SC Connecticut News

Health limitations, distance, work schedules, family obligations, and financial constraints are all barriers that prevent patients from participating in clinical trials. For those living with Long COVID, debilitating symptoms can make traveling to a study site impossible.

Harlan Krumholz, MD, Harold H. Hines Jr. Professor of Medicine (Cardiology), is pioneering a new approach that makes participation in clinical research accessible for those whose lives have been upended by the post-acute infection syndrome. At Yale School of Medicine, working closely with Sterling Professor Akiko Iwasaki, PhD, he is the principal investigator of the Yale Paxlovid for Long COVID (PAX LC) Trial. This phase 2 investigational new drug clinical trial evaluates the use of the antiviral for people with Long COVID using a decentralized nationwide design that brings the research into participants’ homes. Operating throughout the contiguous United States, it is the first fully decentralized phase 2 trial with this complexity and scale.

Krumholz believes that this trial demonstrates that a future of clinical research allowing patients to participate at their convenience is not only possible but more efficient and cost-effective than standard clinical trials.

For example, April 9 marked Cindy’s* fourth anniversary of living with Long COVID. It started with severe fatigue followed by shortness of breath and gastrointestinal issues after she was infected with COVID-19 in 2020. Her symptoms never went away. A single mom in Texas with a 6-year-old son, she says the disease forced her to get creative: She made up a game where he rolled a ball around her while she lay still on their trampoline.

Over the years, her symptoms have ebbed and flowed. She suffered a sharp decline in January 2022 — during the Omicron wave — when she was hit with her second acute COVID infection. This triggered a slow decline affecting her cognitive abilities and eventually forcing her to take a leave of absence from her job as an aerospace engineer in fall 2023. She began experiencing another common Long COVID symptom known as post-exertional malaise (PEM), which significantly worsened after physical or mental activity.

“I was known for thinking outside of the box,” she says. “Suddenly, everything seemed so complicated... I was just trying to survive day-by-day.”

Desperate for answers, Cindy stayed on top of ongoing clinical trials but faced challenges due to accessibility issues until she came across the PAX LC Trial. Typically participating in a Connecticut-based university trial would have been impossible for her; however, YSM's team brought the study to patients no matter where they lived in the U.S., sending drugs or placebos via mail and collecting samples at home or nearby labs.

“The Pax LC trial is a historic contribution to the evolution of a new way of doing trials,” Krumholz says.

Researchers currently have several hypotheses for Long COVID's underlying causes including persistent virus remnants and autoimmune dysfunction among others. The Pax LC Trial tests one such hypothesis: persistent virus remnants.

Cindy initiated prescreening by filling out surveys about pre-existing conditions and syncing medical records through an app on her phone before moving forward months later by giving blood samples locally and adjusting medications accordingly once enrolled receiving either Paxlovid or placebo via mail while tracking symptoms electronically daily along providing periodic blood/saliva samples some collected at home others nearby labs making life easier according Cindy who appreciated having technicians visit home minimizing disruption overall process despite concierge-like service being less expensive compared traditional methods according Krumholz benefiting both patients researchers alike reforming structure hindering innovation ensuring better retention diversity participants contributing scientific progress faster cheaper effectively accommodating constraints creating sense community through virtual town halls engaging participants keeping them informed encouraging involvement without obligation necessary fostering willingness join future endeavors further revolutionizing field ultimately enabling quicker solutions broader applications beyond just addressing long covid challenges extending potential benefits various populations inspiring adoption participant-centric formats across board demonstrating feasibility efficacy decentralized approaches promising brighter future medicine