Genomics Used to Improve DEpression Decisions

Major Depressive Disorder (MDD) Clinical Trial

— GUIDED  

Official title:

12 Week, Randomized, Double-Blind, Controlled Evaluation Followed by an Open Label 12-Week Follow-up Period of the Impact of GeneSight Psychotropic on Response to Psychotropic Treatment in Outpatients Suffering From A Major Depressive Disorder (MDD) Having Had- Within the Current Episode- An Inadequate Response to at Least One Medication Included in GeneSight Psychotropic

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02109939
• Other study ID #: ARX1006
• Status: Completed
• Phase: N/A
• Start date: April 2014
• Est. completion date: July 31, 2017

Study information

• Verified date: January 2020
• Source: Assurex Health Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 8 of the study.

Description:

Major depressive disorder (MDD) is a highly prevalent (Hasin et al., 2005) mental disorder and a leading source of disease burden worldwide (Lopez et al., 2006). Epidemiological studies estimate 12-month and lifetime prevalence for MDD in the United States to be 5.3% and 13.2%, respectively (reviewed in Blanco et al., 2010). MDD is expected to be the second greatest cause of disability by 2020 and has been shown to cause significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, MDD increases the risk of suicidal ideation, attempted suicide, and death by completed suicide.

Prospective longitudinal studies of patient samples show that MDD is a chronic illness, characterized by remitting and recurrent depressive episodes (Solomon et al., 1997; Mueller et al., 1999). A major depressive episode is characterized by a low mood or an inability to experience pleasure (anhedonia), or both, for more than 2 weeks, combined with several cognitive and vegetative symptoms and the occurrence of distress or impairment (reviewed in Rot et al., 2009). In the US, nearly 1 in 5 people will experience a major depressive episode at some point in their lives (reviewed in Rot et al., 2009). Drugs currently available to treat depression fall into the categories of those that have their main effect by increasing norepinephrine (NE) (the tricyclic or tetracyclic antidepressants [TCAs]), those that increase serotonin (5-HT) (the selective serotonin reuptake inhibitors [SSRIs]), and those that increase both NE and 5-HT (the monoamine oxidase inhibitors [MAOIs] and the serotonin and norepinephrine reuptake inhibitors [SNRIs]). While all antidepressants achieve similar levels of efficacy, treatment failures are relatively high ranging from 30 to 60% (Simpson and DePaulo). Additionally, many of these compounds are associated with significant adverse events (AEs).

The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications.

The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes.

Tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

The clinical utility of GeneSight Psychotropic has been evaluated in three previous prospective trials. Hall-Flavin et al reported the results of an open-label pilot study (n = 44) comparing GeneSight guided treatment to treatment as usual (TAU) without the benefit of pharmacogenomic testing (2012). The GeneSight guided arm demonstrated a 30.8% improvement in HAM-D17 score by the end of the 8 week treatment period, compared to an 18.2% improvement in the TAU arm (p = 0.04). Results of the larger (n = 165) open-label trial (Hall-Flavin, et al 2013) mirrored these findings, demonstrating a 46.9% improvement in HAMD17 score in the GeneSight arm, compared to a 29.9% improvement in the TAU arm (p < 0.0001). The third trial used a randomized, double-blind trial design (n = 51). Due to the small sample size, the trial was underpowered to detect a significant difference in improvement between the two arms (TAU and GeneSight). However, effect sizes of improvement reflected those seen in previous trials. The GeneSight group experienced a 30.8% improvement in HAMD17, compared to 20.7% in TAU. Odds ratios for response were calculated, showing that GeneSight-guided subjects had a 2.14 times greater likelihood of response compared to TAU subjects, which was similar to the 4.67 (smaller trial) and 2.06 (larger trial) odds ratios calculated for the other two studies.

