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| ID | Type | Description | Link |
|---|---|---|---|
| P20-acam |
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| Name | Class |
|---|---|
| Samuel C. Johnson Foundation | UNKNOWN |
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In 2004, acamprosate was approved in the U.S. for abstinence maintenance, by decreasing craving, in alcoholic patients who have undergone detoxification. while a new anti-craving drug was encouraging, only 36.1% of the subjects treated with acamprosate remained abstinent for 6 months. Having the ability to identify treatment responsive individuals would have a major impact on the use of acamprosate.
The primary objective of this pharmacogenomic probe study of acamprosate is to identify genetic variations that predict response. Our hypothesis is that effective acamprosate response in alcohol dependent subjects may be influenced by genetically controlled variation in the functionality of the N-methyl-D-aspartate receptor (NMDA) and/or the type 5 metabotropic glutamate receptor (mGluR5). Hypothesis confirmation could lead to development of effective individualized treatment recommendations for alcohol dependent patients based on pharmacogenomically relevant genetic variations.
The general goal is to identify genetic polymorphic variants that differentiate subjects continuously abstinent for six months while taking acamprosate from relapsed subjects. The initial analysis will determine whether any of ten polymorphisms in four target genes (GRIN1, GRIN2A and GRIN2B that code for the NMDA receptor and GRM5 that codes for the type mGluR5 receptor) are associated with successful abstinence. Subsequent analyses will examine whether variation in a comprehensive set of 383 linkage disequilibrium haplotype tagged single nucleotide polymorphisms of these four genes predicts successfully abstinent subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Our hypothesis is that effective acamprosate response in alcohol dependent subjects may be influenced by genetically controlled variation in the functionality of the N-methyl-D-aspartate receptor (NMDA) and/or the type 5 metabotropic glutamate receptor (mGluR5). Hypothesis confirmation could lead to development of effective individualized treatment recommendations for alcohol dependent patients based on pharmacogenomically relevant genetic variations. There will be no placebo drug given. Just measurement of genetic response. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| acamprosate | Drug | acamprosate 333mg tabs, 2tabs 3times per day = 1998mg/day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Aim 1: To determine the relationship between genetically determined variation in the NMDA receptor and treatment response to acamprosate. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Aim 2: To determine the relationship between genetically determined variation in the mGluR5 receptor and treatment response to acamprosate. | 6months |
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Inclusion Criteria:
Exclusion Criteria:
9. Active suicidal ideation as determined by responses provided during PRISM or as determined by the investigator.
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Subjects selected from Mayo Clinics Addiction programs.
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| Name | Affiliation | Role |
|---|---|---|
| David Mrazek, M.D. | Mayo Clinic, Department of Psychiatry | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38852760 | Derived | Ho MF, Zhang C, Cohan JS, Tuncturk M, Heider RM, Coombes BJ, Biernacka J, Moon I, Skime M, Ho AM, Ngo Q, Skillon C, Croarkin PE, Oesterle TS, Karpyak VM, Li H, Weinshilboum RM. IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study. Brain Behav Immun. 2024 Aug;120:304-314. doi: 10.1016/j.bbi.2024.06.007. Epub 2024 Jun 8. | |
| 37689244 |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077443 | Acamprosate |
| ID | Term |
|---|---|
| D013654 | Taurine |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
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Samples obtained from study "Developing a DNA Repository for Genomic Studies of Addiction: A Pilot Study"
| Derived |
| Ho MF, Zhang C, Moon I, Biernacka J, Coombes B, Ngo Q, Skillon C, Skime M, Oesterle T, Croarkin PE, Karpyak VM, Li H, Weinshilboum RM. Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation. Mol Metab. 2023 Nov;77:101798. doi: 10.1016/j.molmet.2023.101798. Epub 2023 Sep 7. |
| 36608483 | Derived | Karpyak VM, Coombes BJ, Geske JR, Pazdernik VM, Schneekloth T, Kolla BP, Oesterle T, Loukianova LL, Skime MK, Ho AM, Ngo Q, Skillon C, Ho MF, Weinshilboum R, Biernacka JM. Genetic predisposition to major depressive disorder differentially impacts alcohol consumption and high-risk drinking situations in men and women with alcohol use disorder. Drug Alcohol Depend. 2023 Feb 1;243:109753. doi: 10.1016/j.drugalcdep.2022.109753. Epub 2022 Dec 24. |
| 35752286 | Derived | Ho MF, Zhang C, Moon I, Wei L, Coombes B, Biernacka J, Skime M, Choi DS, Frye M, Schmidt K, Gliske K, Braughton J, Ngo Q, Skillon C, Seppala M, Oesterle T, Karpyak V, Li H, Weinshilboum R. Genome-wide association study for circulating FGF21 in patients with alcohol use disorder: Molecular links between the SNHG16 locus and catecholamine metabolism. Mol Metab. 2022 Sep;63:101534. doi: 10.1016/j.molmet.2022.101534. Epub 2022 Jun 22. |
| 27009547 | Derived | Karpyak VM, Biernacka JM, Geske JR, Abulseoud OA, Brunner MD, Chauhan M, Hall-Flavin DK, Lewis KA, Loukianova LL, Melnyk GJ, Onsrud DA, Proctor BD, Schneekloth TD, Skime MK, Wittkopp JE, Frye MA, Mrazek DA. Gender-specific effects of comorbid depression and anxiety on the propensity to drink in negative emotional states. Addiction. 2016 Aug;111(8):1366-75. doi: 10.1111/add.13386. Epub 2016 May 5. |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |