OSU-CHS researcher studying if weight loss drugs could be used to treat alcohol use disorder
Thursday, November 9, 2023
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Semaglutide, the medication in the popular diabetes and weight loss drugs Ozempic and Wegovy, continues making headlines. What if it could also help curb substance use disorder or addiction?
Dr. Kyle Simmons, Professor of Pharmacology and Physiology at Oklahoma State University Center for Health Sciences, is leading the Semaglutide Therapy for Alcohol Reduction (STAR) study in Tulsa. Below, he answers questions about semaglutide, his study and how people can participate.
Q: What is the STAR study?
A: STAR, officially known as the Semaglutide Therapy for Alcohol Reduction study, is a double-blind study that aims to investigate whether the medication semaglutide, also known by trade names Ozempic or Wegovy, can be used to treat alcohol use disorder. It explores the potential for semaglutide, originally developed for diabetes and obesity treatment, to have broader applications.
Q: What's a double-blind study, and why is it important?
A: The study follows a gold-standard research design, which involves double-blind, placebo-controlled clinical trials. This means that neither the participants nor the researchers interacting with them know whether the participant is receiving the actual medication — semaglutide — or a placebo, a substance with no active effects. This design helps ensure the results are not influenced by biases and that any observed effects are genuinely linked to the medication.
Q: How does semaglutide work in the body?
A: Semaglutide is a molecule that mimics a natural hormone called glucagon-like peptide 1 (GLP-1) produced by the intestine after eating. GLP-1 signals the brain to reduce the desire for food, essentially making us feel less hungry. Semaglutide is administered as a once-weekly subcutaneous injection and it stays in the body for about a week. It may potentially decrease the desire for rewarding substances, such as alcohol.
Q: Can you explain how semaglutide affects the brain's reward system?
A: Semaglutide binds to receptors in the brain involved in dopamine signaling, particularly in areas like the ventral striatum, which includes the nucleus accumbens. These brain regions play a significant role in making us want and enjoy things that make us feel good. They are critical for motivating us to seek out and enjoy rewarding experiences.
Q: How long does the STAR study last, and who else is involved?
A: The STAR study in Tulsa lasts for 12 weeks. The study involves thorough screening, baseline measurements and neuroimaging. Participants receive the medication or a placebo for 12 weeks, and then the changes in their behavior, brain activity and biomarkers are examined at the end of those 12 weeks.
Q: Can you elaborate on what participants can expect?
A: Participants go through a rigorous screening process, including health and medical assessments, to ensure their safety. Once enrolled in the study, they have a baseline visit, which involves various evaluations. These evaluations include measuring behaviors like drinking, smoking, and eating habits, as well as assessing their mood and overall life circumstances. Additionally, the study collects data on circulating proteins, often referred to as biomarkers, using blood and saliva samples. Participants also undergo neuroimaging and they’re even exposed to a virtual reality environment. This process is repeated after 12 weeks, during which participants receive either the medication or a placebo. The focus is not only on changes in their drinking behavior but also on how their brain activity and various bodily systems, such as endocrine, metabolic, and immune pathways, may be linked to these changes.
Q: You mentioned neuroimaging. What does it examine or show you?
A: Neuroimaging involves looking at the structure and function of the brain. Functional Magnetic Resonance Imaging (fMRI) is used to see how the brain responds to certain tasks. The structural and functional images are overlaid on each other, helping researchers map how brain function relates to brain structure.
Q: Are there concerns that semaglutide could affect other rewarding behaviors?
A: Yes, there's a concern that semaglutide might not only reduce the desire for harmful substances like alcohol but also affect other rewarding behaviors, potentially leading to anhedonia, a loss of interest in pleasure. It's extremely important that we figure that out because that helps us to understand who this medication would be safe for and who it wouldn't. This is an important aspect to study, especially in people with a history of conditions like major depressive disorder. We're also being very careful to measure changes in mood and anxiety.
Q: What is the significance of the sister study happening at the National Institute of Drug Abuse (NIDA) and how did it come about?
