Clinical Research Directory

Chicago Social Drinking Project

This study attempts to elucidate the factors that contribute to escalation and maintenance of excessive ethanol drinking in young adults by: 1. Examining subjective and objective response differences to alcohol and other common substances in a sample of adults with varying consumption patterns. 2. Determining whether response to alcohol and other substances is predictive of future consumption patterns through longitudinal follow-up interviews. 3. Examining the relationship between responses to alcohol and other substances at baseline and re-examination testing to evaluate if consumption patterns moderate this relationship.

SMART-r: Substance Monitoring and Active Relapse Tracking Repository

Background: About 1.5 million adults in the US enter alcohol or substance use treatment programs each year. Unfortunately, more than half of patients do not finish their program. For those who start treatment, about 70% return to substance use within weeks or months after starting treatment. To discover why patients drop out of treatment and return to substance use - and what can be done about it - researchers need to learn more about people who use drugs and alcohol. Objective: To create a data repository by gathering survey and smartphone data from adults who use drugs and alcohol in order to conduct future research. Eligibility: Adults who have used drugs or alcohol in the past and have a Android smartphone. The researchers will recruit targeted demographics at different times throughout the duration of the study period. Design: Data will be collected for up to 6 months. All research activities will be online. Participants will download a smartphone app called TTRU-Curtis AWARE and keep it active on their phone. The app will run in the background and collect participant data, including: screen unlocks, duration of time the screen is on; apps used; words typed (except passwords); duration and time of phone calls; estimated location (exact location is not collected); and movement, such as how many steps are taken in a day. All personally identifying information is automatically removed before the data is stored (including phone numbers, names, or locations described in messages). Each day, participants will receive a text with a link to a survey. They will answer questions about their mood, behavior, and substance use from the day before. This survey should take less than 5 minutes to complete. Every 30 days, participants will complete a longer survey. They will answer questions about their personal relationships, risky behaviors, mood, substance use, and feelings. They can skip any questions they do not feel comfortable answering. These surveys should take about 30 minutes to complete. Participants may opt to allow researchers to access their social media posts.

Characterization Imaging Instruments in Alcoholics and Non-Alcoholics

Background: \- People with alcoholism have differences in their brains compared with healthy people. People who are dependent on alcohol also perform differently on behavioral tasks. Researchers want to find out more about these differences. They also want to see if these differences are related to DNA. Objective: \- To see if differences in brain structure relate to personality and behavior differences in people with and without alcohol dependence. Eligibility: \- Adults age 18 and older. Design: * Participants will visit the NIH Clinical Center once during the study. * Participants will be screened with a medical history, EKG, and physical exam. They will give blood and urine samples and undergo a psychiatric interview. * Participants will be asked about their alcohol drinking, to see if they have an alcohol use disorder. * Participants will play three computerized games. Some will play these games inside a magnetic resonance imaging (MRI) scanner. * MRI: strong magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides in and out of a cylinder. They will be in the scanner for about 90 minutes. They may lie still for up to 20 minutes at a time. The scanner makes loud knocking noises. They will get earplugs.

Safety and Effectiveness of the BrainsWay Deep Transcranial Magnetic Stimulation (Deep TMS) for Treatment of Alcohol Use Disorder (AUD)

