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Clinical Utility of Pharmacogenomics of Psychotropic Medications

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03907124
Recruitment Status : Recruiting
First Posted : April 8, 2019
Last Update Posted : July 23, 2019
Information provided by (Responsible Party):
Mujeeb U Shad, MD, MSCS, Oregon Health and Science University

Brief Summary:

While the scientific understanding of pharmacogenomics is quickly accelerating, its translation to clinical decision-making (especially in psychiatric practice) has progressed more slowly. In an effort to begin to bridge this translational gap, genetic testing has been developed for various and commonly existing psychiatric disorders, such as major depression, schizophrenia, bipolar disorder, and pain syndromes to improve the safety of prescribing psychotropic medications for these disorders. This genetic testing incudes several pharmacodynamics and pharmacokinetic genetic factors, such as the cytochrome P450 1A2 gene (CYP1A2); the cytochrome P450 2B6 (CYP2B6) gene; P450 2D6 gene (CYP2D6); the cytochrome P450 2C9 gene (CYP2C9); the cytochrome P450 2C19 gene (CYP2C19); uridine-glucoronyl-transferase 2B15 (UGT2B15) gene; the serotonin transporter gene (Solute Carrier Family 6 Member; SLC6A4); p-glycoprotein ( ATP-binding cassette sub-family B member 1; ABCB1) transporter gene; the serotonin 2A receptor gene (HTR2A); the serotonin 2C receptor (HTR2C) gene; serotonin 1a receptor (5HT1a) gene; dopamine 1 receptor (DRD1) gene; dopamine 2 receptor (DRD2) gene; adrenergic alpha-2A receptor (alpha-2A) gene; opioid mu (opioid receptor mu 1; OPRM1) receptor gene; dopamine synthesis gene (ankyrin repeat and kinase domain containing 1; ANKK1); dopamine metabolizing enzyme [Catechol-o-methyltransferase (COMT]) gene; kainite receptor gene (glutamate ionotropic receptor kainate type subunit 4; GRIK4); folate (methylenetetrahydrofolate reductase; MTHFR) gene; sodium channels (sodium voltage-gated channel alpha subunit 2; SCN2A) gene.

The interpretive report is based on copies of these multiple informative genes. The investigators are proposing to utilize comprehensive genetic testing to select more genetically-informed psychotropic medications to enhance their effectiveness in real-world patients with psychiatric illnesses such as schizophrenia, major depression, bipolar affective disorder as well as pain in a state hospital setting. The investigators plan to use genetic testing offered by Admera® for major classes of psychotropic medications. The investigators hypothesize that genetic testing will demonstrate clinical benefits by improving state hospital patients' response and decreasing their adverse effects. The proposed study will be conducted in a total sample of 60 subjects diagnosed with schizophrenia, major depression, bipolar affective disorder as well as pain at the Oregon State Hospital, Salem Oregon over a total period of 24 months

Condition or disease Intervention/treatment Phase
Psychiatric Disorders Pain Drug: Genetically-guided treatment with FDA-approved psychotropic drugs Drug: Treatment as usual (TAU) Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomized prospective cohort study which will compare the utility of an interpretive report based on pharmacogenomic testing between study subjects receiving psychotropic medication with guidance from an interpretive report (i.e., Genetically-Guided Group) and those receiving psychotropic medications without the implementation of the interpretive report (Genetically-Unguided Group).
Masking: Single (Outcomes Assessor)
Masking Description: The study raters will be kept blinded to the two arms of the study to avoid assessment bias.
Primary Purpose: Treatment
Official Title: Clinical Utility of Pharmacogenomics of Psychotropic Medications
Actual Study Start Date : June 3, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : February 2021

Arm Intervention/treatment
Experimental: Genetically-guided treatment arm
The active arm - where patients will receive genetically-guided treatment
Drug: Genetically-guided treatment with FDA-approved psychotropic drugs
Psychiatric patients in this experimental arm will receive genetically-guided treatment with psychotropic medications

Drug: Treatment as usual (TAU)
All subjects assigned to TAU group, which is the control arm, will continue to receive FDA-approved psychotropic medications for psychiatric indications investigated in this study
Other Name: standard of care treatment with FDA-approved psychotropic drugs

No Intervention: Treatment as usual (TAU) control arm
TAU is the control arm - where patients will continue to receive their usual treatment as before.

Primary Outcome Measures :
  1. Positive Subscale of Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 15 minutes ]
    PANSS is one of the most widely clinical scales to monitor positive and negative symptoms of schizophrenia. The scores range from 30 to 210. A score of 58 is considered mildly ill; 75 is moderately ill and 95 is markedly ill; and 116 is severely ill. This study will only use the scores from positive subscale (range 7 to 49) and the eligibility criteria will require a moderate score on 4 positive sub-scale items, including hallucinations, delusions, suspiciousness and conceptual disorganization to qualify for the study.

  2. Behavioral Assessment of Pain Screening Instrument (BAPSI) [ Time Frame: 10 minutes ]
    This scale assesses level of pain-related disability, psychological distress, and pain intensity. 0 - 3 = minimal levels of average pain intensity; 4 - 6 = moderate levels of average pain intensity; 7 - 10 = severe levels of average pain intensity.

