MOD: A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management Of Depression

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT02189057

Collaborator

(none)

160

Enrollment

Location

Arms

47.6

Actual Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression Mood Disorder Bipolar	Other: AssureRx GeneSight genotyping results Other: Treatment as usual	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Subjects will be randomized to either genotyping intervention or treatment as usual.Subjects will be randomized to either genotyping intervention or treatment as usual.

Masking:

Double (Participant, Investigator)

Masking Description:

Subject and study staff will be blind to randomization.

Primary Purpose:

Treatment

Official Title:

A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management of Depression

Actual Study Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Oct 19, 2018

Actual Study Completion Date :

Oct 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GeneSight guided treatment GeneSight guided group will have their research psychiatrist make treatment recommendations based on AssureRx GeneSight genotyping results.	Other: AssureRx GeneSight genotyping results
Active Comparator: Treatment as usual group Treatment as usual group will have treatment recommendations based on clinical judgment	Other: Treatment as usual

Arm

Intervention/Treatment

Experimental: GeneSight guided treatment

GeneSight guided group will have their research psychiatrist make treatment recommendations based on AssureRx GeneSight genotyping results.

Other: AssureRx GeneSight genotyping results

Active Comparator: Treatment as usual group

Treatment as usual group will have treatment recommendations based on clinical judgment

Other: Treatment as usual

Outcome Measures

Primary Outcome Measures

Change in depression as measured by the Quick Inventory of Depressive Symptoms (QIDS-C16) [baseline, 8 weeks]
The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.

Secondary Outcome Measures

Number of subjects with improvement of depressive symptoms as shown by 50% reduction in QIDS-C16 score [8 weeks]
The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
Number of subjects with improvement of depressive symptoms as shown by a score <6 on QIDS-C16 [8 weeks]
The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.
Number of subjects with improvement of depressive symptoms as shown by score of "much" or "very much improved" on Clinical Global Impression - Improvement Scale [8 weeks]
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved, 2. Much improved, 3. Minimally improved, 4. No change, 5. Minimally worse, 6. Much worse, 7. Very much worse
Improvement of depressive symptoms as shown by the Hamilton Rating Scale for Depression (HAMD-17) [8 weeks]
The HAMD-17 is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17 score ranges from 0 (not ill) to 52 (severely ill). A negative change indicates improvement in the subject's depression/anxiety symptoms, and a positive change indicates a worsening of the subject's depression/anxiety symptoms.
Improvement of depressive symptoms [8 weeks]
Treatment adherence based on concordance vs. non-concordance of gene test results and clinical intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-65, male or female, any race/ethnicity
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
Ability to provide informed consent
Structured Clinical Interview (SCID) confirmed major depressive episode associated with Major Depressive Disorder, Bipolar I/II disorder, or Schizoaffective Bipolar Disorder
Current index episode of major depression < 2 years duration
Moderate symptom severity defined by HAMD-17 rating scale score ≥ 17 [8]
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)
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
Negative serum or urine pregnancy test (or history of hysterectomy)
Negative urine toxicology test (will only be completed at the request of the treating clinician).

Exclusion Criteria:

Inability to speak English
Inability or lack of willingness to provide informed consent
Axis I or II disorder other than depression (i.e., by clinical assessment) that is the primary reason for treatment
Psychotropic medication change (including dosage) between screening & baseline visit with exception of no more than 8mg of Ativan within a 24-hour period.
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
Clinically diagnosed cannabis use disorder, or SCID confirmed cannabis abuse or dependence.
Current clinical diagnosis delirium, dementia, other cognitive disorders, or non-mood psychotic disorder (i.e., schizophrenia, delusional disorder)
Index episode symptoms of hallucinations or delusions
Serious suicidal risk and/or in need of immediate hospitalization as judged by the investigator
History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months
Significant unstable medical condition
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
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
Known cytochrome (CYP) & serotonin transporter genomic testing results within 5 years
A score of ≥15 on the Young Mania Rating Scale (YMRS)