Abstinence from Alcohol for Alcoholism

(SPAR Trial)

Overseen By Ann E Kosobud, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Indiana University

Must not be taking: Antidepressants, Antipsychotics, Benzodiazepines

Disqualifiers: Pregnancy, Substance use disorder, Neurological disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how abstaining from alcohol affects drinking habits differently in men and women. Participants will either abstain from alcohol or maintain their usual drinking routines. Researchers aim to determine if these patterns can enhance prevention or intervention strategies for alcohol-related issues. This trial suits moderate social drinkers who can complete questionnaires in English and have a suitable BMI.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that participants not take certain medications that could affect the study or their safety, such as antidepressants, antipsychotics, and benzodiazepines, within the past 30 days. You may need to stop taking these medications before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abstaining from alcohol is generally safe. No direct evidence suggests that not drinking causes harm or negative effects. Avoiding alcohol is a common component of many treatments for alcohol use disorder. Studies indicate that many individuals attempt to stop drinking as part of their recovery. However, for those who have been drinking heavily for an extended period, sudden cessation can lead to withdrawal symptoms. These symptoms range from mild to severe, so medical supervision is often recommended for safety. Overall, when managed properly, abstaining from alcohol is considered well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores two unique approaches for managing alcoholism: abstinence from alcohol and usual drinking, to better understand their impacts. Unlike conventional treatments like medication-assisted therapy with drugs such as naltrexone or acamprosate, which directly target brain chemistry, this trial focuses on behavioral interventions and their long-term effects. By examining how varying alcohol exposure influences behavior through tasks and EEG monitoring, researchers aim to uncover new insights into the brain's response to alcohol and potential behavioral strategies for treating alcoholism. This could lead to more personalized and effective treatment plans based on individual behavioral responses rather than a one-size-fits-all medication approach.

What evidence suggests that this trial's treatments could be effective for alcoholism?

This trial will compare abstinence from alcohol with usual drinking. Research has shown that taking a break from alcohol can lead to positive changes in drinking habits. Studies have found that people who stop drinking for a while often end up drinking less overall. Programs like Alcoholics Anonymous have also succeeded in helping people remain alcohol-free long-term. In one study, participants who stopped drinking and worked with healthcare professionals experienced more stable changes in their drinking patterns. This suggests that abstaining from alcohol can effectively reduce alcohol use, especially when combined with support systems. ^{3 4 6 7 8}

Who Is on the Research Team?

Martin H Plawecki, MD, PhD

Principal Investigator

Psychiatry, Indiana University School of Medicine

Melissa A Cyders, PhD

Principal Investigator

Psychology, Indiana University-Purdue University at Indianapolis

Are You a Good Fit for This Trial?

This trial is for moderate social drinkers with a BMI between 18.5 and 32 kg/m2 who can understand English. It's not for those with certain mental disorders, history of severe head injury, suicidal tendencies, pregnant or breastfeeding women, people on medications like antidepressants that could affect the study, or anyone court-ordered to abstain from alcohol.

Inclusion Criteria

I can understand and fill out questionnaires in English.

Your body mass index (BMI) falls between 18.5 and 32 kg/m2.

You drink alcohol moderately.

Exclusion Criteria

Positive breath alcohol reading on arrival at any study visit

I have a mental disorder or a brain disease, or I've had a head injury with significant unconsciousness.

You have attempted suicide in the past year, have a current plan for suicide, or are considered at high risk for suicide by the study doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Abstinence

Participants undergo 2 weeks of abstinence from alcohol to assess subjective and physiological responses

2 weeks

2 single day laboratory sessions

Experimental

Participants engage in free-access alcohol self-administration and clamped alcohol exposure sessions to study sex differences in response to alcohol

Single sessions

Multiple laboratory sessions

Follow-up

Participants are monitored for changes in alcohol consumption patterns every 2 months for 2 years

2 years

Surveys every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• Abstinence from alcohol
• Usual drinking

Trial Overview

The study examines how men and women respond differently to not drinking alcohol compared to their usual consumption. The goal is to see if this information can help tailor better prevention and intervention strategies for alcoholism.

How Is the Trial Designed?

