How Alzheimer’s Clinical Trials Have Become COVID-19 Victims

GAP President, John Dwyer, and GAP-Net site Great Lakes Clinical Trial spoke on the hit Alzheimer’s clinical trials have taken since COVID-19, and the losses that will come of it.

After a frustrating 2019, Alzheimer’s researchers had reason to look forward to 2020 as a year of promise. Then the pandemic struck.

“Last year, seven [Alzheimer’s clinical] trials were stopped. The portfolio was more than halved,” said John R. Dwyer, Jr., president of the Global Alzheimer’s Platform (GAP) foundation, a network for clinical trials in North America.

Clinical trials with human participants are needed to test the safety and effectiveness of any new Alzheimer’s drugs or treatments to prevent, slow or cure the disease.

Alzheimer’s studies take a long time to conclude. There hasn’t been a successful treatment approved since 2003,” Dwyer said.

Setting Back Alzheimer’s Research

Private clinical trial sites have been particularly hard hit because of COVID-19 restrictions. “If sites fail, that loss of research capacity could set back Alzheimer’s research for years,” Dwyer noted.

The disruption in clinical trials might have an irreversible effect on the health and wellbeing of Alzheimer’s patients and their caregivers.

Before the pandemic, Alzheimer’s researchers were hopeful that 2020 could have been a breakthrough year for the nearly 6 million Americans living with the disease and for their caregivers. The National Institutes of Health was set to allocate $2.8 billion for dementia research, a nearly threefold increase over 2016.

But the disruption in clinical trials might have an irreversible effect on the health and wellbeing of Alzheimer’s patients and their caregivers, said Steve Satek, president of Great Lakes Clinical Trials in Chicago.

“The greatest hope for treating this disease lies in clinical trials. That is where the most cutting-edge, innovative medicines can be found,” he noted. “A person who is experiencing gradual memory loss cannot put that decline on hold while we wait to start up or reactivate trials. Their disease moves on.”

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As of the beginning of April, only 12% of research centers were enrolling in any clinical trials, according to reports to GAP. Some said they could be closing their doors in the next few months; more than half said they may need to lay off staff.

Workarounds to Keep Alzheimer’s Clinical Trials Going

In some cases, Alzheimer’s researchers have been devising alternatives to lower the number of required visits vulnerable older participants must make to health care facilities for the trials. Home visits and telemedicine are taking up some of the slack. But these workarounds add another degree of difficulty to an already complex process, according to Dwyer.

Observational studies, which don’t involve the introduction of an actual drug or treatment, are not considered essential to participants’ health. So, they “have pretty much shut down,” according to Dr. Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute (ATRI) at the University of Southern California.

But interventional or therapeutic trials where participants receive some type of treatment are more likely to be considered essential. That has allowed some of them to continue, albeit with difficulties. But “at many sites, we have had to put a hiatus in place. It’s very disruptive,” said Aisen.

These tests are rigorous, Aisen noted, adding that “when you already have a study underway, it’s critical to try to maintain it, to try to keep the dosing on schedule” at home or in a setting that does not put participants at risk.

A Major Clinical Trial Pushed Back

One major Alzheimer’s study ATRI is participating in is known as the AHEAD 3-45. It’s a global multicenter clinical trial aimed at preventing memory loss due to Alzheimer’s disease. This study was poised to launch in May but had to be pushed back until at least mid-July.

“For a number of reasons, participation in AHEAD 3-45 cannot be done at home. The screening process requires in-person cognitive and clinical assessment, as well as MRI and PET brain imaging,” said Aisen. “In addition, the study medication is administered intravenously.”

Despite the delays, many Alzheimer’s clinical trial participants remain committed. “We’re confident we are going to be able to complete studies,” said Aisen. “There will be delays, it will require adjustments, but we will complete and evaluate therapies.”

However, Li-Huei Tsai, director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, is much less confident that her institute will be able to complete trials to test non-invasive brain simulation.

“We will still have useful data, but there may be limits on some outcome measures compared to what we would have had without the pandemic.”

“We had tested animals with light and sound, and this reduced Alzheimer’s pathology and improved cognitive function,” according to Tsai. Based on that research, “we designed a study to have human subjects receive light and sound one hour a day for a year.”

