Trial Outcomes & Findings for Pharmacogenomics for Antidepressant Guidance and Education (NCT NCT01555021)
NCT ID: NCT01555021
Last Updated: 2018-11-05
Results Overview
To determine the efficacy of assay-guided treatment (AGT) versus treatment-as-usual (TAU), in terms of depression severity as measured by change in the Quick Inventory of Depressive Symptoms (QIDS-SR 16), adjusted for baseline severity, upon discharge, and at 1, 3, and 6 months post discharge from inpatient treatment. The QUIDS-SR 16 is a self rating 16 item multiple-choice questionnaire that measure severity of depression over the past week. The range on the QIDS-SR IS 0-27, with 0-5 indicating no depression; 6-10, mild depression; 11-15; moderate depression; 16-20 severe depression; and greater than or equal to 21, very severe depression.
Recruitment status
TERMINATED
Target enrollment
4 participants
Primary outcome timeframe
Measured: Baseline (within 72 hours of admission), once weekly (+/- 24 hours), discharge (7-10 days after admission +/- 24 hours), and 1, 3, 6 months after discharge (+/- 4 weeks)
Results posted on
2018-11-05
Participant Flow
Although clinicians were randomized to either receive or not receive the AGT results, they were not considered enrolled. Only the patients were enrolled in the study. Also, each participating clinician covered only one subject.
Participant milestones
| Measure |
Treatment as Usual
Subjects will provide blood samples prior to treatment, but will have their blood stored for later analysis.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will provide a saliva samples for GWAS analyses at a later date. However, the GWAS analyses were not performed due to the early termination of the study.
|
Assay Guided Treatment
This test is used to guide clinicians in their recommendation antidepressant drugs based on CYP 450 gene activity for 1A2, 2C9, 2C19, 2D6, and 3A/4.
Subjects will be asked to provide blood samples. For subjects in the Assay-Guided Treatment group, their blood will be genotyped. Their psychiatrists will be given the results of the tests and then they will decide which antidepressants to use.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide saliva samples for GWAS analysis at a later date; however, GWAS analysis was not performed due to early termination of the study.
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
2
|
|
Overall Study
COMPLETED
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Treatment as Usual
Subjects will provide blood samples prior to treatment, but will have their blood stored for later analysis.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will provide a saliva samples for GWAS analyses at a later date. However, the GWAS analyses were not performed due to the early termination of the study.
|
Assay Guided Treatment
This test is used to guide clinicians in their recommendation antidepressant drugs based on CYP 450 gene activity for 1A2, 2C9, 2C19, 2D6, and 3A/4.
Subjects will be asked to provide blood samples. For subjects in the Assay-Guided Treatment group, their blood will be genotyped. Their psychiatrists will be given the results of the tests and then they will decide which antidepressants to use.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide saliva samples for GWAS analysis at a later date; however, GWAS analysis was not performed due to early termination of the study.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
Baseline Characteristics
Pharmacogenomics for Antidepressant Guidance and Education
Baseline characteristics by cohort
| Measure |
Treatment as Usual
n=2 Participants
Subjects in the Treatment as Usual group will proceed with treatment as usual, but have their blood samples for genotyping stored for future analysis.
Patients will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide saliva samples for GWAS analysis at a later date (note: GWAS analysis and genotyping for the Treatment as Usual group was not performed due to early termination of the study)
Patients will be asked to participate in 3 follow-up phone calls to measure their mood.
|
Assay Guided Treatment
n=2 Participants
This group will receive a genotyping test to determine the specific levels of gene activity. This test was used to guide clinicians decision making for which antidepressants to prescribe and/or at what doses.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide saliva samples for GWAS analysis at a later date (note; GWAS analysis was not performed in the AGT group due to early termination of the study.
Subjects will be asked to participate in 3 follow-up phone calls to measure their mood.
|
Total
n=4 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
59 years
n=5 Participants
|
43.5 years
n=7 Participants
|
51.25 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Measured: Baseline (within 72 hours of admission), once weekly (+/- 24 hours), discharge (7-10 days after admission +/- 24 hours), and 1, 3, 6 months after discharge (+/- 4 weeks)Population: Quick Inventory of Depression symptom-16 (QIDS-SR 16) Baseline. Data was not collected for all time points for all participants.
To determine the efficacy of assay-guided treatment (AGT) versus treatment-as-usual (TAU), in terms of depression severity as measured by change in the Quick Inventory of Depressive Symptoms (QIDS-SR 16), adjusted for baseline severity, upon discharge, and at 1, 3, and 6 months post discharge from inpatient treatment. The QUIDS-SR 16 is a self rating 16 item multiple-choice questionnaire that measure severity of depression over the past week. The range on the QIDS-SR IS 0-27, with 0-5 indicating no depression; 6-10, mild depression; 11-15; moderate depression; 16-20 severe depression; and greater than or equal to 21, very severe depression.
