Trial Outcomes & Findings for Predictors of Antidepressant Response (NCT NCT02178696)
NCT ID: NCT02178696
Last Updated: 2017-12-05
Results Overview
Binding Potential = Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with positron emission tomography. Whole brain changes in mu-opioid receptors binding potential during PET from the Inactive to the Active placebo condition. Positive numbers presented here represent reductions in binding potential from the inactive to the active condition.
COMPLETED
PHASE4
44 participants
(90 minute PET scans) assessed at Weeks 1 and 2
2017-12-05
Participant Flow
4 consented volunteers dropped because of exclusion criteria
Of 44 participants consented, 4 were not assigned to participate due to screen failures.
Participant milestones
| Measure |
Known Placebo First
This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
Placebo, identified as placebo to participants: White tablets
Celexa or other antidepressant as clinically indicated: Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg
Placebo, identifed to participants as "Active medication": Blue Capsule
|
"Active" (Blinded) Placebo First Group
This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
Placebo, identified as placebo to participants: White tablets
Celexa or other antidepressant as clinically indicated: Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg
Placebo, identifed to participants as "Active medication": Blue Capsule
|
|---|---|---|
|
First Assignment and Washout
STARTED
|
20
|
20
|
|
First Assignment and Washout
COMPLETED
|
20
|
20
|
|
First Assignment and Washout
NOT COMPLETED
|
0
|
0
|
|
Second Assignment After Crossover
STARTED
|
20
|
20
|
|
Second Assignment After Crossover
COMPLETED
|
20
|
20
|
|
Second Assignment After Crossover
NOT COMPLETED
|
0
|
0
|
|
Open-label Antidepressant
STARTED
|
20
|
20
|
|
Open-label Antidepressant
COMPLETED
|
14
|
13
|
|
Open-label Antidepressant
NOT COMPLETED
|
6
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Predictors of Antidepressant Response
Baseline characteristics by cohort
| Measure |
Total Study Population
n=40 Participants
|
|---|---|
|
Age, Customized
19 to 59 years
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: (90 minute PET scans) assessed at Weeks 1 and 2Population: Data in four subjects was missing due to failure in the synthesis of the radio tracer for at least one of the two scans.
Binding Potential = Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with positron emission tomography. Whole brain changes in mu-opioid receptors binding potential during PET from the Inactive to the Active placebo condition. Positive numbers presented here represent reductions in binding potential from the inactive to the active condition.
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=36 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
|
|---|---|---|
|
Changes in Mu-opioid Binding Potential During PET
|
0.12 Binding potential ratio
Standard Deviation 0.32
|
—
|
PRIMARY outcome
Timeframe: (90 minute fMRI scans) assessed at Weeks 1 and 2Population: Data was missing in 11 subjects due to movement artifacts, or incidental findings that made the data not usable.
% BOLD signal changes in the nucleus accumbens from the Inactive to the Active Placebo condition.
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=29 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
|
|---|---|---|
|
Changes in BOLD Response During Reward fMRI Task (Monetary Incentive Delay, MID)
|
0.04 % BOLD changes from Inactive to Active
Standard Deviation 1.13
|
—
|
SECONDARY outcome
Timeframe: (90 minute PET scan) assessed at Weeks 1 and 2Population: Data was only collected in 26 subjects as proposed.
Binding Potential= Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with PET. Striatal changes in D2/3 receptor binding potential during PET from the Inactive to the Active condition. Positive numbers presented here represented reductions in binding potential from the inactive to the active condition.
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=26 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
|
|---|---|---|
|
Changes in Dopamine (D 2/3) Binding Potential During PET.
|
0.08 Binding potential ratio
Standard Deviation 0.15
|
—
|
SECONDARY outcome
Timeframe: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)Population: Changes in QIDS-16SR from screening active/inactive placebo condition to the post scan active/inactive placebo condition. Approximately 1-2 weeks between the two conditions.
