On Monday, the National Institutes of Health (NIH) announced that it opened phase II clinical trials on four potential treatments for long COVID spanning drugs, medical devices, biologics, and other therapies. The trials are a part of the NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative, a $1.5 billion research program launched in 2021 to identify how people recover from COVID-19 as well as those people who are at risk of developing post-acute sequelae of SARS-CoV-2 (PASC). The initiative also works with patients and clinicians across the country to find ways to both prevent and treat the long-term effects of COVID.
“We know that when patients are suffering, we can never move fast enough,” said acting NIH director Lawrence A. Tabak, DDS, PhD in a press release. “NIH is committed to a highly coordinated and scientifically rigorous approach to find treatments that will provide relief for the millions of people living with long COVID.”
The trials, which are informed by findings from RECOVER will focus on several of the symptoms patients with long COVID have described as most burdensome and have the potential to provide long COVID patients with relief sooner than an individual study. The initial stages of the two-year-old effort saw NIH launch broad observational, multi-site studies to examine and follow people over time to track their symptoms of COVID and attempt to find reasons why some people develop long-terms symptoms from COVID, while others recover completely. To date, RECOVER has recruited more than 24,000 participants, which researching analyzing more than 60 million electronic health records and running more than 40 pathology studies on the effects of COVID on different organs. These data were the foundation of the development of the phase II trials.
“Hundreds of RECOVER investigators and research participants are working hard to uncover the biologic causes of long COVID. The condition affects nearly all body systems and presents with more than 200 symptoms,” said Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, and co-leader of the RECOVER Initiative. “Recognizing that more than one solution is likely needed, we’ve taken the lessons learned from RECOVER participants to design rigorous clinical trial platforms that will identify treatments for persons with different symptom clusters to improve their function and well-being.”
The adaptive trials launched yesterday will focus on viral persistence and cognitive dysfunction and are dubbed RECOVER-Vital and RECOVER-Neuro.
RECOVER-Vital has an initial focus on a treatment targeting SARS-CoV-2 persistence. This portion of the trial will test a longer dose regimen of the FDA-approved antiviral Paxlovid (nirmatrelvir and ritonavir) to see if it improves long COVID symptoms. Persistence of the virus has the potential to effect proper immune system function as well as organ damage. Trials sites are already enrolling patients in this portion of the trial.
RECOVER-Neuro will seek to discover clinical interventions for cognitive dysfunction often associated with long COVID, including brain fog, memory problems, difficulty with attention, thinking clearly, and problem solving. This trial will test three different interventions:
- BrainHQ, developed by Posit Science Corporation in San Francisco, that has been used to improve cognitive function;
- PASC-Cognitive Recovery, a web-based goal management training program that has been used for improving executive function, developed by Mount Sinai Health System;
- A home-based transcranial direct current stimulation device developed by Soterix Medical, Woodbridge, NJ.
Other trials that are planned, but not yet launched as their protocols are still under review include:
- RECOVER-Sleep will conduct a placebo-controlled trial for hypersomnia, or excessive daytime sleepiness, testing two wakefulness-promoting drugs, and a second trial for sleep disturbances, such as problems falling or staying asleep, testing other interventions designed to improve sleep quality to learn if these interventions may help regulate sleep patterns in adults with long COVID.
- RECOVER-Autonomic will comprise two arms to examine interventions to help treat symptoms associated with problems in the autonomic nervous system, which controls a range of bodily functions including heart rate, breathing and digestive system activity. The initial trial will focus on postural orthostatic tachycardia syndrome (POTS), a disorder with symptoms that include i irregular heartbeat, dizziness and fatigue. The first arm will evaluate a treatment used for immune diseases versus placebo. The second arm will evaluate a drug currently used to treat chronic heart failure in people with an elevated heart rate versus placebo. Participants within each arm will then be randomized to receive either more intensive coordinated care that does not involve additional medication, or usual care.
A fifth adaptive trial on exercise intolerance and fatigue is also under development.
The trials will continue to launch and enroll participants on a rolling basis at sites across the U.S. Selected sites will demonstrate a verified history of enrolling diverse patient populations, which was a vital criterion for site selection.
