Pharmacogenomics for Antidepressant Guidance and Education

This study is currently recruiting participants.
Verified November 2013 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
John D. Matthews, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01555021
First received: February 16, 2012
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

More than one out of three individuals treated for major depressive disorder (MDD) do not experience a full reduction of symptoms even when treated with adequate antidepressant medication. These individuals may have treatment-resistant depression. This is a condition that contributes to the tremendous costs of MDD, in terms of health care costs, functional impairment (limitation of an individual's functional ability), and diminished quality of life.

There is a clear need for personalized medicine, for people at high risk for treatment-resistant depression. If these individuals could be identified early in the course of their depression, they could be recommended for more intensive or specialized interventions. Doing so could improve their likelihood of having a full reduction in their symptoms.

Today, there are many treatment options for MDD. Individuals can spend months or years in and out of treatment before receiving one that works for their treatment-resistant depression.

The investigators want to study treatment resistant depression by examining specific genes (genotyping) that might influence how your body responds to certain antidepressant medications. This process of examining specific genes is not experimental. To look at your specific genes, the investigators will collect a saliva sample. Genes contain the material passed from parent to child that determines the make-up of the body and mind. For example, some genes control the color of your hair or eyes. Genes are contained in your DNA (deoxyribonucleic acid). There are many differences in DNA, from one person to another. These differences may affect a person's chances of having a particular disease.


Condition Intervention
Treatment Resistant Depression
Genetic: Genotyping assays

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Pharmacogenomics for Antidepressant Guidance and Education

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Reduction in Quick Inventory of Depressive Symptoms-15 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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)15, adjusted for baseline severity, weekly, upon discharge, and at 1, 3, and 6 months post discharge from inpatient treatment.


Secondary Outcome Measures:
  • Clinician behavior [ Time Frame: Measured: +/- 24 hours of baseline assessments and +/- 24 hours of receiving assay results ] [ Designated as safety issue: No ]
    To estimate the proportion of subjects in whom AGT versus TAU leads to a change in clinician behavior, in terms of initial treatment type or dosage.

  • Treatment Adherence [ Time Frame: Measured: Discharge (7-10 days after admission +/- 24 hours) and 1, 3, 6 months after discharge (+/- 4 weeks) ] [ Designated as safety issue: No ]
    To determine the impact of AGT versus TAU on postdischarge treatment adherence over 6 months.

  • Side Effects [ Time Frame: 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) ] [ Designated as safety issue: No ]
    To determine the impact of AGT versus TAU on side effect measures with the UKU.


Estimated Enrollment: 200
Study Start Date: December 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Treatment as Usual
Experimental: Assay Guided Treatment
This group will receive a genotyping test to determine the specific levels of genes in their systems. This test is used to guide clinicians in the recommendation of psychotropic drugs.
Genetic: Genotyping assays

Patients will be asked for a saliva sample. If the patient is in the Assay-Guided Treatment group (as opposed to the Treatment as Usual group), their saliva will be genotyped. Their psychiatrists will be given the results of the tests and then they will decide which antidepressants to use. The genotyping test is a one-time occurrence that happens at the beginning of the study. Patients who are in the Treatment as Usual group will have their saliva samples stored.

Patients will receive questionnaires to measure their mood, side effects, and symptoms.

Patients will be asked for a blood sample. Those in the AGT group will have the sample processed to see the amount of antidepressant present in their blood. Those in the TAU group will have their blood samples stored for future use.

Patients will be asked to participate in 3 follow-up phone calls to measure their mood.

Other Names:
  • Genecept assay
  • Oragene saliva test kit

Detailed Description:

This will be a 6-month, randomized, controlled study of assay-guided treatment (AGT) versus treatment as usual (TAU) in adult inpatients with major depressive disorder. Two hundred subjects will be randomized to receive AGT or TAU. After subjects are screened, determined to be eligible, and complete baseline assessments, saliva samples for assay will be obtained from all subjects. However, only those subjects that are randomized to the AGT arm will have the saliva samples immediately analyzed. Subjects in the TAU arm will have their saliva samples stored for future GWAS analysis.

Once the saliva samples are obtained, the attending psychiatrists will be asked to indicate their top three choices of antidepressants and at what doses they will initiate treatment. In order to prevent delays in providing treatments, the first choice antidepressants will be started prior to receiving assay results.

Upon receiving the assay reports (AGT arm), the attending psychiatrists will be asked whether the reports influenced their choice of antidepressant treatments and doses of antidepressants, as well as their confidence in their choices. The attending psychiatrists will then document any switches in antidepressant treatments or changes in doses of current antidepressant medications on a structured form. The assay reports will be available between 3 to 5 days after the saliva samples are taken. The attending psychiatrists who are randomized to be provided the results of CYP genotyping will also be provided a phone number for consultation with Genomind Labs regarding the interpretation of the results.

Trough antidepressant blood samples for the AGT arm (10-12 hours after last dose) for therapeutic drug monitoring (TDM) will be obtained within 24 hours of discharge. Blood samples will also be obtained from the TAU arm, but they will be stored for future analysis of CYP genotyping and biomarker analysis of treatment resistant MDD. Clinical follow-up will proceed as felt to be clinically indicated. For subjects who have been discharged before the assay results are received, the attending psychiatrists will complete the from indicating changes in treatments as if patients were still in hospital. Results and recommendations will be forwarded to the identified outpatient psychiatrists.

The AGT arm is not standard care for patients with depression. The addition of assay-results and questionnaires makes the AGT arm different than standard care. Only the questionnaires make the TAU arm different than standard care.

Note:

Within 24 hours after you are admitted to the Inpatient Psychiatric Unit, the "baseline" assessment will occur. If you stay in the Inpatient Psychiatric Unit for more than one week, the "weekly" assessment will occur every 7 days. Typically, patients spend an average of 8-10 days in the Inpatient Psychiatric Unit. The day before or the day of your discharge from the Inpatient Psychiatric Unit, your "discharge" assessment will occur. One, 3, and 6 months after you are discharged, you will be asked to complete follow-up assessments.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-70
  • Written informed consent
  • Meets DSM-IV criteria in the Structured Clinical Interview for DSM-IV-TR (SCID-I/P)17 and the MINI for current major depressive disorder, without psychotic features
  • QIDS-SR score of at least 10 (i.e., moderate depression) at initial visit
  • Failure of at least 1 prior adequate trial of a standard antidepressant (i.e., 6 weeks at adequate dose), assessed by the Antidepressant Treatment History Questionnaire (ATRQ)18 criteria
  • Inpatient and expected to remain so for 5 or more days
  • Hospitalized within past 72 hours

Exclusion Criteria:

  • Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy). Immediately after the pregnancy test, women with positive pregnancy tests will be unable to enroll in the study
  • Women who are breastfeeding
  • Patients who have taken an investigational psychotropic drug within the last 3 months
  • Section 12 status (involuntary admission)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01555021

Contacts
Contact: John D Matthews, MD 6177249144 jmatthews@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: John D Matthews, MD    617-724-9144    jmatthews@partners.org   
Principal Investigator: John D Matthews, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: John D Matthews, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: John D. Matthews, Director of Research and Training, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01555021     History of Changes
Other Study ID Numbers: 2011-P-001921
Study First Received: February 16, 2012
Last Updated: November 14, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014