The National Institutes of Health (NIH) is set to initiate a series of clinical trials aiming to investigate potential treatments for long-term symptoms experienced after COVID-19 infection. These symptoms include sleep disturbances, exercise intolerance, and post-exertional malaise (PEM), which refers to the worsening of symptoms following physical or mental exertion.

Part of the NIH's Researching COVID to Enhance Recovery (RECOVER) Initiative, these mid-stage trials will join six other ongoing studies that focus on viral persistence, neurological symptoms, and autonomic nervous system dysfunction. They aim to enroll around 1,660 individuals across 50 study sites in the United States, with the objective of finding effective treatments for the most common and burdensome symptoms reported by those suffering from long COVID.

Walter J. Koroshetz, M.D., the director of NIH's National Institute of Neurological Disorders and Stroke and co-lead of the RECOVER Initiative, expressed the importance of alleviating these disruptive and devastating symptoms. He highlighted the challenges faced by individuals who struggle with disrupted sleep, exercise intolerance, and feeling sick after once simple tasks. Koroshetz emphasized the need for answers to help those with long COVID regain their sense of well-being.

The upcoming RECOVER-SLEEP clinical trials will explore the effectiveness of two drugs, modafinil and solriamfetol, which are approved by the Food and Drug Administration for the treatment of hypersomnia, a condition characterized by excessive daytime sleepiness. These medications have not been extensively studied in people with long COVID. Participants will be randomly assigned to receive either the active study drug or a placebo control for a period of eight to ten weeks, depending on the assigned drug.

Another trial under the RECOVER-SLEEP initiative will focus on testing potential treatments for complex sleep disturbances associated with long COVID. This includes the use of melatonin, an over-the-counter supplement commonly utilized for sleep disorders, and light therapy, which helps individuals reset their sleep cycles. Participants will be randomly assigned to receive either melatonin or a placebo control, as well as high-intensity or low-intensity light therapy, throughout the course of eight weeks.

The RECOVER-ENERGIZE clinical trials will be launched to examine a program called personalized cardiopulmonary rehabilitation. This program combines exercise training, strength and flexibility training, education, and social support to help individuals with exercise intolerance, shortness of breath, and fatigue during physical activity post-COVID-19 infection. Participants will undergo randomized assignment to either receive personalized cardiopulmonary rehabilitation or basic exercise education for a three-month period.

Additionally, the RECOVER-ENERGIZE trials will test a program known as structured pacing, designed to help participants manage and minimize symptoms of post-exertional malaise developed after COVID-19 infection. This program focuses on regulating and pacing daily activities without involving exercise training or physical movement to prevent exacerbating symptoms. Participants will be randomly assigned to receive either structured pacing with a trained coach or basic post-exertional malaise education for three months.

All four trials have been designed with extensive input from the community and patient representatives, with a particular focus on patient safety concerns. Lucinda Bateman, M.D., an expert in post-exertional malaise and founder of the Bateman Horne Center, expressed the importance of testing the effectiveness of structured pacing and educating patients on activity management.

Diversity and inclusivity in trial participants are considered high priorities for the RECOVER Initiative. Study sites are chosen based on geographic location, their connections to communities, and their successful recruitment of diverse research participants. The initiative aims to create one of the largest and most diverse groups of long COVID study participants globally.

With the launch of these four studies, the NIH's RECOVER Initiative now conducts 13 treatments across eight clinical trials, continuing to enroll participants. Those interested in learning more about the trials can visit trials.recovercovid.org.

The NIH's Researching COVID to Enhance Recovery (RECOVER) Initiative, together with its partner organizations and patient representatives, is dedicated to understanding, diagnosing, and treating long COVID. As part of the broader government-wide effort to address long COVID, these clinical trials contribute to the advancement of prevention, diagnosis, treatment, and provision of services for individuals experiencing long-term COVID-19 effects.

The NIH, as the nation's leading medical research agency, aims to investigate the causes, treatments, and cures for both common and rare diseases. Through its extensive programs and research efforts, the NIH is committed to turning discovery into health and improving the lives of individuals affected by long COVID.

For more information about the NIH and its programs, visit www.nih.gov.