SBIR-STTR Award

There is a need for a highly sensitive (> 90%) and specific (> 90%) long term biomarker to both detect and monitor individuals who are heavy users of alcohol. Monitoring short term (3-5 days) alcohol use and abuse by impaired professionals by using urine ethyl glucuronide (EtG) has been shown to be both sensitive and specific (> 90%). Recently evidence has emerged that EtG in hair may be able to detect long term abusers of alcohol with a sensitivity approaching 100%. With these results as background, this Phase I study will extract EtG from hair of patients admitted for residential treatment of alcohol use disorders at Rogers Memorial Hospital (RMH). The demographics of RMH's alcohol treatment program include impaired professionals and more than 40% of patients are women. The aim of this Phase I study is to determine whether EtG levels in hair can distinguish between heavy abusers of alcohol (n= 50) and non- drinkers (n=50) with a sensitivity and specificity of greater than 90%. Using the statistical procedure of a receiver-operating characteristic (ROC) plot we will examine the whole spectrum of sensitivities and specificities over the entire range of hair EtG values obtained. We will also investigate the effects of long- term abstinence of the alcoholic patients on their hair EtG levels by analyzing hair samples taken from them after 45 days of residential treatment. In this study feasibility of hair EtG as an alcohol long term abuse marker is defined as a test having a sensitivity and specificity of 90% or greater. If feasibility in this Phase I study is established a Phase II study will expand to include women and pregnancy, binge and college drinking, transplant recipients and the development of a commercial hair EtG test. Alcohol abuse is an illness that has monumental consequences on people's every day lives, their physical and mental health, and the economies of nations. Treatment of an illness is dependent upon an early diagnosis and the current methods of self-reporting and the diagnostic tests for alcohol that are available do not detect most instances of alcohol abuse. The hair ethyl glucuronide test may prove to have superior sensitivity, specificity and ability to detect chronic alcohol abuse than the alcohol biomarkers currently in use, and be the first of a new generation of alcohol biomarkers that have a really significant impact on the treatment of this disease.

Thesaurus Terms:
Alcoholic Beverage Consumption, Alcoholism /Alcohol Abuse, Biomarker, Diagnosis Design /Evaluation, Diagnostic Test, Glucuronide, Hair, Noninvasive Diagnosis, Substance Abuse Related Behavior Drug /Alcohol Abstinence Behavioral /Social Science Research Tag, Clinical Research, Human Subject

There currently is a real need for a long term and objective alcohol biomarker to both monitor alcohol-impaired healthcare professionals, and to aid in the selection of organ transplant recipients, particularly liver transplant recipients. We recently concluded a Phase I study that compared the presence of the direct alcohol biomarker ethyl glucuronide (EtG) in hair samples from non-drinkers to hair samples obtained from problem drinkers (hair was chosen because of its 3-month exposure window to various drugs). As an alcohol biomarker EtG distinguished the drinkers from the non-drinkers with a sensitivity of 80% and a specificity approaching 100%. To determine the utility of EtG in hair and fingernail clippings as a long-term alcohol biomarker we are proposing a Phase II study that will involve two distinct population groups. One population group will consist of college students (approximately 600) that represent a span of drinking behaviors from little or no drinking to heavy and binge drinking. From this population we will determine the dose response of alcohol consumed to the amount of EtG found in the hair and fingernails. Extent of alcohol consumption by student volunteers will be determined using the technique of timeline followback interviews. The second population group studied will consist of impaired health care professionals suffering from alcohol abuse who are entering an alcohol treatment center and who will be sequestered from alcohol during treatment. From this population we will determine the half-time of the ""washout"" rate of EtG under normal hair washing and treating conditions. Hair and fingernail samples will be obtained from the volunteers at admittance, half-way through the treatment program, and upon release from the treatment program. From these samples an average half-life of EtG in hair and fingernails will be determined and from these data an average window of detection of EtG in hair and fingernails will be extrapolated. The data obtained in this Phase II study will establish the parameters of the presence of EtG in hair and fingernail samples, and will validate the conditions by which EtG in hair and/or fingernails can be used to either monitor alcohol-impaired healthcare professionals or aid in the selection of organ transplant recipients.

Public Health Relevance:
There is an immediate need for an objective means of determining alcohol ingestion by two population groups: 1) alcohol-impaired healthcare professionals undergoing treatment while continuing to practice their profession, and 2) potential organ transplant recipients, particularly liver transplant recipients. The presence of the direct alcohol biomarker ethyl glucuronide in hair and/or fingernail clippings has considerable potential as a means of objectively monitoring alcohol ingestion by these two groups and facilitating their management.

Thesaurus Terms:
Api; Alcohol Drinking; Alcohol Abuse; Alcohol Consumption; Alcoholic; Alcohols; Analysis, Data; Assay; Bioassay; Biologic Assays; Biological Assay; Boozer; Chemical Class, Alcohol; Clinical Trials, Phase I; Clinical Trials, Phase Ii; Clinical, Transplantation, Organ; Clip; Data; Data Analyses; Dependent Drinker; Deposit; Deposition; Detection; Dose; Drugs; Early-Stage Clinical Trials; Enrollment; Etoh Drinking; Exhibits; Finger Nail; Fingernail; Glucuronides; Goals; Grafting Procedure; Grafting, Liver; Grooming; Habits; Hair; Half-Life; Half-Lifes; Health Care Professional; Health Professional; Health Profession; Healthcare Professional; Healthcare Worker; History; Impaired Health; Individual; Industry; Interview; Kinetic; Kinetics; Lead; Liver Transplant; Mapi; Medication; Methods And Techniques; Methods, Other; Modeling; Monitor; Organ Transplantation; Organ Transplants; Organ Transplants, Including Bone Marrow For Dct; Participant; Patients; Pb Element; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase 1 Clinical Trials; Phase 2 Clinical Trials; Phase I Clinical Trials; Phase I Study; Phase Ii Clinical Trials; Population; Population Group; Recording Of Previous Events; Research; Sampling; Sensitivity And Specificity; Specificity; Structure Of Nail Of Finger; Students; Techniques; Testing; Time; Timeline; Transplant Recipients; Transplantation Surgery; Transplantation Of Liver; Transplantation, Hepatic; Universities; Wisconsin; Addiction; Alcohol Abuse Therapy; Alcohol Abuse Treatment; Alcohol Ingestion; Alcohol Intake; Alcohol Monitoring; Alcohol Problem; Alcohol Product Use; Alcohol Treatment; Alcohol Use; Alcoholic Beverage Consumption; Alcoholic Drink Intake; Alcoholism Treatment; Alkaline Protease Inhibitor; Behavioral Health; Binge Alcohol Consumption; Binge Drinking; Biomarker; College Student; Drinking; Drinking Behavior; Drug/Agent; Enroll; Episodic Drinking; Ethanol Abuse; Ethanol Consumption; Ethanol Drinking; Ethanol Ingestion; Ethanol Intake; Ethanol Product Use; Ethanol Use; Etoh Use; Hazardous Alcohol Use; Heavy Metal Pb; Heavy Metal Lead; Liver Transplantation; Mass Spectrometer; Microbial Alkaline Proteinase Inhibitor; Organ Allograft; Organ Graft; Organ Xenograft; Phase 1 Study; Phase 1 Trial; Phase 2 Study; Phase 2 Trial; Phase I Trial; Phase Ii Trial; Problem Drinker; Problem Drinking; Protocol, Phase I; Protocol, Phase Ii; Public Health Relevance; Response; Study, Phase Ii; Transplant Patient; Treatment Center; Treatment Program; University Student; Uptake; Volunteer