ALDH2 Genetic Testing in East Asian Community

Official title

A Community-Based Approach for ALDH2 Genetic Testing in East Asian Americans

Overview

The goal of this clinical trial is to learn whether education plus genetic testing for ALDH2\*2 and ADH1B\*2 is feasible and acceptable and whether it influences modifiable health behaviors in East Asian American adults who experience alcohol flushing when they drink alcohol or have a family history of flushing. The main questions it aims to answer are: 1. Is providing education plus ALDH2\*2/ADH1B\*2 genetic testing feasible and acceptable in a clinical care context? 2. Does receiving genetic testing results plus education lead to changes in modifiable health behaviors compared with education alone? Researchers will compare education plus genetic testing (intervention arm) to education only (control arm) to see if adding genetic testing improves feasibility/acceptability and supports health behavior change. Participants will: 1. Complete an education module about alcohol flushing and ALDH2/ADH1B 2. Be randomized to either: (A) Receive genetic testing for ALDH2\*2 and ADH1B\*2 with results disclosure, or (B) Receive education only. 3. Complete follow-up measures about feasibility, acceptability, and modifiable health behaviors

Detailed description

Alcohol flushing syndrome affects an estimated \>500 million individuals worldwide and is strongly associated with functional variants in alcohol metabolism genes, particularly ALDH2 (e.g., ALDH2\*2) and ADH1B (e.g., ADH1B\*2). ALDH2\*2 reduces aldehyde dehydrogenase activity, contributing to acetaldehyde accumulation and is associated with increased risk for alcohol-related morbidity, including certain cancers and cardiometabolic outcomes. Despite the public health relevance, ALDH2/ADH1B implementation in clinical care remains limited, and evidence-based strategies are needed to support equitable and ethical adoption, especially for populations underrepresented in genomics research. This study will engage the East Asian American community to evaluate implementation strategies for ALDH2\*2 and ADH1B\*2 genetic testing and education in clinical settings and to examine the behavioral impact of returning genetic risk information. Using a pragmatic, randomized comparative effectiveness pilot design, East Asian American adults who self-report alcohol flushing and/or a family history of flushing will be randomized to either: (1) education plus ALDH2\*2/ADH1B\*2 genetic testing with genotype-informed result disclosure, or (2) education alone. Primary outcomes are feasibility and acceptability of the testing-and-education approach; secondary outcomes include changes in modifiable health behaviors (e.g., alcohol-related decision-making) following education with or without genetic result return. Findings will inform scalable implementation pathways and contribute to equitable integration of genomic testing into routine care for populations experiencing healthcare disparities.

Interventions

• Behavioral Genetic Test Results Return
  Returning genetic test results for alcohol flushing genes (i.e., ALDH2, ADH1B)
• Behavioral Alcohol Flushing Education
  Administering alcohol flushing educational module.

Primary outcome measures

• Feasibility of Alcohol Flushing Genetic Testing in Primary Care [Time frame: From enrollment to the end of data collection at 8 weeks.]

Secondary outcome measures (2)

• Acceptability of Alcohol Flushing Genetic Testing in Primary Care [Time frame: From enrollment to the end of data collection at 8 weeks.]
• Change(s) in Alcohol Consumption [Time frame: Alcohol consumption outcome measurements at baseline and one month after educational modules are shared AND after genetic testing results are received.]

Eligibility criteria

Inclusion criteria

• Age 18 or older
• Self-identified as East Asian and/or East Asian American
• Flush when they drink alcohol or have a family member who flushes when they drink
• Able to read and speak English

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Northwestern University Feinberg School of Medicine — Chicago

Publications

• Zhang LL, Wang YQ, Fu B, Zhao SL, Kui Y. Aldehyde dehydrogenase 2 (ALDH2) polymorphism gene and coronary artery disease risk: a meta-analysis. Genet Mol Res. 2015 Dec 28;14(4):18503-14. doi: 10.4238/2015.December.23.38. PMID 26782498
• Yasue H, Mizuno Y, Harada E. Association of East Asian Variant Aldehyde Dehydrogenase 2 Genotype (ALDH2*2*) with Coronary Spasm and Acute Myocardial Infarction. Adv Exp Med Biol. 2019;1193:121-134. doi: 10.1007/978-981-13-6260-6_7. PMID 31368101
• Xu YL, Hu YY, Li JW, Zhou L, Li L, Niu YM. Aldehyde dehydrogenase 2 rs671G>A polymorphism and ischemic stroke risk in Chinese population: a meta-analysis. Neuropsychiatr Dis Treat. 2019 Apr 23;15:1015-1029. doi: 10.2147/NDT.S196175. eCollection 2019. PMID 31114208
• Ding JH, Li SP, Cao HX, Wu JZ, Gao CM, Liu YT, Zhou JN, Chang J, Yao GH. Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population. J Hum Genet. 2010 Feb;55(2):97-102. doi: 10.1038/jhg.2009.129. Epub 2009 Dec 11. PMID 20010786
• Chen J, Huang W, Cheng CH, Zhou L, Jiang GB, Hu YY. Association Between Aldehyde dehydrogenase-2 Polymorphisms and Risk of Alzheimer's Disease and Parkinson's Disease: A Meta-Analysis Based on 5,315 Individuals. Front Neurol. 2019 Mar 28;10:290. doi: 10.3389/fneur.2019.00290. eCollection 2019. PMID 30984100

Identifiers

NCT: NCT07392775 · STU00222224 · 1K01HL173859-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