This scale is a self-report measure of depression with 16 items. Questions in the QIDS - SR-116 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). Severity of depression can be judged based on the total score: 1-5= No depression; 6-10= Mild depression; 11-15= Moderate depression; 16-20= Severe depression; 21-27= Very severe depression. The PHQ-9 and QIDS were used to assess changes in mood during the placebo intervention (first 2 weeks), and therefore results are described as changes from the inactive to the active condition.
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=40 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
n=40 Participants
|
|---|---|---|
|
Changes From Baseline in Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) Score
|
1.7 Units on a scale
Standard Error 3.3
|
-0.5 Units on a scale
Standard Error 3.2
|
SECONDARY outcome
Timeframe: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)Population: Changes in PHQ-9 score from the beginning of the active/inactive placebo and the end of active/inactive PET scan. Approximately 1-2 weeks between the two conditions.
The Patient Health Questionnaire-9, is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression, based on participant answers. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression, respectively. The minimum possible score is 0 and the maximum possible score is 27. The PHQ-9 and QIDS were used to assess changes in mood during the placebo intervention (first 2 weeks), and therefore results are described as changes from the inactive to the active condition.
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=40 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
n=40 Participants
|
|---|---|---|
|
Changes From Baseline in PHQ-9 Depression Scores.
|
1.6 Units on a scale
Standard Deviation 3.6
|
0.96 Units on a scale
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: Screening, week 0, week 2, week 4, week 8 and week 10The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). For the 17-item version, scores can range from 0 to 54, with 0 meaning no depression, and 54, severe depression. The Hamilton Depression Rating Scale was used to assess symptoms during the open label antidepressant treatment phase, so results are described as mean scores at each bi-weekly visit.
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=40 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
|
|---|---|---|
|
Hamilton Depression Rating Scale Scores
week 0
|
17.2 Units on a scale
Standard Deviation 6.5
|
—
|
|
Hamilton Depression Rating Scale Scores
Screening
|
21 Units on a scale
Standard Deviation 4.4
|
—
|
|
Hamilton Depression Rating Scale Scores
week 2
|
13.3 Units on a scale
Standard Deviation 7.18
|
—
|
|
Hamilton Depression Rating Scale Scores
Week 4
|
11 Units on a scale
Standard Deviation 7.73
|
—
|
|
Hamilton Depression Rating Scale Scores
week 8
|
8.65 Units on a scale
Standard Deviation 6.78
|
—
|
|
Hamilton Depression Rating Scale Scores
week 10
|
5.3 Units on a scale
Standard Deviation 3.75
|
—
|
SECONDARY outcome
Timeframe: Screening, week 0, week 2, week 4, week 8 and week 10Designed in 1979 by researchers as an adjunct to the Hamilton Rating Scale for Depression (HAMD) which would be more sensitive to the changes brought on by antidepressants and other forms of treatment than the Hamilton Scale. MADRS was used to assess symptoms during the open label antidepressant treatment phase, so results are described as mean scores at each bi-weekly visit. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 where 0 is no depression and 60 is most extreme depression. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts Usual cutoff points are: 0 to 6 - normal\[5\] /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression
Outcome measures
| Measure |
Changes in Mu-opioid Binding (Inactive -Active Placebo)
n=40 Participants
Average regional changes in mu-opioid binding potential from the Inactive to the Active Placebo Condition.
|
Inactive Placebo
|
|---|---|---|
|
Montgomery-Asberg Depression Rating Scale
Baseline
|
27 Units on a scale
Standard Deviation 6.6
|
—
|
|
Montgomery-Asberg Depression Rating Scale
week 0
|
22 Units on a scale
Standard Deviation 8.4
|
—
|
|
Montgomery-Asberg Depression Rating Scale
week 2
|
15 Units on a scale
Standard Deviation 7
|
—
|
|
Montgomery-Asberg Depression Rating Scale
week 4
|
13 Units on a scale
Standard Deviation 10
|
—
|
|
Montgomery-Asberg Depression Rating Scale
week 8
|
11 Units on a scale
Standard Deviation 9.7
|
—
|
|
Montgomery-Asberg Depression Rating Scale
week 10
|
7.7 Units on a scale
Standard Deviation 5.36
|
—
|
Adverse Events
Placebo (Unknown)
Known Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place