Group I: Free access alcohol self-administration Experimental Treatment 3 Interventions

During the 2.5-hour free-access self-administration sessions, the participant may choose to complete a task for an alcohol or water reward. Interventions include Abstinence from Alcohol and Usual Drinking

Group II: Clamped alcohol exposure Experimental Treatment 3 Interventions

A battery of behavioral tasks will be administered to participants before, and at the beginning and end of a 3 hour clamped exposure to alcohol (fixed at 80 mg/dL). EEG will be recorded throughout to assess event related potentials associated with task performance. Interventions include Abstinence from Alcohol and Usual Drinking.

Group III: 2 year followup Active Control 2 Interventions

Participants from both Arm 1 and Arm 2 will be surveyed every 2 months for alcohol consumption for 2 years following the Experimental phase. Interventions include Abstinence from Alcohol and Usual Drinking.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

This study aims to evaluate the effectiveness of baclofen in preventing restlessness-related complications in 314 patients with alcohol withdrawal syndrome who are mechanically ventilated in intensive care units, highlighting the serious risks associated with alcohol withdrawal, including delirium tremens.

The primary goal is to determine if baclofen can reduce incidents of restlessness, which can lead to dangerous situations like unplanned extubation and aggression, thereby potentially improving patient safety and outcomes in the ICU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baclofen to prevent agitation in alcohol-addicted patients in the ICU: study protocol for a randomised controlled trial. Vourc'h, M., Feuillet, F., Mahe, PJ., et al.[2018]

The review highlights the varying approaches to treating alcoholism, including total abstinence, controlled drinking, and responsible drinking, emphasizing that treatment should be tailored to the individual's severity of the problem.

The authors advocate for compulsory abstinence as an effective strategy within voluntary hospitalization and psychotherapy, supported by a clinical case that demonstrates its benefits in family therapy contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Which abstinence in alcohol problems?]. Nozeret, Y., Meire, P., Derely, M.[2006]

In a study of 21,925 current drinkers, those who reduced their WHO drinking risk levels showed significantly lower odds of developing liver disease and scoring positively on an alcohol screening measure after three years.

Specifically, very-high-risk drinkers who reduced their risk levels had odds ratios as low as 0.17 for liver disease and 0.03 for positive AUDIT-C scores, indicating that even nonabstinent drinking reductions can be clinically relevant outcomes in alcohol treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT-C Scores: Prospective 3-Year Follow-Up Results in the U.S. General Population. Knox, J., Wall, M., Witkiewitz, K., et al.[2023]

In a study of 507 patients with nonfatal acute myocardial infarction (AMI) and 478 control patients, current drinkers had a significantly lower risk of AMI compared to lifelong abstainers, with an odds ratio of 0.56.

Former drinkers also showed a reduced risk of AMI, and the protective effect of alcohol consumption may last for several years after cessation, suggesting that stopping drinking does not immediately eliminate the protective benefits against AMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk of acute myocardial infarction after stopping drinking. Negri, E., La Vecchia, C., Pelucchi, C., et al.[2015]

In a study analyzing data from 1,383 participants in the COMBINE study, it was found that heavy drinking and nonheavy drinking behaviors were stable over consecutive months, indicating that the outcomes of no heavy drinking can be reliably measured within the first 4 months of treatment.

Many individuals who were heavy drinkers at the start of treatment showed significant reductions in their drinking, with over two-thirds reporting a 64% decrease in frequency and a 38% decrease in intensity, suggesting that the current heavy drinking thresholds may overlook meaningful improvements in alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal Stability of Heavy Drinking Days and Drinking Reductions Among Heavy Drinkers in the COMBINE Study. Witkiewitz, K., Wilson, AD., Pearson, MR., et al.[2019]

In a study involving 1169 adults with alcohol dependence, outcomes based on WHO drinking risk level reductions were found to be more achievable and clinically meaningful compared to total abstinence or no heavy drinking days, suggesting they may better reflect patient goals.

