Clinical trial NCT02189057: A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management Of Depression
Official title: A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management of Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Mood Disorder
Bipolar
Keywords: Bipolar
Unipolar
Genotyping
Pharmacokinetic
Pharmacodynamic
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2014-07-14
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Subjects will be randomized to either genotyping intervention or treatment as usual.
Primary purpose: TREATMENT

Brief summary: The overall goal of this investigator-initiated trial is to evaluate the treatment outcome of depression utilizing platform algorithm products that can allow rapid identification of pharmacokinetic (PK) and/or pharmacodynamic (PD) genomic variation. This new technology may have the potential to optimize treatment selection by improving response, minimizing unfavorable adverse events / side effects and increasing treatment adherence.

Detailed description: Treatment seeking depressed patients (SCID confirmed major depressive disorder or bipolar I/II disorder) to the Mayo Clinic Depression Center will be invited to participate in this study evaluating the Assurex GeneSight® platform; this new technology can rapidly assess PK and PD genetic variation that can potentially impact antidepressant, antipsychotic, and stimulant associated treatment outcomes for depression. This study will recruit treatment seeking patients with major depression with an index episode of moderate symptom severity that has been unresponsive or poorly tolerated to at least one prior antidepressant treatment. This will be an 8-week, double-blind trial where depressed patients are randomized to testing results of GeneSight® (tricolored clinical report) prior to treatment selection (n=138) vs. treatment as usual (tricolored dummy report) (n=138). All testing results will be made available after the 8-week trial.

Eligibility criteria: Inclusion Criteria:

1. Age 18-65, male or female, any race/ethnicity
2. Mayo Clinic Depression Center inpatient or outpatient, or an outpatient of Mayo Clinic Rochester and satellite clinics, and outpatients from Mayo Clinic Health System clinics
3. Ability to provide informed consent
4. Structured Clinical Interview (SCID) confirmed major depressive episode associated with Major Depressive Disorder, Bipolar I/II disorder, or Schizoaffective Bipolar Disorder
5. Current index episode of major depression \< 2 years duration
6. Moderate symptom severity defined by HAMD-17 rating scale score ≥ 17 \[8\]
7. Current index episode having not been treated with psychotropic medications or inadequately responsive to treatment (IRT). IRT defined as intolerability, adverse event, or inadequate efficacy of current psychotropic medication (at least 4 weeks duration)
8. 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
9. Negative serum or urine pregnancy test (or history of hysterectomy)
10. Negative urine toxicology test (will only be completed at the request of the treating clinician).

Exclusion Criteria:

1. Inability to speak English
2. Inability or lack of willingness to provide informed consent
3. Axis I or II disorder other than depression (i.e., by clinical assessment) that is the primary reason for treatment
4. Psychotropic medication change (including dosage) between screening \& baseline visit with exception of no more than 8mg of Ativan within a 24-hour period.
5. Patients who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for any significant current substance use disorder other than nicotine or caffeine. Must have at least early, partial or full, remission X 3 months
6. Clinically diagnosed cannabis use disorder, or SCID confirmed cannabis abuse or dependence.
7. Current clinical diagnosis delirium, dementia, other cognitive disorders, or non-mood psychotic disorder (i.e., schizophrenia, delusional disorder)
8. Index episode symptoms of hallucinations or delusions
9. Serious suicidal risk and/or in need of immediate hospitalization as judged by the investigator
10. History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months
11. Significant unstable medical condition
12. Hepatic insufficiency (2.5 X upper limit of normal (ULN) for Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ), past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver
13. 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
14. Participation in another clinical trial within 30 days of the screening visit
15. Anticipated inability to attend scheduled study visits
16. Patients who in the judgment of the Investigator may be unreliable or uncooperative with the evaluation procedure outlined in this protocol
17. Known cytochrome (CYP) \& serotonin transporter genomic testing results within 5 years
18. A score of ≥15 on the Young Mania Rating Scale (YMRS)

Primary outcomes:
measure: Change in depression as measured by the Quick Inventory of Depressive Symptoms (QIDS-C16)
timeFrame: baseline, 8 weeks
Secondary outcomes:
measure: Number of subjects with improvement of depressive symptoms as shown by 50% reduction in QIDS-C16 score
timeFrame: 8 weeks
measure: Number of subjects with improvement of depressive symptoms as shown by a score <6 on QIDS-C16
timeFrame: 8 weeks
measure: Number of subjects with improvement of depressive symptoms as shown by score of "much" or "very much improved" on Clinical Global Impression - Improvement Scale
timeFrame: 8 weeks
measure: Improvement of depressive symptoms as shown by the Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: 8 weeks
measure: Improvement of depressive symptoms
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Mark Frye, MD
role: PRINCIPAL_INVESTIGATOR
References: