Department of Health
and Human Services (HHS)
and Human Services (HHS)
May 24, 2021
None
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
This notice announces the availability of DNA and RNA samples collected from an National Institute on Alcohol Abuse and Alcoholism (NIAAA)-sponsored multi-site clinical trial of gabapentin enacarbil extended-release (GE-XR, HORIZANT) for the treatment of alcohol use disorder (AUD). These samples can be used to extract and analyze genomic, epigenomic, and transcriptomic data. The goal of NIAAA is to advance precision medicine by discovering pharmacogenomic, pharmacoepigenomic, and pharmacotranscriptomic predictors of individual differences to AUD treatment. Investigators interested in obtaining NIAAA samples should contact Dr. Dan Falk (see below).
Program Information:
A NIAAA Medications Development contract supported a large multi-site phase 2 clinical trial of GE-XR between June 2015 and February 2017. Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites.1 Individuals received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention for 6 months. The results did not show a difference in alcohol consumption or craving between GE-XR and placebo groups. However, because of the heterogeneity of AUD, we may be able to identify subgroups that responded favorably to GE-XR. In the GE-XR trial, blood samples for DNA genotyping and RNA expression analyses were collected from 346 participants and stored at -70 C. The phenotypic and outcome data set of the GE-XT trial is now available through a data transfer agreement that can be obtained through NIAAA at the following url:
https://www.niaaa.nih.gov/horizantr-gabapentin-enacarbil-extended-release-study
Researchers are encouraged to link the phenotypic and outcome data with the DNA and RNA biomarkers. Further analysis of the DNA and RNA samples might provide information on the responders to GE-XR. Recently, using the public data set of the GE-XR trial, subgroups were identified that responded to GE-XR based on a machine learning model of patient characteristics and self-reports.2
DNA and RNA Collection and Storage
Blood samples for DNA genotyping and RNA expression were collected from 348 subjects using standard phlebotomy techniques into PAXgene tubes. These tubes contain a special preservative to stabilize DNA and RNA in the sample until extraction can occur. DNA samples were collected at randomization and RNA samples were collected at randomization and at the end of treatment at week 24. During the collection period, two 8.5 ml of blood were collected in DNA tubes and two 2.5 ml of blood were collected for RNA. The samples were then stored at -70 oC. Researchers interested in using the DNA and RNA samples would need to perform the appropriate DNA genotyping and RNA expression to extract relevant data.
1Falk DE, Ryan ML, Fertig FB, Devine EG, Cruz E, et al (2019) Gabapentin enacarbil extended-release for alcohol use disorder: A randomized, double-blind, placebo-controlled, multisite trial assessing efficacy and safety. Alcohol Clin Exp Res 43: 158-169.
2Laska EM, Siegel CE, Lin Z, Bogenschutz M, Marmar CR (2020) Gabapentin enacarbil extended-release versus placebo: A likely responder reanalysis of a randomized clinical trial. Alcohol Clin Exp Res 44: 1875-1884.
Daniel Falk, Ph.D.
Medications Development Branch
Division of Treatment and Recovery
National Institute on Alcohol Abuse and Alcoholism(NIAAA)
Telephone: 301-443-0788
Email: falkde@mail.nih.gov