Outcome measures
| Measure |
Treatment as Usual
n=2 Participants
Subjects will be asked to provide blood samples for CYP 450 genotyping; however, the genotyping analysis will occur at a later date.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: genotyping analysis and GWAS analysis was not performed due to early termination of the study)
|
Assay Guided Treatment
n=2 Participants
This test is used to guide clinicians in their recommendations for antidepressant drugs based on CYP 450 gene activity for 1A2, 2C9, 2C19, 2D6, and 3A/4.
Subjects will be asked to provide a blood samples for CYP 450 genotyping. Subjects in the Assay-Guided Treatment group, will have their blood samples genotyped immediately. Their psychiatrists will be given the results of the tests within 3 to 5 days and then they will decide which antidepressants to use.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: GWAS analysis was not performed due to early termination of the study)
|
|---|---|---|
|
Change in Quick Inventory of Depressive Symptoms-Self Rating (SR) 16 Item
QIDS-SR 16 Baseline
|
18 Score on QIDS-SR
Interval 17.0 to 19.0
|
22.5 Score on QIDS-SR
Interval 18.0 to 27.0
|
|
Change in Quick Inventory of Depressive Symptoms-Self Rating (SR) 16 Item
QIDS 16 Discharge
|
7.5 Score on QIDS-SR
Interval 6.0 to 9.0
|
—
|
|
Change in Quick Inventory of Depressive Symptoms-Self Rating (SR) 16 Item
QIDS 16 at 1 month
|
6 Score on QIDS-SR
Interval 6.0 to 6.0
|
—
|
|
Change in Quick Inventory of Depressive Symptoms-Self Rating (SR) 16 Item
QIDS 16 at 3 months
|
4 Score on QIDS-SR
Interval 4.0 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Measured: +/- 24 hours of baseline assessments and +/- 24 hours of receiving assay resultsPopulation: 2 of 4 clinicians received AGT results for antidepressant decision making. One of two clinicians randomized to receive AGT results reported that his choice of antidepressant was definitely influenced by AGT results; the other clinician randomized to receive AGT results did not receive the AGT information within the defined time limit.
Clinicians randomized to receive AGT results were asked to report whether the AGT results impacted their decision making with regards to their choice of antidepressant and/or dosing of the antidepressant.
Outcome measures
| Measure |
Treatment as Usual
Subjects will be asked to provide blood samples for CYP 450 genotyping; however, the genotyping analysis will occur at a later date.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: genotyping analysis and GWAS analysis was not performed due to early termination of the study)
|
Assay Guided Treatment
n=2 Participants
This test is used to guide clinicians in their recommendations for antidepressant drugs based on CYP 450 gene activity for 1A2, 2C9, 2C19, 2D6, and 3A/4.
Subjects will be asked to provide a blood samples for CYP 450 genotyping. Subjects in the Assay-Guided Treatment group, will have their blood samples genotyped immediately. Their psychiatrists will be given the results of the tests within 3 to 5 days and then they will decide which antidepressants to use.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: GWAS analysis was not performed due to early termination of the study)
|
|---|---|---|
|
Clinician's Report That AGT Modified His/Her Decision Regarding Which Antidepressant to Prescribe.
AGT beneficial in decision making
|
—
|
1 participants
|
|
Clinician's Report That AGT Modified His/Her Decision Regarding Which Antidepressant to Prescribe.
AGT not beneficial in decision making
|
—
|
0 participants
|
SECONDARY outcome
Timeframe: To determine the impact on adherence of AGT versus TAU at 7-10 days after admissionPopulation: Number of subjects adherent to antidepressant medications
To determine the impact on adherence of AGT versus TAU at 7-10 days after admission
Outcome measures
| Measure |
Treatment as Usual
n=2 Participants
Subjects will be asked to provide blood samples for CYP 450 genotyping; however, the genotyping analysis will occur at a later date.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: genotyping analysis and GWAS analysis was not performed due to early termination of the study)
|
Assay Guided Treatment
n=2 Participants
This test is used to guide clinicians in their recommendations for antidepressant drugs based on CYP 450 gene activity for 1A2, 2C9, 2C19, 2D6, and 3A/4.
