Effectiveness of Non-invasive Neuromodulation in Patients With Long-COVID
NCT Number: NCT06456502
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Long-COVID|Post-acute COVID-19 Syndrome
Interventions: DEVICE: Non-invasive neuromodulation|OTHER: Placebo
Sponsor: Universidad Rey Juan Carlos
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 44
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-06
Completion Date: 2026-06-30
Locations: Rey Juan Carlos University, Alcorcón, Madrid, 28922, Spain

Summary:
Sleep quality and duration are critical to cognitive, emotional and physical well-being, and poor sleep quality has been associated with an increased risk of cognitive, psychological and cardiometabolic disorders. Several important physiological activities occur during sleep including a reduction in heart rate and blood pressure. In addition, sleep exerts important modulatory effects on hormone release. Previous studies have shown that lack of sleep can generate exaggerated cortisol responses or psychological and physiological stressors. Cortisol has widespread effects throughout the body and brain, affecting mood, arousal, energy, metabolic processes, and immune and inflammatory system functioning. Therefore, disruptions in cortisol secretion during the night can influence a wide variety of processes in our body that may contribute to the perception of poorer sleep quality. In addition, the salivary enzyme α-amylase is considered a biomarker of cognitive, psychosocial, emotional or physical stress. It is important to note that the autonomic nervous system (ANS) regulates several physiological processes, including heart rate, blood pressure, respiration, and digestion. The ANS consists primarily of the sympathetic system and the parasympathetic system. Increased parasympathetic activity is considered to promote health, whereas a dominant or overactive sympathetic branch is considered to be detrimental to health.

A recent study found that both sleep quality and quantity of sleep were associated with resting ANS functioning. They found that poorer sleep quality was associated with greater sympathetic dominance. Research on the sympathetic and parasympathetic branches of the ANS has shown that autonomic imbalances are precursors to disease formation and other health-related risks. Coronavirus disease 2019 (COVID-19), has in many cases involved the presence of long-lasting symptoms several weeks or months after surviving acute infection with the virus, leading to a new disease called long COVID-19 or post-COVID-19 syndrome (PCS). A recent study showed that sleep quality influences the relationship between symptoms associated with sensitization and mood disorders with health-related quality of life in people suffering from long COVID.

Non-invasive neuromodulation directed to ANS may be an option to treat the sleep disorders observed in patients with long COVID.

OBJETIVES:

Therefore, the primary objective of this study is to evaluate the efficacy of a treatment protocol on the ANS by means of non-invasive neuromodulation in aspects related to sleep in long COVID patients compared to placebo. As secondary objectives, we propose to evaluate the efficacy of a treatment protocol on the ANS by non-invasive neuromodulation in aspects related to ANS functioning, psychological variables, fatigue, pain perception and quality of life in patients with long COVID.

Primary Outcome Measures: Sleep quality, The aspects of sleep to be assessed by means of the Pittsburgh sleep quality index (PSQI) scale and the sleep diary to be completed each morning and handed in on the last day of treatment., Baseline, at the of 15th session, at 6 month an at one year
Secondary Outcome Measures: Heart variability, Through the We Cardio device, which provides variables such as resting heart rate (HRV) and the root mean square difference of successive interval between two successive R-waves (RMSSD), which reflects beat-to-beat variation in heart rate and is the main time-domain measure used to estimate vagal (parasympathetic) changes reflected in HRV., Baseline and at 8 weeks|Cortisol and alpha amylase levels, Cortisol and alpha amylase levels will be assessed with salivary tests that will be analyzed using a Soma cube reader device., Baseline and at 8 weeks|Psychological variables, Depression and anxiety will be evaluated by means of the hospital anxiety and depression scale (HADS) validated in spanish and with a high level of reliability and sensitivity for these variables, Baseline, at 8 weeks, at 6 month an at one year|The quality of life, This variable will be evaluated by means of the EuroQol 5D (EQ-5D). It is a standardized instrument developed to describe and assess health-related quality of life (HRQoL), Baseline, at 8 weeks, at 6 month an at one year|Disability, The impact of the disease on patients will be assessed using the severe acute respiratory syndrome (SARS) functional impairment checklist (FIC), which is a questionnaire that assesses physical and psychological symptoms, as well as disability-related domains. The FIC has been shown to be valid, to show good reliability and to exhibit good psychometric properties for use as a tool to assess physical symptoms and disability-related domains in patients with SARS and patients with persistent COVID., Baseline, at 8 weeks, at 6 month an at one year|Pain intensity, Pain will be assessed by means of a numeric pain rating scale (NPRS), which allows measuring the intensity of pain described by the patient with maximum reproducibility between observers., Baseline, at 8 weeks, at 6 month an at one year