Ignite Creation Date:
2024-05-06 @ 1:01 PM
Last Modification Date:
2024-10-26 @ 1:07 PM
Study NCT ID:
NCT03907124
Status:
WITHDRAWN
Last Update Posted:
2023-09-21
First Post:
2019-03-12
Brief Title:
Clinical Utility of Pharmacogenomics of Psychotropic Medications
Sponsor:
Oregon Health and Science University
Organization:
Oregon Health and Science University
Study Overview
Official Title:
Clinical Utility of Pharmacogenomics of Psychotropic Medications
Status:
WITHDRAWN
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
PI left institution prior to recruitment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
There is considerable inter-individual variability in therapeutic drug response required dosage and adverse effects in psychotropic treatment Few patients experience a remission of their illness when initially treated with any medications12 In those who remain symptomatic less than half will experience a significant improvement with a change in medication or with the addition of an alternative psychotropic medication2 Variation in drug response is complex and is dependent on a number of factors including diagnostic accuracy the potential for drug-drug interactions age gender renal and hepatic functioning medical and psychiatric comorbidity nutritional status coincident substance use genomic and related downstream translational factors and patient compliance In recent studies examining the use of antidepressants antipsychotics mood stabilizers and pain medications substantial proportions of study patients discontinue treatment as a consequence of adverse effects or symptom relapse3-5 Similarly in community practice settings nearly half of the patients make no follow-up visits and only a fourth return to pursue regular primary treatment67 Prolonged times to response whether caused by adverse effects or by other factors are associated with substantial increased risk for morbidity or mortality Pharmacogenomic testing is expected to improve response as well as minimize the likelihood of adverse effects associated with patient nonadherence and extended morbidity8-10 While the scientific understanding of pharmacogenomics is quickly accelerating its translation to clinical decision-making in practice has progressed more slowly1112 In an effort to begin to bridge this translational gap a pharmacogenomicpharmacogenetic testing has been developed for various and commonly existing psychiatric disorders to improve the safety of prescribing medications This pharmacogenomic-based interpretive report is based on genotyping both copies of multiple informative genes which are 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 cytochrome P450 enzymes genes code for the enzymes that are responsible for metabolism of most antipsychotic antidepressant and pain medications The UGT2B15 is for benzodiazepine metabolism The COMT gene is for dopamine metabolism and is relevant for cognitive function depression and smoking The SLC6A4 and the 5HT2A have been associated with differential treatment response to specific medications The 5HT2C is for weight gain the ABCB1 gene is for pain some psychotropics such as risperidone the dopamine 2 D2 receptor gene for psychotropic medications weight gain and pain medications and the opioid mu OPRM1 receptor gene for weight and pain Sodium channels SCN2A gene for autism seizures and bipolar disorder GRIK4 gene is for kainite receptor involvement with rapidly acting antidepressants pain dysphoria and potentially psychotropic medications ANKK1 is for smoking weight management and bipolar disorder The MHTFR is for antidepressants D1 is for psychotropic response
Such genetic testing has a significant potential to reduce healthcare costs through increased efficacy and tolerability of antidepressant medications as well as medication adherence However there is a relative lack of such efforts with psychotropic medications APMs in the treatment of various psychiatric disorders such as schizophrenia major depression or bipolar disorder This is despite significant room for improvement in efficacy and tolerability of currently available drugs in such patients Consequently the investigators are proposing to utilize genetic testing to select more genetically-informed medications to enhance their effectiveness in real-world patients with psychiatric illnesses such as schizophrenia major depression and bipolar affective disorder as well as medical problem with chronic pain in a large state hospital setting The investigators plan to use genetic testing offered by Admera for medications The investigators hypothesize that utilizing such pharmacogenomic testing as a treatment decision support tool will demonstrate clinical benefits by improving patient response and decreasing adverse effects to the psychotropic medications The proposed study will be conducted at the Oregon State Hospital Salem Oregon over a total period of 12 months
The cytochrome P450 enzymes genes code for the enzymes that are responsible for metabolism of most antipsychotic antidepressant and pain medications The UGT2B15 is for benzodiazepine metabolism The COMT gene is for dopamine metabolism and is relevant for cognitive function depression and smoking The SLC6A4 and the 5HT2A have been associated with differential treatment response to specific medications The 5HT2C is for weight gain the ABCB1 gene is for pain some psychotropics such as risperidone the dopamine 2 D2 receptor gene for psychotropic medications weight gain and pain medications and the opioid mu OPRM1 receptor gene for weight and pain Sodium channels SCN2A gene for autism seizures and bipolar disorder GRIK4 gene is for kainite receptor involvement with rapidly acting antidepressants pain dysphoria and potentially psychotropic medications ANKK1 is for smoking weight management and bipolar disorder The MHTFR is for antidepressants D1 is for psychotropic response
Such genetic testing has a significant potential to reduce healthcare costs through increased efficacy and tolerability of antidepressant medications as well as medication adherence However there is a relative lack of such efforts with psychotropic medications APMs in the treatment of various psychiatric disorders such as schizophrenia major depression or bipolar disorder This is despite significant room for improvement in efficacy and tolerability of currently available drugs in such patients Consequently the investigators are proposing to utilize genetic testing to select more genetically-informed medications to enhance their effectiveness in real-world patients with psychiatric illnesses such as schizophrenia major depression and bipolar affective disorder as well as medical problem with chronic pain in a large state hospital setting The investigators plan to use genetic testing offered by Admera for medications The investigators hypothesize that utilizing such pharmacogenomic testing as a treatment decision support tool will demonstrate clinical benefits by improving patient response and decreasing adverse effects to the psychotropic medications The proposed study will be conducted at the Oregon State Hospital Salem Oregon over a total period of 12 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None