NCT05997212

Effect of Repetitive TMS on Executive Function in Alcohol Use Disorder

Effect of Repetitive Transcranial Magnetic Stimulation on the Executive Function in Alcohol Use Disorder

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sponsor: Universidad Nacional Autonoma de Mexico · Academic / Other
• Sex: All
• Age: 25 Years – 59 Years
• Healthy volunteers: Not accepted

Summary

Alcohol Use Disorder (AUD) is a major public health problem that affects the physical, social, family, and mental integrity of the sufferer. Behavioral self-regulation is compromised in AUD, and a benefit has been reported with the application of repetitive transcranial magnetic stimulation and emotional self-regulation. The aim of this study is to investigate the efficacy of high-frequency rTMS to improve executive functions in patients in abstinence from AUD.

Detailed description

It is proposed that individuals predisposed to developing alcohol use disorder (AUD) exhibit alterations in executive functions, resulting from maladaptive cellular homeostatic processes and neuronal circuits activated by substance use. These alterations persist even after substance withdrawal (Nestler \& Aghajanian, 1997). As a multifactorial disorder, AUD has been linked to family history of alcohol use (Khemiri et al., 2020; Peterson et al., 1990; Tarter et al., 1989) and individual traits such as poor cognitive test performance relative to controls (Shnitko et al., 2018; Goudriaan et al., 2011), which may predict heavy alcohol consumption or AUD development. These executive dysfunctions manifest as persistent negative behaviors that impede adaptive learning and reduced activation of the executive control network, both of which correlate with AUD severity (Mayhugh et al., 2014). Cognitive flexibility, a key executive function, enables adaptive adjustment of thoughts and behaviors in response to environmental demands (Uddin, 2021). Impaired cognitive flexibility is associated with AUD persistence and severity (Stalnaker et al., 2008), though recovery is observed after prolonged abstinence (Rourke \& Grant, 1999). Thus, cognitive flexibility may serve as a promising treatment biomarker. McLellan et al. (2000) report that 40-60% of AUD patients relapse within the first year post-treatment, while at least 60% relapse within six months (Durazzo \& Meyerhoff, 2017; Kirshenbaum et al., 2009; Maisto et al., 2006a; Meyerhoff \& Durazzo, 2010). Given these challenges, non-invasive neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) have emerged as adjunct therapies to standard treatments (Diana et al., 2017). For example, Addolorato et al. (2017) applied high-frequency (10 Hz) rTMS to the dorsolateral prefrontal cortex (DLPFC) in AUD patients and observed reduced alcohol consumption and increased abstinent days. Similarly, Del Felice et al. (2016) found that left DLPFC stimulation enhanced inhibitory control, selective attention, and mood in active alcohol users. Stimulating the DLPFC, a hub of the executive control network, may enhance its functional connectivity and improve cognitive flexibility in AUD patients. These effects align with findings that rTMS bolsters inhibitory control and attention (Del Felice et al., 2016; Diana et al., 2017). To explore this further, we propose a longitudinal study assessing cognitive/behavioral traits in AUD patients that may contribute to disorder development. We will also evaluate rTMS effects using neuropsychological tools and MRI to measure structural/functional brain changes. This study aims to investigate the short- and long-term clinical and cognitive effects of 10 Hz rTMS applied to the left DLPFC in abstinent AUD patients, alongside associated neurostructural and functional connectivity changes. Abstinent AUD patients will receive daily rTMS for four weeks. Clinical outcomes will be tracked for six months, with cognitive, structural, and functional connectivity measurements taken at baseline, post-intervention (4 weeks), and follow-up (6 months).

Conditions

• Alcohol Use Disorder

Interventions

Type	Name	Description
DEVICE	Repetitive Transcranial Magnetic Stimulation	The investigators will use a Magstim Rapid 2 stimulator, Airfilled coil (AFC), 8 shape (magnetic field of 0.8 Teslas, 3Kg, pulse 0.5 ms) Each patient will receive high frequency 10 Hz stimulation at 100% of motor threshold over the dorsolateral prefrontal cortex (DLPFC) at 1500 pulses per session with 30 trains of 5 seconds and 0.5 ms stimuli and an inter-train distance of 15 seconds. In 2 daily sessions 4 days a week for 4 weeks.
DEVICE	Repetitive Transcranial Magnetic Stimulation (Sham)	The investigators will use a Magstim Rapid 2 stimulator, Airfilled coil (AFC), 8 shape (magnetic field of 0.8 Teslas, 3Kg, pulse 0.5 ms) Each patient will receive consistent treatment in 2 sessions a day for 20 consecutive business days for 4 weeks. The coil will be placed on the vertex target location.

Timeline

• Start date: 2024-03-16
• Primary completion: 2025-07-01
• Completion: 2026-11-01
• First posted: 2023-08-18
• Last updated: 2025-02-10

Locations

1 site across 1 country: Mexico