A: Dr. Lorenzo Leggio is an investigator at NIDA intramural research program. While NIDA typically funds research at universities across the country, they also have an in-house research program. Dr. Leggio, who is a principal investigator at NIDA and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), also serves as the clinical director. He has decades of experience in conducting research in this field.
Interestingly, this collaboration began almost two years ago when a colleague played matchmaker and introduced us to work on a review paper for a special issue of a journal. Before this, we were aware of each other's research but had never met. During our initial Zoom call, we started discussing our respective studies and found that our labs had independently designed nearly identical studies. We shared the same interest in investigating the GLP-1 mechanism's potential for treating alcohol use disorder, selected similar dosages, and even planned to use the same measures.
This realization led to a unique moment where we had to decide whether to compete or collaborate. Both Lorenzo and I have a natural inclination toward collaboration, so we decided to work together. We now have two separate studies that are closely harmonized. While his study takes place independently at NIDA in Baltimore, we've gone to great lengths to align our studies in terms of the measures used.
Q: What's the significance of multiple research teams working on this simultaneously?
A: This collaboration will provide a robust replication of the findings, which is vital in today's scientific landscape. Replicating results in different populations and research teams enhances the credibility of our findings. This is particularly significant because if semaglutide proves to be effective in treating alcohol use disorder, it will expedite its clinical implementation. We're still in the process of finding out whether it's effective or not, but replication is a key step in making any breakthrough accessible to patients. It's exciting that different research teams are studying the same medication because they can pool their findings to get a more comprehensive understanding of its effects. This collaborative approach helps determine who the medication is safe and effective for.
Q: Can people still join the study, and if so, how do they begin the screening process?
A: We are actively enrolling for the study. We have an online screener that collects the necessary information to determine if they might be a suitable candidate for the study. Once we have the initial screening information, we reach out to the interested individuals to start the screening process. Currently, we are about 20 percent of the way through the study, and our goal is to add about one person per week to the study. It's a complex process, but we have an excellent research team and colleagues, making recruitment relatively smooth. For those who believe they might be candidates and are experiencing a relatively high level of weekly alcohol consumption, I encourage them to reach out and complete the online screener to see if they qualify for the study. The entire study is expected to last approximately two years, with about another year and a half or year and three-quarters to go. After the study's completion, we will analyze the data and publish the results. We are also closely collaborating with our colleagues at NIDA in Baltimore to understand the similarities and differences in our findings.
Q: How was the STAR study funded?
A: The Hardesty Family Foundation made a generous donation to create the Hardesty Center for Clinical Research in Neuroscience at OSU. They also funded the STAR study to investigate the potential use of semaglutide for alcohol use disorder. The foundation's support has been instrumental in making the study possible and has contributed to putting OSU-CHS on the national and international stage. The study's funding and support have been crucial in moving the research forward. I'm incredibly grateful to my colleagues here at OSU-CHS, to the team that we have here, to our administration that has been very supportive of this, and again, particularly to the Hardesty Family Foundation for their support. This wouldn't happen without them.
Q: How did you first become interested in research specifically centered on substance use disorder?
A: My grandfather had a lifelong battle with what we now call alcohol use disorder. He eventually achieved a measure of sobriety and started a business in the 1950s and 1960s that produced items like sobriety chips and coins for organizations like AA. I got involved in this family business from a young age, helping with orders, stocking shelves, and even attending conventions where we supplied materials to groups around the country. And it was a great experience. I mean, it gave me a real-world, very personal connection to this group of people who are struggling with this disease. At a young age, I saw that recovery is possible. Today, it definitely motivates me.
Q: As you conduct this study, what do you want people facing alcohol use disorder to remember?
A: This is a clinical trial to discover initial evidence of whether semaglutide is safe and effective in humans for alcohol use disorder treatment. We don't know if it is. If patients are struggling with alcohol use disorder and they want treatment for it, there are good treatments, and they can reach out to their care provider to access those treatments, and they really should be accessing those FDA-approved treatments. There are already gold-standard double-blind placebo-controlled RCT trials that show their efficacy. I really want people to do that rather than just trying to go out and get semaglutide for alcohol use disorder.