  3. Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: 10 minutes ]

    This is a scale to assess severity of anxiety symptoms. Total score=21; 5-9 = Mild; 10-14 = Moderate; >15 = Severe

    *For Panic Disorder, Social Phobia, & PTSD, cutoff score of 8 may be used for optimal sensitivity/specificity (see Evidence section).

    Critical Actions

    This tool should be used for screening and monitoring symptom severity and cannot replace a clinical assessment and diagnosis.

    Do not forget to rule out medical causes of anxiety before diagnosing an anxiety disorder (for example, EKG for arrhythmias, TSH for thyroid disease).

  4. Public Health Questionnaire-9 (PHQ-9) [ Time Frame: 10 minutes ]
    This is a commonly used scale in clinical practice to assess depressive symptoms. The total score is 36. Score of 0-4 = Minimal or no depressive symptoms; 5-9 = Mild symptoms; 10-14 = moderate symptoms; 15-19 = Moderately severe symptoms; 20-27 = severe symptoms.

Secondary Outcome Measures :
  1. Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) [ Time Frame: 5 minutes ]
    CGI-S will be used to assess severity o illness at baseline. The total score ranges from 0 to 7, where 0 is not assessed; 3 is mildly ill; 5 is markedly ill; and 7 is most extensively ill. While CGI-I is is scored from 0 to 7, where 0 is not assessed; 1 is very much improved; 3 is minimally improved; 5 is minimally worse and 7 is very much worse.

  2. Self-Report Quality of Life Scale (SQLS) [ Time Frame: 5 minutes ]
    This is a 30-item questionnaire, comprising three scales ('psychosocial', 'motivation and energy', and 'symptoms and side-effects') addressing different SQLS dimensions. Each quality of life item is scored from 0 to 4, where 0 is not assessed, 1 is rare; 2 is sometimes, 3 is often and 4 is frequently. The score can range from 0 to 120, where higher scores reflect lower quality of life.

  3. Social & Occupational Functional Assessment Scale (SOFAS) [ Time Frame: 7 minutes ]
    SOFAS focuses exclusively on the individual's level of social and occupational functioning and is not directly influenced by the overall severity of the individual's psychological symptoms. It is scored from 0 to 100, where 100 = Superior functioning in a wide range of activities; 80 = No more than a slight impairment in social, occupational, or school functioning (e.g., infrequent interpersonal conflict, temporarily falling behind in schoolwork); 60 is Moderate difficulty in social, occupational, or school functioning (e.g., few friends, conflicts with peers or co-workers); 40 = Major impairment in several areas, such as work or school, family relations; and 20 = Occasionally fails to maintain minimal personal hygiene; unable to function independently.

  4. Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: 7 minutes ]
    The AIMS is a 12-item clinician-rated scale to assess severity of EPS, especially dyskinesias in patients taking neuroleptic medications. It also assesses overall severity, incapacitation, and the patient's level of awareness of the movements, and distress associated with them. Items are scored on a 0 (none) to 4 (severe) basis; the scale provides a total score (items 1 through 7) or item 8 can be used in isolation as an indication of overall severity of symptoms.

  5. UKU Side Effect Rating Scale (USERS) [ Time Frame: 10 minutes ]
    USERS is a comprehensive scale to assess side effects from medications. It is composed of several sub-scales but in this study we will only use the sub-scales that are frequently associated with neuroleptic medications i.e., psychic (10 items), neurologic (8 items) and autonomic (11 items). Each item is scores as 9, 0, 1, 2 and 3, the higher number represents a subjectively reported increase in frequency of respective side effect.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient is between the ages of 18 and 80
  • Schizophrenia or schizoaffective disorder, major depressive disorder, bipolar affective disorder as ascertained by a qualified physician or mental health professional licensed to diagnose based on DSM-V criteria.
  • Patients using antidepressants, anxiolytics, mood stabilizers, and sedative/hypnotics will be allowed
  • Patients on clozapine treatment will be allowed.
  • Study subjects with a score of at least 12 on the scale to assess capacity to consent i.e., UBACC.

Exclusion Criteria:

  • Patients who are court-committed for involuntary medications
  • Uncontrolled and/or serious medical illness (as ascertained at admission screening process)
  • Pregnant patients
  • Patients who cannot communicate in English.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03907124

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Contact: Mujeeb U Shad, MD, MSCS 5039472998
Contact: Roy Kamalika, MD 503-947-2998

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United States, Oregon
Mujeeb Uddin Shad Recruiting
Salem, Oregon, United States, 97301
Contact: Mujeeb U Shad, MD, MSCS    503-947-2998   
Sponsors and Collaborators
Oregon Health and Science University
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Principal Investigator: Mujeeb U Shad, MD, MSCS Psychiatry

Mrazek DA. Psychiatric Pharmacogenomics. New York, NY: Oxford University Press; 2010.
Rundell JR, Shinozaki G. Pharmacogenomic considerations in patients with both comorbid medical and psychiatric illness. Prim Psychiatry 2010; 17:33-38

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Responsible Party: Mujeeb U Shad, MD, MSCS, Associate Professor of Psychiatry, Oregon Health and Science University Identifier: NCT03907124     History of Changes
Other Study ID Numbers: STUDY00018828
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mujeeb U Shad, MD, MSCS, Oregon Health and Science University:
Additional relevant MeSH terms:
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Mental Disorders
Problem Behavior
Behavioral Symptoms
Psychotropic Drugs