Pharmacogenetic Implementation Trial in Veterans With Treatment Refractory Depression
Primary Purpose
Depression, Depressive Disorder, Depressive Disorder, Major
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Mental Health DNA Insight Test (Pathway Genomics)
Sham Test
Sponsored by
About this trial
This is an interventional treatment trial for Depression focused on measuring pharmacogenetic, pharmacogenomic, genetics
Eligibility Criteria
Inclusion Criteria:
- Age >18
- Veteran
- Psychiatric diagnosis
- Clinically significant depressive symptoms
- Failed 1 or more adequate treatment trials
Exclusion Criteria:
- No clinically significant symptoms of depression
- No previous medication trials
- Pregnancy
- Inpatient medical or psychiatric hospitalization
Sites / Locations
- VA San Diego Healthcare System
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Pharmacogenetic Test Guided
Treatment As Usual
Arm Description
Treating physician for this group receives a detailed pharmacogenetic report for the patient, prioritizing 53 psychoactive medications into 4 use categories: preferential use, use as directed, may have significant limitations, and may have severe adverse reactions.
Treating physician receives a sham report listing the names of all drugs and treats patients according to standard of care.
Outcomes
Primary Outcome Measures
Clinical Global Impression (CGI)
Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
Secondary Outcome Measures
Clinical Global Impression (CGI)
Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
Clinical Global Impression (CGI)
Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
Side Effects Burden
Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
Side Effects Burden
Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
Side Effects Burden
Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
Self Reported Depression Symptoms (scored 1 mild - 27 severe)
Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
Self Reported Depression Symptoms (scored 1 mild - 27 severe)
Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
Self Reported Depression Symptoms (scored 1 mild - 27 severe)
Full Information
NCT ID
NCT04469322
First Posted
July 3, 2020
Last Updated
July 8, 2020
Sponsor
San Diego Veterans Healthcare System
Collaborators
VA Palo Alto Health Care System
1. Study Identification
Unique Protocol Identification Number
NCT04469322
Brief Title
Pharmacogenetic Implementation Trial in Veterans With Treatment Refractory Depression
Official Title
Pharmacogenetic Implementation Trial in Veterans With Treatment Refractory Depression
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
September 30, 2014 (Actual)
Primary Completion Date
June 26, 2018 (Actual)
Study Completion Date
June 26, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
San Diego Veterans Healthcare System
Collaborators
VA Palo Alto Health Care System
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Many patients with depression do not respond well to medication and are diagnosed with treatment refractory depression (TRD). Sometimes medications don't work because an individual metabolizes the drugs in an atypical manner (too fast/slow). Alternatively, drugs may fail to work because the underlying sub-type of depression is not effectively targeted by a medication. This study will use genetic testing of subjects with TRD to personalize the drug treatment of depression and guide the patient to a better clinical outcome. In the guided group, the clinician will receive a pharmacogenetic report to help individually tailor medication selection for TRD patients, potentially allowing the clinician to pick more effective medications right away, and when necessary, use drug combinations that are well-tolerated and less likely to cause unwanted side effects. The control group will receive a sham genetic report and be treated according to typical standards of care. The investigators will conduct our study in a "real world" setting, with few restrictions on which TRD patients can participate. In this way, the findings may be more likely to reveal how useful genetic testing will be when applied more broadly in psychiatry.
Detailed Description
Study Design and Methods. The investigators will use prospective methods to assess the utility of pharmacogenetic guided treatment (PGT) of TRD. The use of genetic testing for PGT subjects, and clinical care guided by the individual's genetic results are the only subject activities in this study that represent a departure from standard clinical care. Other activities carried out within the context of this study are conducted in accordance with accepted clinical practice by a trained and licensed psychiatrist. These include (but are not limited to) the use of prescription medications, laboratory testing, vital sign measurements, mood scales and diagnostic interviews, electrocardiograms, and imaging studies. Standard clinical activities will be conducted at the discretion of the attending psychiatrist, determined by the clinical needs of the individual patient. All laboratory testing conducted for the purposes of clinical treatment (diagnosis, treatment, and prevention of illness) will be conducted at the VA San Diego or VA Palo Alto accredited clinical laboratories. No investigational medications or devices will be used in this study.
Setting: Clinical care will be conducted at the Veterans Affairs San Diego Healthcare System and Veterans Affairs Palo Alto Healthcare . Patients with TRD will be recruited from multiple sites in the local VA Systems. Clinical care will be provided by a VA psychiatrist.