The study will compare alcohol use in two groups of subjects. One group will be assigned to the Deep TMS treatment and the other group will be assigned to the sham treatment. This is a prospective, 6-month, double blind, randomized, controlled, multi-center trial in outpatients recruited in both academic and private research centers. The study population will consist of subjects diagnosed with moderate to severe AUD. The study is comprised of three phases: 1. Pre-study Screening and Baseline Phase 2. Acute Treatment Phase and 3. Maintenance Treatment and Follow up Phase Subjects of all ethnic and gender categories, ages ranging between 18-86 years will be screened for study eligibility according to the inclusion and exclusion criteria. Subjects who meet the eligibility criteria and are willing to sign an informed consent form will be enrolled in the study. The subjects' demographic and baseline characteristics, as well as their overall medical condition will be assessed prior to treatment administration. Eligible patients will be randomized with a 1:1 ratio to one of two study groups (treatment or sham) and stratified by site. Randomization will be employed to avoid bias in the assignment of subjects to treatment group. All subjects will undergo the same treatment regimen, regardless of the assigned treatment group. The acute treatment phase will include 15 treatment visits over a period of 3-5 weeks. The Maintenance Treatment \& Follow-up phase will include one treatment visit per week from the end of the Acute Treatment Phase until the 6 month follow-up visit. At each treatment session, prior to stimulation onset, alcohol related cues will be presented to the subject. After the offset of the alcohol cue presentation, active or sham Deep TMS stimulation will be administered. The study design is directed towards a comparison between active treatment and sham, up to 4 months and 6 months follow-up. Efficacy will be assessed using the primary efficacy measure of the percent heavy drinking days during months 2-4, based on the Time Line Follow Back (TLFB) reporting. Additionally, several subject assessment scales will be used during the course of the study to assess alcohol use and alcohol craving. Safety will be assessed, including monitoring the severity, causality and frequency of all adverse events, vital signs, and physical and neurological examination.

A Study of the Effect of a Nurse Navigator Program on High Risk Patients

The purpose of this study is to examine if educational intervention in high risk patients can lead to decreased hospital readmissions when compared to patients who are not in the intervention program. Additionally, to determine patient satisfaction with the educational program.

Behavioral and Functional Task Development, Implementation, and Testing

Background: \- Scientists know that alcohol use disorders affect brain structure. They want to know more about the effects of alcohol use disorders on a person s behavior. They want to develop tasks that can be done inside a scanner that can help them better understand these effects in later studies. Objective: \- To develop tasks that investigate a person s behavior that can be used in later studies. Eligibility: * Inpatient participants of another study. They must be physically healthy right-handed adults 18-60 years old. * Healthy right-handed volunteers 18-65 years old. Design: * Participants will be screened with medical history and physical exam. They will have an EKG to record heart activity. They will give blood and urine samples and have a psychiatric interview. * Participants will have between one and three visits. * Participants will be asked about their alcohol drinking to see if they have an alcohol use disorder. * Participants will complete one of three simple computerized tasks either inside the magnetic resonance imagining (MRI) scanner or outside of it. * The MRI scanner takes pictures of the brain. The scanner is a metal cylinder. Participants lie on a table that can slide in and out of the cylinder. They will be in the scanner for about 60 minutes. They may have to lie still for up to 20 minutes. The scanner makes loud knocking noises, but they will get earplugs.

Stand Down-Think Before You Drink: An RCT of a Mobile App for Hazardous Drinking With Peer Phone Support

Hazardous drinking is common among Veteran primary care patients and increases risk for more costly and complex medical problems over the long-term. Yet, the vast majority of these Veterans go untreated. By providing an option for care that is easily accessible, private, and self-directed, mobile applications (apps) circumvent many barriers to alcohol use treatment. However, poor patient engagement remains the Achilles' heel of these apps. Through supportive accountability, Peer Specialists can maximize the reach and engagement of these apps with patients and improve drinking outcomes. The goal of this project is to evaluate whether an app for alcohol use self-management ("Stand Down") reduces drinking among Veteran primary care patients who engage in hazardous drinking, and for whom Peer-Supported-Stand Down is more effective than the app alone. If successful, the proposed research has the potential to transform care and increase access to alcohol-related services for Veterans who engage in hazardous drinking but rarely seek treatment, and, in turn, mitigate the adverse health outcomes that stem from untreated hazardous drinking.

Telehealth Treatment for Alcohol Use Disorder

Participants with alcohol use disorder will be randomly assigned to either the Ria Treatment Platform or a waitlist control. The Ria Treatment Platform is a telehealth approach that incorporates medical assessment, medications for alcohol use disorder, individual and group coaching, educational video modules, and a Bluetooth-enabled breathalyzer. Patients are followed for three months during which data are collected, including measures of alcohol consumption and its consequences.