Previous studies utilizing an open-label design have shown significant improvement in patient outcomes following use of the GeneSight test. However, although effect sizes were similar to those seen in the open-label studies, a small (n = 51) blinded, randomized controlled trial did not detect a statistically significant outcome. Therefore, the primary rationale for this trial is to replicate previous findings of improvement in clinical outcomes in subjects treated with the benefit of GeneSight testing utilizing a double-blind, randomized control trial (RCT) design.

It is expected that results from this trial will be used to inform guidelines for the use of pharmacogenomic testing for the treatment of major depressive disorder. Results may also be shared with regulatory bodies in the United States and abroad.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1398
• Est. completion date: July 31, 2017
• Est. primary completion date: April 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Be able to understand the requirements of the study and provide written informed consent to participate in this study; a signed and dated ICF will be obtained from each patient before participation in the study;

• Have provided written authorization for the use and disclosure of their protected health information;

• Be =18 years of age;

• Suffer from a Major Depressive Episode meeting DSM-IV-TR criteria;

• Have had an inadequate response within the current episode to at least 1 psychotropic treatment. Inadequate response is defined as inadequate efficacy after 6 weeks of a psychotropic treatment or discontinuation of a psychotropic treatment due to AEs or intolerability;

• Have a total baseline score on the QIDS-C16 and QIDS-SR16 rating scale =11;

• Agree to abide by the study protocol and its restrictions and be able to complete all aspects of the study, including all visits and tests.

Exclusion Criteria:

• Patients posing a serious suicidal risk and/or in need of immediate hospitalization as judged by the investigator;

• Patients with a diagnosis of Bipolar I or II disorder;

• Patients with a current Axis I diagnosis of:

1. Delirium

2. Dementia

3. Amnestic and other cognitive disorder

4. Schizophrenia or other psychotic disorder;

• Patients having experienced hallucinations, delusions, or any psychotic symptomatology within the current depressive episode or during prior depressive episodes;

• Patient is currently in an inpatient facility;

• Patients with a history of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic or euthyroid for 6 months;

• Patients who meet DSM-IV-TR criteria for any significant current substance use disorder;

• Patients with significant unstable medical condition; life threatening disease; hepatic insufficiency (3X ULN for AST and/or ALT); liver transplant recipient; cirrhosis of the liver; need for therapies that may obscure the results of treatment and/or of the study; malignancy (except basal cell carcinoma) and/or chemotherapy within 1 year prior to screening; malignancy more than 1 year prior to screening must have been local and without metastasis and/or recurrence, and if treated with chemotherapy, without nervous system complications;

• Participation in another clinical trial within 30 days of the screening visit;

• Anticipated inability to attend scheduled study visits;

• Patients who in the judgment of the Investigator may be unreliable or uncooperative with the evaluation procedure outlined in this protocol;

• Patients with a history of prior pharmacogenomic testing;

• Any change in psychotropic medication (including change in dosage) between screening and randomization;

• Patients receiving ECT, DBS or TMS treatment (should a Subject receive any of these treatments they must be discontinued from the study);

• Patients who are known to be pregnant or lactating;

• Patients with a history of gastric bypass surgery.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder (MDD)

