The first two of the long-awaited long COVID clinical trials from the RECOVER initiative are underway, the NIH said.
RECOVER-NEURO, which will study interventions for long COVID cognitive dysfunction, and RECOVER-VITAL, a study targeting viral persistence, are opening enrollment, said Acting NIH Director Lawrence Tabak, DDS, PhD, in a press briefing today.
Two other trials, RECOVER-SLEEP and RECOVER-AUTONOMIC, will launch soon.
“The trials can test multiple treatments simultaneously and be quickly adapted to evaluate new therapies,” Tabak said. “They are designed not only to stand on their own, but also to inform one another. While each trial focuses on certain symptom clusters, they also collect data about the impact of the intervention on a broad range of symptoms.”
The trials follow a platform protocol, allowing multiple targeted therapies to be tested in the same study.
RECOVER-NEURO, for example, will test a web-based training program called BrainHQ, a goal-management training program known as PASC-Cognitive Recovery, and transcranial direct current stimulation. RECOVER-VITAL will focus initially on treating SARS-CoV-2 persistence; its first intervention will test a long regimen — up to 25 days — of the antiviral nirmatrelvir/ritonavir (Paxlovid). (Nirmatrelvir/ritonavir also is being studied in a Yale University long COVID study; a previous study of the antiviral at Stanford University was stopped early.)
RECOVER-SLEEP will test interventions for changes in sleep patterns or ability to sleep after having COVID-19, including melatonin and sleep coaching. RECOVER-AUTONOMIC will focus first on postural orthostatic tachycardia syndrome (POTS), and will test multiple drugs in several arms.
The biologic underpinnings of long COVID are still not understood, observed Walter Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke. “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,” he said.
Each RECOVER study will be a phase II trial and can adjust rapidly as needed. “The goal of these trials is to evaluate safety and efficacy of interventions,” said Kanecia Zimmerman, MD, PhD, MPH, principal investigator of the RECOVER Clinical Trials Data Coordinating Center at the Duke Clinical Research Institute in Durham, North Carolina.
“This is a step in the right direction,” noted Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University in St. Louis, and chief of research at the VA St. Louis Health Care System, who has conducted large observational studies of long COVID.
“We have been waiting for this for 3 years, so it is good to see this effort finally launched,” Al-Aly told MedPage Today. “I think there needs to be a greater sense of urgency around long COVID. Millions of patients are suffering en masse, and we need to meet the challenge of the moment with greater urgency and resolve.”
But this effort might not be comprehensive enough, Al-Aly added. “The scope seems to not take into account a lot of the hypotheses about the underlying mechanisms of long COVID,” he said. “There is nothing in there about microclots, microbiome, and other potential mechanisms.”
Overall, more than 200 symptoms are associated with long COVID. Earlier this year, researchers identified 12 key symptoms associated with long COVID and provided a framework to define it.
Also today, HHS announced it is forming the Office of Long COVID Research and Practice, which will be under the leadership of Assistant Secretary for Health, Admiral Rachel Levine, MD. The new office will coordinate efforts of 14 federal departments that work on long COVID, with a goal of improving quality of life and reducing disparities for people with long COVID symptoms.
“Last year, President Biden called on HHS to coordinate the response to long COVID,” HHS Secretary Xavier Becerra said in a statement. “The official establishment of the Long COVID Coordinating office and the launch of the RECOVER clinical trials solidifies this issue as an ongoing priority.”
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