Effects of Tirzepatide on Alcohol Intake in Patients Diagnosed With Schizophrenia and Alcohol Use Disorder

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for the treatment of type 2 diabetes and obesity, have shown promise as a novel treatment for alcohol use disorder (AUD). This study aims to investigate whether the Glucose-dependent Insulinotropic Polypeptide/GLP-1RA tirzepatide will reduce alcohol consumption in patients with a dual diagnosis of AUD and schizophrenia, a population in dire need of improved treatment options. To further investigate the neurobiological underpinnings of a potential dampening effect on alcohol consumption, functional magnetic resonance imaging (fMRI) brain scans will be applied. The key anticipated outcomes include: * decreased alcohol consumption and * reduced alcohol cue-induced brain activity in the GIP/GLP-1-treated patient group compared with the placebo group. To the best of the investigators knowledge, this has never been examined before.

A Trial to Investigate the Effects of Cannabidiol Plus Naltrexone on Alcohol Craving in Patients With Alcohol Dependence

Alcohol addiction (AD) is a chronic relapsing disorder with currently limited pharmacological treatment options. Alcohol craving, a hallmark symptom of AD that drives relapse in patients, is only insufficiently treated by existing medication. One promising new compound for the treatment of alcohol craving in AD is Cannabidiol (CBD), which showed beneficial effects on alcohol craving in preliminary clinical studies. Additionally, CBD seems to be a particularly promising candidate for enhancing the effects of established medication, specifically Naltrexone (NTX), an opioid-antagonist, which is approved for AD treatment, due to the synergistic effects of the combination of Cannabidiol plus Naltrexone on alcohol consumption that were shown by preclinical studies. The proposed three-armed, 1:1:1 randomized, double-blind, placebo-controlled parallel group, multicentric phase II trial seeks to test the putative synergistic effects of combined CBD (800mg) + oral NTX (50mg) against CBD (1200mg) + oral NTX (50mg) against Placebo + oral NTX (50mg) on alcohol craving (primary outcome) in male and female patients with AD that suffer from high alcohol craving. The trial seeks to test the effects of the innovative combination of CBD plus NTX against Placebo plus NTX on alcohol craving over a 14-day treatment period, which is embedded in a standardized addiction treatment program according to current treatment guidelines, in order to estimate the added value of treatment with CBD on alcohol craving. Quality of life and neurobiological and biochemical markers for craving will serve as secondary outcomes, because they show strong associations to treatment outcome and relapse risk. Collection and analysis of follow-up data (28 days, 42 days, 105 days, 196 days) will be performed to determine whether treatment effects relate to patient outcome.

Naltrexone in AUD Reward Drinkers

This study is a phase IV, two-arm, randomized, double-blind, placebo-controlled study to assess whether individuals identified as primarily reward drinkers are significantly more likely to reduce heavy drinking if they receive XR-NTX than a matching placebo injection. Study subjects will receive monthly injections of long-acting injectable naltrexone 380 mg (4 mL) or matching placebo. All subjects will also receive 4 sessions of Medical Management (MM). Post-treatment follow-up visits will be conducted at 4 weeks after the scheduled completion of treatment.

Suicidal Behavior in Patients Diagnosed With Bipolar Disorder

The purpose of this study is to learn the environmental and psychological factors that impact suicidality in patients diagnosed with Bipolar Disorder. Additionally, the study aims to identify treatments to reduce the suicidal behavior and improve quality of life through a 6-week group-based intervention program.

Cohort Study on Medical Students' Mental Health

The main objective of this study is to identify risk factors for depression among medical students by comparing them to students who completed their first year but did not enter the medical program (students not accepted into the second year of medical school). Major Depressive Disorder (MDD) will be assessed using a validated tool: the Composite International Diagnostic Interview Short-Form (CIDI-SF). This a prospective, longitudinal, cohort study. The plan is to inform each new cohort of students at the Orléans University Hospital medical school for 10 years. It is estimated that 5,000 to 10,000 students will be able to participate in the study. A link to access the study questionnaire will be sent to students by email via the registrar's office, with one email per week for four weeks. The email will contain a link to a web page where the questionnaire can be completed. The questionnaire will be available online on computers or smartphones for six weeks: from mid-October to the end of November. The questionnaire will be completed each year for the duration of the study or until the student completes their studies. Duration of the inclusion period: 10 years Duration of participation for each participant: maximum 12 years Total duration of the study: 22 years As the cohort progresses, longitudinal analyses may be conducted to study the evolution of various disorders over time, adjusting for known confounding factors. Following the initial analyses of this study, a new interventional study will be set up to identify students at risk and offer them appropriate care.