Intervention

Genetic:
• GeneSight Psychotropic
The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Atlanta Institute of Medicine and Research	Atlanta	Georgia
United States	Mood and Anxiety Program at Emory University	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Pharmasite Research	Baltimore	Maryland
United States	Meridian Clinical Research	Bellevue	Nebraska
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	CiTrials	Bellflower	California
United States	Geriatric Outpatient Unit- McLean Hospital	Belmont	Massachusetts
United States	United Medical Research Associates	Binghamton	New York
United States	Birmingham Psychiatry Pharmaceutical Studies	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Integrative Clinical Trials, LLC	Brooklyn	New York
United States	SPRI Clinical Trials	Brooklyn	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	Catalina Research Institute	Chino	California
United States	University of Cincinnati Health	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	MCB Clinical Research Centers, LLC	Colorado Springs	Colorado
United States	Ohio State University Department of Psychiatry	Columbus	Ohio
United States	CiTrials	Costa Mesa	California
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Synergy Research Center	Escondido	California
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	The Institute of Psychiatric Research	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Clinical Neuroscience Solutions Healthcare	Jacksonville	Florida
United States	Lincoln Research	Lincoln	Rhode Island
United States	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska
United States	Pharmacology Research Institute	Los Alamitos	California
United States	Suburban Research Associates	Media	Pennsylvania
United States	Clinical Neuroscience Solutions	Memphis	Tennessee
United States	University of Minnesota	Minneapolis	Minnesota
United States	Eastside Comprehensive Medical Center, LLC	New York	New York
United States	North County Research	Oceanside	California
United States	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions	Orlando	Florida
United States	Mood and Anxiety Disorders Treatment and Research	Philadelphia	Pennsylvania
United States	Summit Research Network	Portland	Oregon
United States	Alliance Research Group	Richmond	Virginia
United States	CiTrials	Riverside	California
United States	Finger Lakes Clinical Research	Rochester	New York
United States	PsychCare Consultants Research	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Meridian Clinical Research	Savannah	Georgia
United States	Behavioral Healthcare Associates	Schaumburg	Illinois
United States	Summit Research Network	Seattle	Washington
United States	Carman Research	Smyrna	Georgia
United States	Frontier Institute	Spokane	Washington
United States	Stanford School of Medicine	Stanford	California
United States	Clinical Research Trials of Florida, Inc	Tampa	Florida
United States	Stedman Clinical Trials	Tampa	Florida
United States	Viking Clinical Research	Temecula	California
United States	Howard University Hospital Mental Health Clinic	Washington	District of Columbia
United States	Janus Center For Psychiatric Research	West Palm Beach	Florida
United States	Kansas University Medical Center- Clinical Trials Unit	Wichita	Kansas
United States	Elite Clinical Trials, Inc	Wildomar	California
United States	UMASS Center for Psychopharmacologic Research and Treatment	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Assurex Health Inc.	University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Generalized Anxiety Disorder 7-item (GAD-7) Scale	The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from week 12 to week 24	week 12 to week 24
Other	Generalized Anxiety Disorder 7-item (GAD-7) Scale	The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from baseline to week 8	baseline to week 8
Other	Generalized Anxiety Disorder 7-item (GAD-7) Scale	The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from baseline to week 12	baseline to week 12
Primary	Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks	Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean percent change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 8 of the study. Scores range from 0 to 50, and lower scores are better outcomes. Percent change is defined as (week 8 score -baseline score) / (baseline score) x 100.	from baseline to end of Week 8
Secondary	Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks	Mean percent change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) score from baseline to end of Week 8 of the study. Scores range from 0 to 27 with lower scores being better outcomes. Percent change is defined as (week 8 score - baseline score) / (baseline score) x 100.	from baseline to end of Week 8
Secondary	Percentage of Responders at Week 8 for HAM-D17	Adjusted percentage of responders at Week 8 in each treatment group on the 17-item Hamilton Depression Rating Scale (HAM-D17). A responder is defined as a participant with at least a 50% decrease from baseline in total scale score. Scores range from 0 to 50, and lower scores are better outcomes.	Week 8 visit info
Secondary	Percentage of Responders at Week 12 for HAM-D17	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	Week 12 visit info