Genotyping: After obtaining written consent, patients will give a saliva sample from which genomic DNA is prepared using established protocols. DNA samples will be assigned a coded subject identification number that will not contain any sensitive personal information. The code key will remain at the VASDHS at all times. Samples will be sent to a CLIA certified laboratory (Pathway Genomics) for genotyping and analyzed using the commercially available Mental Health DNA Insight Test. Unused DNA sent for genotyping will be destroyed. No DNA storage outside the VASDHS will be permitted. No other clinically relevant information will be uncovered by the genetic testing.
Randomization & Study Design: Patients will be randomly assigned to one of two groups: Pharmacogenetic guided treatment (PGT) and treatment as usual (TAU). All patients will provide a saliva sample at the start of their participation 5-7 days before their initial clinic appointment: All subjects will be genotyped and analyzed using the Mental Health DNA Insight Test. The treating physician for the PGT group will receive the report before the first clinic visit. The treating physician for the TAU group will receive a sham report.
Patients will remain blind into which treatment group they are assigned until completion of the study. The study physicians will not be blinded due to the need to review the PGT report. However, bias will be reduced by using patient self-reports of their mood using the 16-item quick inventory of depressive symptoms self report (QIDS-SR16) scale. All patients will then be seen by a study psychiatrist at 4 weeks and 8 weeks follow-up. All patients will complete self assessment inventories at each visit. In addition they will assess tolerability using a standardized side effect checklist. Overall functional impairment and symptom severity will be assessed using the Clinical Global Impressions Scale (CGI). Primary study outcome will be the CGI score at the end of the study (8 weeks). A Comprehensive Suicide Risk Assessment will be done at study initiation and a clinical suicidality assessment will be conducted at every visit according to usual clinical practice.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Depressive Disorder, Depressive Disorder, Major, Depression, Bipolar, Depressive Episode
Keywords
pharmacogenetic, pharmacogenomic, genetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
randomized, single blind, multi-center, prospective
Masking
Participant
Masking Description
patient blinded to condition
Allocation
Randomized
Enrollment
182 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pharmacogenetic Test Guided
Arm Type
Experimental
Arm Description
Treating physician for this group receives a detailed pharmacogenetic report for the patient, prioritizing 53 psychoactive medications into 4 use categories: preferential use, use as directed, may have significant limitations, and may have severe adverse reactions.
Arm Title
Treatment As Usual
Arm Type
Sham Comparator
Arm Description
Treating physician receives a sham report listing the names of all drugs and treats patients according to standard of care.
Intervention Type
Diagnostic Test
Intervention Name(s)
Mental Health DNA Insight Test (Pathway Genomics)
Intervention Description
Pharmacogenetic report based on the patients DNA profile at ~45 SNP markers covering 16 genes
Intervention Type
Diagnostic Test
Intervention Name(s)
Sham Test
Intervention Description
Names of 53 medications listed with "use as directed"
Primary Outcome Measure Information:
Title
Clinical Global Impression (CGI)
Description
Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Clinical Global Impression (CGI)
Description
Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
Time Frame
0 weeks
Title
Clinical Global Impression (CGI)
Description
Observer rated 7 item scale indicating overall clinical severity of depression (1 asymptomatic - 7 severe)
Time Frame
4 weeks
Title
Side Effects Burden
Description
Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
Time Frame
0 weeks
Title
Side Effects Burden
Description
Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
Time Frame
4 weeks
Title
Side Effects Burden
Description
Total of Side Effects Using Standardized Scale (scored 0 asymptomatic - 37 severe)
Time Frame
8 weeks
Title
Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
Description
Self Reported Depression Symptoms (scored 1 mild - 27 severe)
Time Frame
0 weeks
Title
Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
Description
Self Reported Depression Symptoms (scored 1 mild - 27 severe)
Time Frame
4 weeks
Title
Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR16)
Description
Self Reported Depression Symptoms (scored 1 mild - 27 severe)
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >18
Veteran
Psychiatric diagnosis
Clinically significant depressive symptoms
Failed 1 or more adequate treatment trials
Exclusion Criteria:
No clinically significant symptoms of depression
No previous medication trials
Pregnancy
Inpatient medical or psychiatric hospitalization
Facility Information:
Facility Name
VA San Diego Healthcare System
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33938307
Citation
McCarthy MJ, Chen Y, Demodena A, Leckband SG, Fischer E, Golshan S, Suppes T, Kelsoe JR. A prospective study to determine the clinical utility of pharmacogenetic testing of veterans with treatment-resistant depression. J Psychopharmacol. 2021 Aug;35(8):992-1002. doi: 10.1177/02698811211015224. Epub 2021 May 3.
Results Reference
derived
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Pharmacogenetic Implementation Trial in Veterans With Treatment Refractory Depression
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