Ketamine and Neurofeedback as Combined Therapeutic Interventions to Target Glutamatergic Neurotransmission in Alcohol Use Disorder

The goal of this clinical trial is to learn about the effects of the combination of ketamine and realtime functional magnetic resonance imaging (fMRI) neurofeedback training on the treatment of individuals with alcohol use disorder (AUD). The main questions the investigators aim to answer are: * Can the investigators observe a positive, significant therapeutic effect by comparing changes in alcohol use via i) mean alcohol use per day, ii) heavy drinking days one month after the last treatment intervention? * Are changes in glutamatergic neurotransmission in the nucleus accumbens related to cue-induced cravings in individuals with AUD? * Is there a significant, ketamine-dependent change in glutamate levels in the nucleus accumbens? Participants will be given ketamine or placebo and real-time fMRI neurofeedback (rt-fMRI NFT) or sham rt-fMRI NFT. The investigators will compare three intervention groups to investigate the effects of the stand-alone effects as well as potential synergies between the combination of pharmacological and non-pharmacological intervention.

Alcohol Misuse Treatment to Patients Newly Diagnosed With Alcohol-related Liver Disease: a Randomized Controlled Trial

To evaluate the efficacy of systematically offering newly diagnosed ALD patients to AUD treatment, in the hepatology clinic, on alcohol abstinence after 6 months. The investigators will conduct a randomized controlled superiority trial with parallel group design, hypothesis blinding and blinded outcome assessment comparing A) a offer to specialized AUD treatment (intervention) and B) standard care (control). Existing observational cohort ALD members will contribute to the control group in addition to the randomized controls. The primary outcome is abstinence throughout the last 30 days assessed 6 months after randomization.

Alcohol and the Social Brain: An Alcohol-Administration Hyperscanning Study Employing a Within-Subject Design

The study investigates the effects of alcohol consumption on social and individual behaviors using a within-subject design. Participants, aged 21-30, will attend two laboratory sessions approximately one week apart, participating as part of a dyad (pair). During one session, they will consume an alcoholic beverage, while in the other, they will receive a control beverage, with the order of conditions randomized. This design facilitates direct within-participant comparisons of behaviors and neural activity in intoxicated versus sober states. To achieve these aims, the study employs EEG technology to explore intra-brain and inter-brain dynamics during social interactions. Additionally, validated self-report questionnaires will capture data on mood, social bonding, and other psychological variables. The findings are expected to enhance understanding of alcohol's role in social reward processes and contribute to developing evidence-based prevention and intervention strategies for alcohol use disorder.

Developing Functional Connectivity-Guided TMS for Alcohol Use Disorder

Alcohol Use Disorders are currently positioned as the third leading cause of preventable death in the United States, constituting a humanitarian crisis with substantial financial burden on society and medical facilities. While several pharmacological interventions exist, 60% of individuals who seek these treatments relapse to alcohol within 6 months. These high relapse rates are due in part to elevated brain response to alcohol cues in the environment. This study seeks to evaluate the efficacy of one session of functional Magnetic Resonance Imaging (fMRI) guided transcranial magnetic stimulation (TMS) as a strategy to reduce brain reactivity to alcohol cues.

CRP and S&A for Inpatient Veterans

The purpose of this study is to evaluate how well three types of treatments work to improve the outcomes for people with substance use problems. Veterans admitted to the Charleston VA Psychiatric inpatient unit may be invited to participate. The three types of treatments that will be evaluated are: 1. Combined Recovery Program (CRP), a six-session treatment group delivered on the inpatient unit. 2. A Home Telehealth program, called Stable and Able (S\&A), provided just prior to discharge and provides additional support for up to 3 months 3. Treatment-as-usual (TAU), which is the treatment currently provided on the unit, consisting of various mental health topics and sessions designed to help with recovery. Participation begins on the inpatient unit, beginning with CRP and/or TAU, and may continue with S\&A post discharge. Participants will be followed up at 1 and 3- months post treatment.