Secondary	Percentage of Remitters at Week 12 Defined as HAM-D17 =7	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	week 12 visit info
Secondary	Percentage of Remitters at Week 8 Defined as HAM-D17 =7 Each Treatment Group;	Adjusted percentage of remitters at Week 8 defined as a score =7 in the 17-item Hamilton Depression Rating Scale (HAM-D17) in each treatment group. Scores range from 0 to 50, and lower scores are better outcomes.	week 8 visit info
Secondary	Time to Response/Remission of Depressive Symptoms Over 8 Weeks;	*Comment*: Time to response/remission is not an outcome measure that can accurately be reported from the way the data was collected. As specified in the updated SAP before the blind was broken, this was not analyzed or reported.	week 4 and 8 visit info
Secondary	Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 24 Weeks	Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean percent change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 24 of the study. Scores range from 0 to 50, and lower scores are better outcomes. Percent change is defined as (week 24 score -baseline score) / (baseline score) x 100.	Baseline to week 24 visits
Secondary	Percentage of Responders at Week 8 for QIDS-C16	Adjusted percentage of responders at Week 8 in each treatment group on the 16-item Quick Inventory of Depression Symptomology (QIDS-C16). A responder is defined as a participant with at least 50% decrease from baseline in total scale score. Scores range from 0 to 27 with lower scores being better outcomes.	Week 8 visit info
Secondary	Percentage of Responders at Week 8 for PHQ-9	Adjusted percentage of responders at Week 8 in each treatment group on the 9-item Patient Health Questionnaire (PHQ-9). A responder is defined as a participant with at least 50% decrease from baseline in total scale score. Scores range from 0 to 27 with lower scores being better outcomes.	Week 8 visit info
Secondary	Percentage of Remitters at Week 12 Defined as QIDS-C16 =5	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	week 12 visit info
Secondary	Percentage of Remitters at Week 12 Defined as PHQ-9 <5	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	week 12 visit info
Secondary	Percentage of Remitters at Week 12 Defined as CGI-S =1	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	week 12 visit info
Secondary	Percentage of Responders at Week 12 for QIDS-C16	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	Week 12 visit info
Secondary	Percentage of Responders at Week 12 for PHQ-9	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	Week 12 visit info
Secondary	Percentage of Responders at Week 12 for CGI-S	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	Week 12 visit info
Secondary	Percentage of Responders at Week 12 for CGI-I	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	Week 12 visit info
Secondary	Percentage of Responders at Week 12 for CGI-EI	*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.	Week 12 visit info
Secondary	Percentage of Remitters at Week 8 Defined as QIDS-C16 = 5 in Each Treatment Group	Adjusted percentage of remitters at Week 8 in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) in each treatment group. A remitter is defined as a subject with a score = 5. Scores range from 0 to 27 with lower scores being better outcomes.	week 8 visit info
Secondary	Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group	Adjusted percentage of remitters at Week 8 in each treatment group on the 9-item Patient Health Questionnaire (PHQ-9). A remitter is defined as a participant with score <5 on the PHQ-9. Scores range from 0 to 27 with lower scores being better outcomes.	week 8 visit info
Secondary	Time to Response/Remission of Depressive Symptoms Over 12 Weeks;	*Comment*: Time to response/remission is not an outcome measure that can accurately be reported from the way the data was collected. As specified in the updated SAP before the blind was broken, this was not analyzed and reported. Additionally, for patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding may have occurred prior to week 12 assessments, data collected at week 12 were considered unblinded and are not reported.	week 4, 8, and 12 visit info
Secondary	Percentage of Responders at Week 24 for HAM-D17 in the GeneSight Psychotropic Tested Treatment Group	Adjusted percentage of responders at Week 24 in the GeneSight Psychotropic Tested treatment group on the 17-item Hamilton Depression Rating Scale (HAM-D17). A responder is defined as a participant with at least a 50% decrease from baseline in total scale score. Scores range from 0 to 50, and lower scores are better outcomes.	Baseline to week 24 visit info
Secondary	Percentage of Remitters at Week 24 Defined as HAM-D17 =7 in the GeneSight Psychotropic Tested Treatment Group	Adjusted percentage of remitters at Week 8 defined as a score =7 in the 17-item Hamilton Depression Rating Scale (HAM-D17) in each treatment group. Scores range from 0 to 50, and lower scores are better outcomes.; *Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding may have occurred prior to week 12 assessments, all data collected at week 12 were considered unblinded and are not reported.	Baseline to week 24 visit info