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| ID | Type | Description | Link |
|---|---|---|---|
| 1R34AA032300-01A1 | U.S. NIH Grant/Contract | View source |
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This study tests whether providing financial rewards based on a blood test result can help people with alcohol-associated liver disease (ALD) stop or reduce their drinking. The blood test is called phosphatidylethanol (PEth), which can detect alcohol use over the past three to four weeks. The financial reward program is called contingency management (CM).
The study has two parts. Part 1 involves one-time interviews and surveys with patients and healthcare providers to understand how a PEth-based CM program could best be delivered in a liver disease clinic. Part 2 is a pilot randomized controlled trial (the REINFORCE Trial) in which participants are randomly assigned to one of two groups: (1) a rewards group that receives escalating financial incentives when PEth results show reduced or no alcohol use, or (2) a monitoring group that receives fixed payments regardless of PEth results. Both groups receive PEth testing and continue their usual medical care. The study will assess whether the rewards program improves alcohol abstinence and reduction at 12 and 24 weeks.'
Alcohol-associated liver disease (ALD) accounts for approximately 50% of liver-related deaths in the United States and is the leading indication for liver transplantation. Despite the clear benefits of alcohol use disorder (AUD) treatment, fewer than 15% of ALD patients receive any evidence-based AUD treatment. Contingency management (CM) is one of the most effective behavioral interventions for substance use disorders, providing tangible incentives contingent on verifiable behavior change. Its application in ALD has been limited by the lack of reliable alcohol monitoring methods with sufficient detection windows.
Phosphatidylethanol (PEth) is a direct alcohol biomarker with a detection window of up to four weeks, high sensitivity, and high specificity. PEth testing can now be conducted via at-home dried blood spot (DBS) sampling, reducing burden for medically complex patients. Integrating PEth-based monitoring with CM in the hepatology clinic offers a novel strategy to improve AUD treatment engagement and promote sustained alcohol abstinence in ALD patients.
Aim 1 (Months 1-9): A mixed-methods formative study enrolling 15 ALD patients and 15 hepatology/addiction providers. Semi-structured interviews and surveys will assess feasibility, acceptability, and preferences for PEth-based CM delivery, guided by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Findings will inform the Aim 2 intervention design.
Aim 2 (Months 7-36): A pilot randomized controlled trial (REINFORCE Trial) enrolling 90 participants with ALD and AUD (45 per arm), randomized 1:1 stratified by AUD severity and gender. The CM arm receives escalating financial incentives based on PEth results (up to $615 over 12 weeks) and treatment engagement. The control arm receives fixed non-contingent payments on the same PEth testing schedule (up to $330 over 12 weeks). Both arms receive treatment as usual. The primary outcome is alcohol abstinence at 12 weeks (PEth <8 ng/mL). Secondary outcomes include alcohol use reduction at 12 weeks, abstinence or reduction at 24 weeks, and AUD treatment engagement. Exploratory analyses will examine treatment effect modifiers including AUD severity, liver disease stage, psychiatric comorbidities, age, and gender.'
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Contingency Management Intervention | Experimental | Participants receive a PEth based contingency management intervention designed to promote alcohol abstinence. Participants undergo serial phosphatidylethanol (PEth) testing using dried blood spot samples. Financial incentives are provided contingent on alcohol abstinence or significant reduction in alcohol use as measured by PEth levels. The intervention lasts 12 weeks with follow up through 24 weeks. |
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| PEth Monitoring Control | Active Comparator | Participants undergo the same schedule of PEth testing using dried blood spot samples but receive fixed incentives that are not contingent on alcohol use outcomes. This arm controls for monitoring and compensation while isolating the behavioral effect of contingency management. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PEth Based Contingency Management | Behavioral | Participants receive a contingency management intervention designed to promote alcohol abstinence among patients with alcohol use disorder and alcohol associated liver disease. Alcohol use is monitored using serial phosphatidylethanol (PEth) testing from dried blood spot samples. Participants receive financial incentives contingent on alcohol abstinence or substantial reduction in alcohol consumption as measured by PEth levels. Incentives escalate with consecutive negative PEth results during the 12 week intervention period. |
| Measure | Description | Time Frame |
|---|---|---|
| Alcohol Abstinence Measured by PEth | Alcohol abstinence measured using phosphatidylethanol (PEth) levels obtained from dried blood spot testing. PEth is a validated biomarker of recent alcohol consumption. The primary outcome is the proportion of participants with PEth levels consistent with alcohol abstinence during the intervention period. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Alcohol Use Measured by PEth | Change in phosphatidylethanol (PEth) levels from baseline to the end of the intervention period, reflecting reduction in alcohol consumption. | Baseline to 12 weeks |
| Intervention Feasibility |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wei Zhang, MD PHD | Contact | 16177265925 | wzhang50@mgh.harvard.edu |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31314133 | Background | Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. 2020 Jan;71(1):306-333. doi: 10.1002/hep.30866. No abstract available. | |
| 29309773 | Background | Beck O, Kenan Moden N, Seferaj S, Lenk G, Helander A. Study of measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spot (DBS) samples and application of a volumetric DBS device. Clin Chim Acta. 2018 Apr;479:38-42. doi: 10.1016/j.cca.2018.01.008. Epub 2018 Jan 5. |
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Data sharing plans have not yet been finalized. Individual participant data may be shared with qualified researchers in the future following completion of the study, subject to institutional review board approval, data use agreements, and applicable privacy protections.