Subjects will be asked to provide a blood samples for CYP 450 genotyping. Subjects in the Assay-Guided Treatment group, will have their blood samples genotyped immediately. Their psychiatrists will be given the results of the tests within 3 to 5 days and then they will decide which antidepressants to use.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: GWAS analysis was not performed due to early termination of the study)
|
|---|---|---|
|
Treatment Adherence
Number adherent at discharge
|
2 Participants
|
2 Participants
|
|
Treatment Adherence
Number adherent at 1 month
|
1 Participants
|
—
|
|
Treatment Adherence
Number adherent at 3 months
|
1 Participants
|
—
|
|
Treatment Adherence
Number adherent at 6 months
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Measures at discharge, 1 month, 3 months, and 6 monthsPopulation: Missing data on one AGT subjects
To determine the impact of AGT versus TAU on total number of side effects determined by using the Udvalg for Kliniske Undersogelser (UKU). 1. TAU group reported a total of 8 different side effects, but 11 total events with two subjects over the time frame listed below; the events were expected. (see itemized adverse events) 2. AGT group reported a total of four different side effects and 4 events with one subject over the time frame listed; the events were expected.(see itemized adverse events)
Outcome measures
| Measure |
Treatment as Usual
n=2 Participants
Subjects will be asked to provide blood samples for CYP 450 genotyping; however, the genotyping analysis will occur at a later date.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: genotyping analysis and GWAS analysis was not performed due to early termination of the study)
|
Assay Guided Treatment
n=1 Participants
This test is used to guide clinicians in their recommendations for antidepressant drugs based on CYP 450 gene activity for 1A2, 2C9, 2C19, 2D6, and 3A/4.
Subjects will be asked to provide a blood samples for CYP 450 genotyping. Subjects in the Assay-Guided Treatment group, will have their blood samples genotyped immediately. Their psychiatrists will be given the results of the tests within 3 to 5 days and then they will decide which antidepressants to use.
Subjects will receive questionnaires to measure their mood, side effects, and symptoms.
Subjects will be asked to provide a saliva sample for GWAS analysis at a later date. (note: GWAS analysis was not performed due to early termination of the study)
|
|---|---|---|
|
Adverse Events (Side Effects)
Number of side effects at discharge
|
7 Number of side effects
|
4 Number of side effects
|
|
Adverse Events (Side Effects)
Number of side effects at 1 month
|
1 Number of side effects
|
—
|
|
Adverse Events (Side Effects)
Number of side effects at 3 months
|
1 Number of side effects
|
—
|
|
Adverse Events (Side Effects)
Number of side effects at 6 months
|
2 Number of side effects
|
—
|
Adverse Events
Treatment as Usual (TAU)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Assay Guided Treatment (AGT)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment as Usual (TAU)
n=2 participants at risk
Patients in the TAU group provided blood samples to obtain genotyping to determine the specific activity of genes important in metabolizing antidepressants and to be processed at a later date; however, these blood samples were not analyzed due to the early termination of the study.
Patients received questionnaires to measure their mood, side effects, and symptoms.
Patients provided a saliva sample for GWAS analysis at a later date; however, GWAS analysis was not done due to the early termination of the study.
|
Assay Guided Treatment (AGT)
n=2 participants at risk
Patients in the AGT provided blood samples to obtain genotyping to determine the specific activities of genes important in metabolizing antidepressants. This test was used, at the beginning of treatment to guide clinicians in making recommendations as to which antidepressants and at what doses to prescribe.
Patients received questionnaires to measure their mood, side effects, and symptoms.
Patients in the AGT group provided saliva samples for GWAS analysis; however, GWAS analysis was not done due to the early termination of the study.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Nervous system disorders
Sedation
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
General disorders
Reduced sexual desire
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Psychiatric disorders
Increased dreaming
|
50.0%
1/2 • Number of events 3 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
0.00%
0/2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Gastrointestinal disorders
Dry mouth
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
0.00%
0/2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Gastrointestinal disorders
weight gain
|
50.0%
1/2 • Number of events 2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
0.00%
0/2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Gastrointestinal disorders
Increased appetite
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
0.00%
0/2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Psychiatric disorders
Increased sleep
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
|
Nervous system disorders
Dystonia
|
50.0%
1/2 • Number of events 1 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
0.00%
0/2 • Six months for one subject in the TAU group. Up to 2 weeks for two AGT subjects and one TAU subject. These subjects did not complete 1 month, 3 month, or 6 month follow up visits due to lost to follow up and early termination of the study.
There were no all cause mortality or serious adverse events. All adverse events were expected and measured using the Udvalg for Kliniske Undersogelser (UKU).
|
Additional Information
John D. Matthews, M.D., M.Sc.
Massachusetts General Hospital, Boston, MA
Phone: 617-643-9095
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place