participants
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used to compare the pre-ARP and post-ARP treatment brain images to draw conclusions about the pre-treatment state (depression) and post-treatment state (depression responders).
|
|---|---|---|
|
Phase 1: 8 Weeks Escitalopram + Placebo
STARTED
|
37
|
6
|
|
Phase 1: 8 Weeks Escitalopram + Placebo
COMPLETED
|
24
|
6
|
|
Phase 1: 8 Weeks Escitalopram + Placebo
NOT COMPLETED
|
13
|
0
|
|
Phase 2: 2 Weeks Escitalopram + Placebo
STARTED
|
18
|
0
|
|
Phase 2: 2 Weeks Escitalopram + Placebo
COMPLETED
|
17
|
0
|
|
Phase 2: 2 Weeks Escitalopram + Placebo
NOT COMPLETED
|
1
|
0
|
|
ARP Phase: 6 Weeks Escitalopram + ARP
STARTED
|
17
|
0
|
|
ARP Phase: 6 Weeks Escitalopram + ARP
COMPLETED
|
17
|
0
|
|
ARP Phase: 6 Weeks Escitalopram + ARP
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Depressed Participants
Subjects with treatment-resistant depression (TRD) will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks.
Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks.
|
Control Participants
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used to compare the pre-ARP and post-ARP treatment brain images to draw conclusions about the pre-treatment state (depression) and post-treatment state (depression responders).
|
|---|---|---|
|
Phase 1: 8 Weeks Escitalopram + Placebo
Pregnancy
|
1
|
0
|
|
Phase 1: 8 Weeks Escitalopram + Placebo
Withdrawal by Subject
|
2
|
0
|
|
Phase 1: 8 Weeks Escitalopram + Placebo
Lost to Follow-up
|
3
|
0
|
|
Phase 1: 8 Weeks Escitalopram + Placebo
Adverse Event
|
1
|
0
|
|
Phase 1: 8 Weeks Escitalopram + Placebo
Screen failures
|
6
|
0
|
|
Phase 2: 2 Weeks Escitalopram + Placebo
Pregnancy
|
1
|
0
|
Baseline Characteristics
Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression
Baseline characteristics by cohort
| Measure |
Depressed Participants
n=37 Participants
Subjects with treatment-resistant depression (TRD) will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks.
Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks.
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
Control Participants
n=6 Participants
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used to compare the pre-ARP and post-ARP treatment brain images to draw conclusions about the pre-treatment state (depression) and post-treatment state (depression responders).
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.69 years
n=93 Participants
|
45.67 years
n=4 Participants
|
42.27 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=93 Participants
|
6 participants
n=4 Participants
|
43 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Week 10 and Week 16 (6 weeks of combined therapy)Population: The outcome purpose was to examine mechanism of action of aripiprazole in responders versus nonresponders. Control subjects were age and gender matched to study subjects and underwent one set of scans (fMRI, raclopride and FOPA PET scans) for use as a comparison group for quality control on a non-depressed population and not for data analysis.
A ratio of the image derived radioactivity concentration and the whole body concentration of the injected radioactivity specifically in a cluster within the right medial caudate (see data below).
Outcome measures
| Measure |
ARP Responders
n=11 Participants
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP. ARP Responders will have had a 50% or greater drop in their MADRS scores from baseline.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
ARP Non-Responders
n=3 Participants
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP. ARP Responders will have had a 50% or greater drop in their MADRS scores from baseline.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
|---|---|---|
|
Fluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders
Week 10
|
1.297 FDOPA ratio in the right medial caudate
Standard Deviation 0.176
|
1.363 FDOPA ratio in the right medial caudate
Standard Deviation 0.180
|
|
Fluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders
Week 16
|
1.333 FDOPA ratio in the right medial caudate
Standard Deviation 0.175
|
1.350 FDOPA ratio in the right medial caudate
Standard Deviation 0.252
|
SECONDARY outcome
Timeframe: Week 10 and Week 16 (6 weeks of combined therapy)Population: MADRS score comparison between ARP responders and nonresponders.
Montgomery-Åsberg Depression Rating (MADRS) Scale scores compared between the 6 week Aripiprazole augmentation groups (responds vs. non-responders). Total range of the MADRS is 0 to 60, with a score of greater than 34 indicating severe depression, 20-34 indicating moderate depression, 7-19 mild depression, and 0-6 normal or absent of symptoms.
Outcome measures
| Measure |
ARP Responders
n=11 Participants
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP. ARP Responders will have had a 50% or greater drop in their MADRS scores from baseline.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
ARP Non-Responders
n=3 Participants
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP. ARP Responders will have had a 50% or greater drop in their MADRS scores from baseline.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
|---|---|---|
|
Depression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders.
Week 16
|
6.5 score on the MADRS scale
Standard Deviation 3.0
|
25.3 score on the MADRS scale
Standard Deviation 5.5
|
|
Depression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders.
Week 10
|
27.9 score on the MADRS scale
Standard Deviation 5.6
|
31.7 score on the MADRS scale
Standard Deviation 12.7
|
Adverse Events
Depressed Participants
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Control Participants
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Depressed Participants
n=37 participants at risk
Subjects with treatment-resistant depression (TRD) will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks.
Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks.
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
Control Participants
n=6 participants at risk
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used to compare the pre-ARP and post-ARP treatment brain images to draw conclusions about the pre-treatment state (depression) and post-treatment state (depression responders).
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Birth of a baby (deception by subject)
|
3.7%
1/27 • Number of events 1
|
0.00%
0/6
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
3.7%
1/27 • Number of events 1
|
0.00%
0/6
|
Other adverse events
| Measure |
Depressed Participants
n=37 participants at risk
Subjects with treatment-resistant depression (TRD) will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks.
Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks.
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
|
Control Participants
n=6 participants at risk
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used to compare the pre-ARP and post-ARP treatment brain images to draw conclusions about the pre-treatment state (depression) and post-treatment state (depression responders).
|
|---|---|---|
|
Nervous system disorders
Increased fatigue
|
29.7%
11/37
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
18.9%
7/37
|
0.00%
0/6
|
|
Nervous system disorders
Akathisia
|
10.8%
4/37
|
0.00%
0/6
|
|
Nervous system disorders
Insomnia
|
5.4%
2/37
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
13.5%
5/37
|
0.00%
0/6
|
|
Nervous system disorders
Increased sweating
|
5.4%
2/37
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
5.4%
2/37
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Lightheadedness
|
5.4%
2/37
|
0.00%
0/6
|
|
Nervous system disorders
Restlessness
|
10.8%
4/37
|
0.00%
0/6
|
|
Nervous system disorders
Decreased libido
|
8.1%
3/37
|
0.00%
0/6
|
|
Nervous system disorders
Vivid dreaming
|
10.8%
4/37
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Dizziness
|
8.1%
3/37
|
0.00%
0/6
|
Additional Information
Dr. Charles R. Conway, MD
Washington University School of Medicine
Phone: 314-362-7566
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place