Ibudilast for Treating Alcohol Use Disorder

This is a research study involving 6 weeks of study medication, Ibudilast or a placebo (an inactive substance) and medical management counseling to reduce or stop drinking. Ibudilast is not approved by the U.S. FDA for clinical use in the United States, but it is has been used for many years in Japan for its anti-inflammatory effects. Its use in the treatment of alcohol dependence is experimental. By reducing inflammation, Ibudilast may help some people reduce or stop drinking. We have obtained an Investigational New Drug Application (IND) approval for this study from the FDA. Ibudilast has been used clinically for 20 years in Asia for treating bronchial asthma and, more recently, for post-stroke dizziness and ocular allergies and has been shown to be safe and well tolerated.

Effectiveness of High-frequency rTMS in Reducing Alcohol Consumption in Non-abstinent Patients With an Alcohol Use Disorder

The fight against alcoholism is a public health priority. Around 15 million Europeans and 10 million North Americans are alcohol dependent. Worldwide, 1 death out of 25 is thought to be attributed to alcohol. In France, the latest published data on alcohol-related mortality indicates that there were 49,000 alcohol-related deaths in 2009. Alcohol is thought to be the leading cause of hospitalisation for French people, and its social cost is estimated at 37.4 billion euros. However, few patients with an alcohol use disorder are treated: less than 8% in Europe and less than 10.5% in the USA receive appropriate treatment for their alcohol problem. This low rate of treatment is mainly due to the fact that these patients are not ready to stop drinking. They are therefore not attracted by the goal of abstinence that is required by most current therapies and drug treatments. The arrival of new treatments aimed at reducing consumption (rather than abstinence) should make treatment more attractive. To date, nalmefen is the only treatment marketed for this indication. Baclofen should be marketed in 2020, but with restrictive prescription criteria. In this new strategy to reduce consumption, brain stimulation could play a predominant role as an alternative or complementary therapy. Indeed, functional brain imaging techniques have made it possible to visualise the cortical regions involved in craving, in particular the dorsolateral prefrontal cortex (DLPFC). Craving, i.e. the irrepressible desire to consume, is often at the origin of consumption and relapse. Stimulation of the dorsolateral prefrontal cortex with non-invasive cerebral stimulation techniques, such as repeated transcranial magnetic stimulation (rTMS), has provided encouraging results for the reduction of cravings in all addictive behaviours (alcohol, tobacco, cocaine, food). Furthermore, stimulation of the DLPFC seems to modulate decision-making processes: it may thus reduce impulsivity and strengthen inhibitory control, leading to a reduction in substance use. The hypothesis to be tested is that repeated transcranial magnetic stimulation allows a reduction in alcohol consumption in patients with an alcohol use disorder.

Comparing Combined Behavioral Intervention and Ericksonian Hypnotherapy for Alcohol Addiction

This clinical study is being conducted to compare the effectiveness of two psychological treatments for alcohol addiction: Combined Behavioral Intervention (CBI) and Ericksonian Hypnotherapy (EH). The purpose of the study is to determine whether Ericksonian Hypnotherapy, a more personalized and indirect therapeutic method, is equal to or more effective than the gold-standard approach, Combined Behavioral Intervention, in helping individuals reduce their alcohol consumption and improve psychological well-being. Alcohol addiction is a serious condition that affects mental, emotional, and physical health. Many treatment options exist, but not all individuals respond in the same way. This study aims to evaluate two different types of therapy in a structured way, to better understand which works best, for whom, and under what circumstances. The study will include 90 adult participants diagnosed with Alcohol Use Disorder (AUD). Participants will be randomly assigned to one of three groups: (1) a group receiving weekly sessions of Combined Behavioral Intervention, (2) a group receiving weekly sessions of Ericksonian Hypnotherapy, or (3) a control group receiving general educational materials about alcohol addiction. Treatment will last for 12 weeks, and all participants will be followed up three months after the last session to assess long-term effects. Throughout the study, researchers will measure changes in alcohol consumption, alcohol craving, mental health symptoms (such as depression and anxiety), quality of life, and motivation to change. The findings of this study may help improve the way alcohol addiction is treated by offering evidence on alternative approaches such as hypnotherapy.