‘Completely Disrupted’

A device consisting of a 2’x2? panel designed to produce the gamma frequency light and a speaker producing the gamma frequency sound was installed in each participant’s home. One group had been receiving treatment and the second group got a placebo. Caregivers were instructed how to monitor the treatment.

Although use of the device has not been much affected by the pandemic, “our ability to bring subjects back for evaluation is completely disrupted,” said Tsai. “I don’t see any time soon that we will be able to evaluate them.”

The pandemic is requiring Tsai and her team to make changes to a painstakingly designed protocol, setting research back by at least six months.

“We will still have useful data, but there may be limits on some outcome measures compared to what we would have had without the pandemic,” Tsai said.

Many participants had agreed to sign on to the trial with the understanding that even if they were initially given the placebo they’d later be switched to the actual treatment. With that possibility indefinitely on hold, Tsai said, “I feel bad.”

She’s also concerned about the ability to expand the light/sound study and to begin other trials.

The Pandemic’s Biggest Impact on Alzheimer’s Research

Satek sees the inability to screen new patients for trials as “probably the biggest impact” of the pandemic for Alzheimer’s research.

That’s because it takes years of working within a community to convince people to participate in clinical trials.

Said Satek: “Normally we bring in ten to fifteen people a week for free memory tests. That doesn’t mean they will join a trial, but a lot do” once they’re educated about how trials work. Now, few people are coming in for free tests.

And although Great Lake Clinical Trials has remained open during the coronavirus outbreak, the nearby hospital that provides MRI and PET scans closed its imaging center for weeks, along with other services, to prevent the spread of COVID-19.

As a result, some people temporarily couldn’t get the brain scans they needed to enter the program and the clinic had to postpone follow-up scans for trial participants who’d already enrolled.

Challenges for Doing the Tests at Home

Since most Alzheimer’s medications under study haven’t been approved for prescription by the Food and Drug Administration, having patients take the medicine at home and report the results makes the assessment more challenging, Satek said.

“We still need to assess the patient’s safety via physical exam, ECG and  lab tests and perform standardized cognitive and quality of life assessments. This could possibly be done in the home setting as long as it is approved by our ethics board and study sponsor. But it would require assembling a traveling research team,” he added.

And entering homes opens the door to questions about COVID-19 safety for the patients as well as the researchers.

For people visiting his clinic, Satek said, numerous steps have been taken to protect against the coronavirus.

Patients are reminded to stay home if they show any COVID-19 symptoms. And for social distancing, “we don’t have two people coming to the waiting area at the same time,” said Satek.

Also, interviews with new patients and memory assessments have been moved from small rooms to larger conference rooms and offices.

How to Attract New Clinical Trial Participants

In an effort to keep the pipeline of new trial participants from drying up, Satek has been conducting Zoom meetings and virtual memory assessments.

“It’s going pretty well. We ask them: ‘Do you want to be called when things open again?’ We keep them on the list,” Satek noted.

In the past, he often spoke to groups in person about the importance of volunteering for clinical trials. Those talks have moved online, too.

“It takes years to build up a presence in the community. We’re doing our best to keep the momentum going. We’re focused on trying to keep the information river flowing,” said Satek.

Still, Dwyer worries about the pipeline of participants drying up. “Healthy folks are needed, sick people are needed,” he said.

He encourages people concerned about getting Alzheimer’s to enter clinical trials. “You’re going to get the best neurological workups. A complete review of your cognitive situation. Even if you don’t go into a study, you get information,” Dwyer said.

These days, he’s especially concerned that small, family-owned private clinics won’t survive the current economic crisis.

More than half of Alzheimer’s studies are done in what Dwyer calls this “capillary system.” Getting financial relief to them “is more of a challenge. There’s not a natural mechanism to get them help,” Dwyer noted.

If these small clinics don’t get some type of small-business relief from the government, Dwyer said, their capacity will be reduced 20% to 30%.

“That means that one full Alzheimer’s trial will not get done. We lose one more big shot on goal,” said Dwyer.

Originally posted by Next Avenue on July 9, 2020.

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