The results indicated that while total abstinence was the least achieved outcome, WHO 1-level and 2-level reductions showed higher response rates, making them valuable indicators for evaluating the effectiveness of pharmacotherapy in treating alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials. Falk, DE., O'Malley, SS., Witkiewitz, K., et al.[2022]

Harm-reduction programs, originally designed for illicit drug use, can effectively be adapted for alcohol prevention by reducing the negative consequences of intoxication, such as injuries during fights.

These approaches may be more efficient as they target heavy-drinking occasions, which are more closely linked to drinking problems than overall alcohol consumption levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harm Reduction as an Alcohol-Prevention Strategy. Single, E.[2020]

In a study involving young adult male rhesus macaques over 26 months, it was found that involuntary abstinence from alcohol can lead to increased drinking levels, especially in heavy drinkers, even without clear physical withdrawal symptoms.

The research indicated that heavy drinkers maintained significantly higher alcohol intake (1.0-2.6 g/kg) for over three months after abstinence, while non-heavy drinkers returned to baseline levels within three months, highlighting the different biological responses to abstinence based on drinking history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of repeated abstinence on chronic ethanol self-administration in the rhesus monkey. Allen, DC., Gonzales, SW., Grant, KA.[2020]

The lack of standardized definitions for abstinent and non-abstinent outcomes in alcoholism treatment studies leads to significant discrepancies in reported success rates.

A proposed definitional scheme aims to create consensus on these outcomes, which could help clarify the effectiveness of different treatment approaches for alcoholism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitions of non-abstinent and abstinent categories in alcoholism treatment outcome classifications: a review and proposal. Heather, N., Tebbutt, J.[2019]

Recent research indicates that traditional views on alcoholism treatment, which emphasize complete abstinence as the only path to rehabilitation, may not be the most effective approach for overall improvement in health and well-being.

Nonabstinent treatment programs are emerging as viable alternatives, suggesting that controlled or attenuated drinking may also lead to positive outcomes in emotional, interpersonal, and physical health for individuals with alcohol use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonabstinent drinking goals in the treatment of alcoholism. A clinical typology. Pattison, EM.[2019]

In a study of 297 adolescents aged 13-18 with ADHD and comorbid substance use disorder, only 15% achieved a significant 2-level reduction in WHO drinking risk level during a 16-week treatment, highlighting the variability in treatment response.

Achieving at least a 2-level reduction in drinking risk was linked to greater improvements in ADHD symptoms and overall functioning, suggesting that this measure could be a valid treatment outcome for youth with alcohol use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are non-abstinent reductions in World Health Organization drinking risk level a valid treatment target for alcohol use disorders in adolescents with ADHD? Mitchell, HM., Park, G., Hammond, CJ.[2022]

German guidelines for treating alcohol dependence focus solely on abstinence as the treatment goal, while international guidelines allow for alcohol reduction as an intermediate goal if abstinence is not immediately achievable.

Incorporating patients' preferences in treatment goals, including the option for reducing alcohol consumption, can lead to better health outcomes and should be considered in German treatment recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment recommendations for alcohol dependence--comparison of German and international guidelines]. Spyra, A., Rychlik, RP.[2013]

In a study of 964 participants from the COMBINE trial, reducing WHO risk drinking levels by 2 or more levels during treatment led to a significant 52% decrease in healthcare costs in the year following treatment and a 44% decrease over 3 years.

These cost reductions were primarily due to lower use of inpatient behavioral health services and emergency department visits, highlighting the economic benefits of achieving drinking reductions in individuals with alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Relationship Between Reductions in WHO Risk Drinking Levels During Treatment and Subsequent Healthcare Costs for the ACTIVE Workgroup. Aldridge, AP., Zarkin, GA., Dowd, WN., et al.[2023]

Abstinence is traditionally seen as the best goal for treating alcohol disorders, but recent studies suggest that focusing on reducing heavy drinking can also be a valuable outcome, as it reflects real progress for patients.

Recognizing reductions in alcohol consumption, rather than just abstinence, can provide a clearer understanding of treatment effectiveness and its public health implications, encouraging a more personalized approach to treatment goals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in heavy drinking as a treatment outcome in alcohol dependence. Gastfriend, DR., Garbutt, JC., Pettinati, HM., et al.[2019]

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