Clinical trial NCT02109939: Genomics Used to Improve DEpression Decisions
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder (MDD)
Keywords: MDD
Pharmacogenomic
Pharmacogenomic Testing
Pharmacogenomics
Genetic Testing
Genetics
Major Depressive Disorder
GeneSight
Assurex
AssureRx
Psychotropic
Randomized
Double Blind
Placebo Controlled
Lead sponsor: Assurex Health Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Michigan
First posted: 2014-04-10
Enrollment: 1398
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks
timeFrame: from baseline to end of Week 8
Secondary outcomes:
measure: Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks
timeFrame: from baseline to end of Week 8
measure: Percentage of Responders at Week 8 for HAM-D17
timeFrame: Week 8 visit info
measure: Percentage of Responders at Week 12 for HAM-D17
timeFrame: Week 12 visit info
measure: Percentage of Remitters at Week 12 Defined as HAM-D17 ≤7
timeFrame: week 12 visit info
measure: Percentage of Remitters at Week 8 Defined as HAM-D17 ≤7 Each Treatment Group;
timeFrame: week 8 visit info
measure: Time to Response/Remission of Depressive Symptoms Over 8 Weeks;
timeFrame: week 4 and 8 visit info
measure: Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 24 Weeks
timeFrame: Baseline to week 24 visits
measure: Percentage of Responders at Week 8 for QIDS-C16
timeFrame: Week 8 visit info
measure: Percentage of Responders at Week 8 for PHQ-9
timeFrame: Week 8 visit info
measure: Percentage of Remitters at Week 12 Defined as QIDS-C16 ≤5
timeFrame: week 12 visit info
measure: Percentage of Remitters at Week 12 Defined as PHQ-9 <5
timeFrame: week 12 visit info
measure: Percentage of Remitters at Week 12 Defined as CGI-S ≤1
timeFrame: week 12 visit info
measure: Percentage of Responders at Week 12 for QIDS-C16
timeFrame: Week 12 visit info
measure: Percentage of Responders at Week 12 for PHQ-9
timeFrame: Week 12 visit info
measure: Percentage of Responders at Week 12 for CGI-S
timeFrame: Week 12 visit info
measure: Percentage of Responders at Week 12 for CGI-I
timeFrame: Week 12 visit info
measure: Percentage of Responders at Week 12 for CGI-EI
timeFrame: Week 12 visit info
measure: Percentage of Remitters at Week 8 Defined as QIDS-C16 ≤ 5 in Each Treatment Group
timeFrame: week 8 visit info
measure: Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group
timeFrame: week 8 visit info
measure: Time to Response/Remission of Depressive Symptoms Over 12 Weeks;
timeFrame: week 4, 8, and 12 visit info
measure: Percentage of Responders at Week 24 for HAM-D17 in the GeneSight Psychotropic Tested Treatment Group
timeFrame: Baseline to week 24 visit info
measure: Percentage of Remitters at Week 24 Defined as HAM-D17 ≤7 in the GeneSight Psychotropic Tested Treatment Group
timeFrame: Baseline to week 24 visit info
Other outcomes:
measure: Generalized Anxiety Disorder 7-item (GAD-7) Scale
timeFrame: week 12 to week 24
measure: Generalized Anxiety Disorder 7-item (GAD-7) Scale
timeFrame: baseline to week 8
measure: Generalized Anxiety Disorder 7-item (GAD-7) Scale
timeFrame: baseline to week 12
Locations:
city: Birmingham
country: United States
facility: Birmingham Psychiatry Pharmaceutical Studies
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Bellflower
country: United States
facility: CiTrials
state: California
city: Chino
country: United States
facility: Catalina Research Institute
state: California
city: Costa Mesa
country: United States
facility: CiTrials
state: California
city: Escondido
country: United States
facility: Synergy Research Center
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Oceanside
country: United States
facility: North County Research
state: California
city: Riverside
country: United States
facility: CiTrials
state: California
city: Stanford
country: United States
facility: Stanford School of Medicine
state: California
city: Temecula
country: United States
facility: Viking Clinical Research
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials, Inc
state: California
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers, LLC
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital Mental Health Clinic
state: District of Columbia
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions Healthcare
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida, Inc
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: West Palm Beach
country: United States
facility: Janus Center For Psychiatric Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Institute of Medicine and Research
state: Georgia
city: Atlanta
country: United States
facility: Mood and Anxiety Program at Emory University
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Schaumburg
country: United States
facility: Behavioral Healthcare Associates
state: Illinois
city: Indianapolis
country: United States
facility: The Institute of Psychiatric Research
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Wichita
country: United States
facility: Kansas University Medical Center- Clinical Trials Unit
state: Kansas
city: Baltimore
country: United States
facility: Pharmasite Research
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Belmont
country: United States
facility: Geriatric Outpatient Unit- McLean Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Center for Psychopharmacologic Research and Treatment
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Bellevue
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute, LLC
state: Nebraska
city: Binghamton
country: United States
facility: United Medical Research Associates
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials, LLC
state: New York
city: Brooklyn
country: United States
facility: SPRI Clinical Trials
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Center, LLC
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Health
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Department of Psychiatry
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mood and Anxiety Disorders Treatment and Research
state: Pennsylvania
city: Lincoln
country: United States
facility: Lincoln Research
state: Rhode Island
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Richmond
country: United States
facility: Alliance Research Group
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Summit Research Network
state: Washington
city: Spokane
country: United States
facility: Frontier Institute
state: Washington
Study officials:
affiliation: University of Michigan
name: John Greden, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dunlop BW, Parikh SV, Rothschild AJ, Thase ME, DeBattista C, Conway CR, Forester BP, Mondimore FM, Shelton RC, Macaluso M, Logan J, Traxler P, Li J, Johnson H, Greden JF. Comparing sensitivity to change using the 6-item versus the 17-item Hamilton depression rating scale in the GUIDED randomized controlled trial. BMC Psychiatry. 2019 Dec 27;19(1):420. doi: 10.1186/s12888-019-2410-2.
citation: Thase ME, Parikh SV, Rothschild AJ, Dunlop BW, DeBattista C, Conway CR, Forester BP, Mondimore FM, Shelton RC, Macaluso M, Li J, Brown K, Jablonski MR, Greden JF. Impact of Pharmacogenomics on Clinical Outcomes for Patients Taking Medications With Gene-Drug Interactions in a Randomized Controlled Trial. J Clin Psychiatry. 2019 Oct 31;80(6):19m12910. doi: 10.4088/JCP.19m12910.
citation: Greden JF, Parikh SV, Rothschild AJ, Thase ME, Dunlop BW, DeBattista C, Conway CR, Forester BP, Mondimore FM, Shelton RC, Macaluso M, Li J, Brown K, Gilbert A, Burns L, Jablonski MR, Dechairo B. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res. 2019 Apr;111:59-67. doi: 10.1016/j.jpsychires.2019.01.003. Epub 2019 Jan 4.