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This study is a two arm randomized controlled trial evaluating a phosphatidylethanol (PEth) based contingency management intervention for alcohol abstinence among patients with alcohol associated liver disease and alcohol use disorder. Participants will be randomized in a 1:1 ratio to either a contingency management intervention group or a control group receiving PEth monitoring with fixed incentives. The intervention period is 12 weeks with follow up through 24 weeks.
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This is an open label behavioral intervention study. Participants and investigators are aware of group assignment because incentives in the intervention group are contingent on PEth results.
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| PEth Monitoring with Fixed Incentives | Behavioral | Participants undergo serial phosphatidylethanol (PEth) testing using dried blood spot samples at the same schedule as the intervention group. Participants receive fixed incentives for completing testing visits, but incentives are not contingent on alcohol use outcomes. This condition controls for study participation, monitoring, and compensation while isolating the effect of contingency management. |
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Feasibility of the contingency management intervention measured by recruitment rate, intervention completion rate, and adherence to scheduled PEth testing visits.
| 12 weeks |
| Participant Acceptability of the Intervention | Acceptability of the contingency management intervention assessed using participant satisfaction surveys and retention in the intervention. | 12 weeks |
| Sustained Alcohol Abstinence After Intervention | Proportion of participants maintaining alcohol abstinence measured by PEth after completion of the intervention. | 24 weeks |
| 37230168 | Background | Edelman EJ, Dziura J, Deng Y, DePhilippis D, Fucito LM, Ferguson T, Bedimo R, Brown S, Marconi VC, Goetz MB, Rodriguez-Barradas MC, Simberkoff MS, Molina PE, Weintrob AC, Maisto SA, Paris M, Justice AC, Bryant KJ, Fiellin DA. Contingency management with stepped care for unhealthy alcohol use among individuals with HIV: Protocol for a randomized controlled trial. Contemp Clin Trials. 2023 Aug;131:107242. doi: 10.1016/j.cct.2023.107242. Epub 2023 May 23. |
| 28639812 | Background | Petry NM, Alessi SM, Olmstead TA, Rash CJ, Zajac K. Contingency management treatment for substance use disorders: How far has it come, and where does it need to go? Psychol Addict Behav. 2017 Dec;31(8):897-906. doi: 10.1037/adb0000287. Epub 2017 Jun 22. |
| 38849555 | Background | Lee BP, Witkiewitz K, Mellinger J, Anania FA, Bataller R, Cotter TG, Curtis B, Dasarathy S, DeMartini KS, Diamond I, Diazgranados N, DiMartini AF, Falk DE, Fernandez AC, German MN, Kamath PS, Kidwell KM, Leggio L, Litten R, Louvet A, Lucey MR, McCaul ME, Sanyal AJ, Singal AK, Sussman NL, Terrault NA, Thursz MR, Verna EC, Radaeva S, Nagy LE, Mitchell MC. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. Nat Rev Gastroenterol Hepatol. 2024 Sep;21(9):626-645. doi: 10.1038/s41575-024-00936-x. Epub 2024 Jun 7. |
| 38284925 | Background | Jett JD, Beck R, Tyutyunnyk D, Sanchez J, Weeks DL, Javors MA, Hill-Kapturczak N, Lopez-Cruzan M, Kriegel L, Ginsburg BC, Cabassa L, McDonell MG. Feasibility of a telehealth-based contingency management intervention for alcohol use disorders using the phosphatidylethanol (PEth) 16:0/18:1 alcohol biomarker: a pilot randomized trial. Am J Drug Alcohol Abuse. 2024 Mar 3;50(2):162-172. doi: 10.1080/00952990.2023.2283691. Epub 2024 Jan 29. |
| 28714726 | Background | McDonell MG, Skalisky J, Leickly E, Orr MF, McPherson S, Roll J, Hill-Kapturczak N, Javors M. Pilot investigation of a phosphatidylethanol-based contingency management intervention targeting alcohol use. Psychol Addict Behav. 2017 Aug;31(5):608-613. doi: 10.1037/adb0000293. Epub 2017 Jul 17. |
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D008104 | Liver Cirrhosis, Alcoholic |
| D064829 | Alcohol Abstinence |
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D008103 | Liver Cirrhosis |
| D004066 | Digestive System Diseases |
| D008108 | Liver Diseases, Alcoholic |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020751 | Alcohol-Induced Disorders |
| D004327 | Drinking Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000431 | Ethanol |
| ID | Term |
|---|---|
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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