Ketamine Alcohol (in Treatment-Resistant Depression)

A single subanesthetic dose infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and robust antidepressant effects in patients with treatment-refractory major depressive disorder (TRD). A family history of an alcohol use disorder (Family History Positive, FHP) is one of the strongest identified predictors of an improved antidepressant response to ketamine. Like ketamine, alcohol is a functional NMDA receptor antagonist. FHP is associated with differential response to ketamine, e.g. blunted psychotomimetic side effects. One of the primary mechanistic hypotheses for ketamine's antidepressant action is the acute intrasynaptic release of glutamate from major output neurons, e.g. cortical pyramidal cells. Preliminary clinical studies have demonstrated this acute glutamate "surge" in response to subanesthetic dose ketamine. Based on these findings, the investigators hypothesize that ketamine's enhanced antidepressant efficacy in FHP TRD subjects is, at least in part, attributable to increased glutamate release relative to TRD subjects without a family history of alcohol use disorder (Family History Negative, FHN). To test this hypothesis, the investigators have designed a now two-site, open-label study of 18-55-year-old medically and neurologically healthy, currently moderately-to-severely depressed TRD patients. In total, the investigators plan to recruit 25 FHP and 25 FHN TRD subjects. All subjects must not have a current substance use disorder (except nicotine or caffeine). The experimental portion consists of two phases. The preliminary first phase is a medication taper (if needed) and psychotropic medication-free period. The experimental second phase comprises one subanesthetic dose (0.5mg/kg x 40 minute) ketamine infusion. The ketamine infusion will occur during 7T-magnetic resonance imaging (MRI), both resting-state functional MRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) to detect glutamate in the ventromedial prefrontal cortex/ventral anterior cingulate cortex (vmPFC/vACC). The primary outcome measure is group mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-ketamine infusion (baseline) to one-week post-infusion, where the investigators observed ketamine's greatest antidepressant effect in FHP TRD. Additional outcome measures are vmPFC/vACC glutamate change in response to ketamine based on family history status. In summary, this study will provide key mechanistic information on ketamine's improved antidepressant efficacy in a biologically-enriched subgroup. This will contribute to the systematic development of more efficacious, personalized treatments for major depression in an effort to reduce its enormous public health burden.

Behavioral Alcohol Responses (BAR) Study

This study aims to identify risk factors that prospectively predict alcohol problems in young adults.

Assessing Habitual, Goal-Directed, and Pavlovian Influences in Alcohol Use Disorder

The first aim of this study is to establish the role of maladaptive reliance on habits for impaired control in addiction, employing a novel task - the Action-Sequence-Task (AST), which assesses interference between habitual and goal-directed control. The AST, along with the developed computational model, will be employed to test whether participants with Alcohol Use Disorder (AUD) and control participants differ with respect to task performance and estimated model parameters. The investigators hypothesize stronger habitual behavior (increased habitual tendency) and an increased susceptibility to conflict between habitual and goal-directed control, measured as increased interference, are associated with AUD. The second aim of the study is to understand whether Pavlovian-to-Instrumental Transfer (PIT) reflects more of a controlled, goal-directed process, or a more automatic, habitual process. The investigators will use the single-lever PIT task as it is an efficient tool for testing the interaction between Pavlovian cues and instrumental behavior, especially when they are in conflict. In these trials, top-down control must be allocated to successfully overcome the conflict, which may share some common underlying mechanisms with the arbitration between goal-directed and habitual behavior during conflict, as assessed by the novel AST. The third aim of the study is to investigate whether severely dependent AUD patients would show a stronger PIT effect compared to a control group, consistent with the investigators' previous findings.