How one study is being conducted soley on-line

E-mail follow-ups being used

The St. Louis-based genomic medicine development company GenoMed is taking a novel approach to testing its hypothesis that inflammation-reducing heart medications can be effective in treating severe complications of influenza. A notice on the company web site invites people to consider participating in a clinical trial to determine whether taking angiotensin-I converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs) will help prevent or reduce the severity of symptoms of influenza.

Study participants are recruited solely via the web site — an on-line informed consent form is available — and potential participants are instructed to print out the form and take it to their personal physician, who will prescribe an appropriate dose of one of the medications. Subjects will also only be followed via periodic e-mail questionnaires — no face-to-face visits involved.

"We’ll be following up with participants every few weeks to see how they are doing," says GenoMed’s president, CEO and chief medical officer David W. Moskowitz, MD, MA, FACP. "We’ve found that people don’t always answer their e-mail, and to expect about a 10%-20% yield. Still, that’s not bad for a free study."

The theory 

A nephrologist by training, Moskowitz believes that a mutation associated with the angiotensin-I converting enzyme gene causes an overexpression of this enzyme, which leads to an overactive inflammatory immune response. It is this response that Moskowitz contends plays a leading role in the development of a number of common adult diseases, and that ACE inhibitors can actually be used to treat a number of different illnesses.

Among patients prescribed ACE inhibitors and ARBs for diabetic nephropathy and other complications, he has observed that many experienced an improvement in the incidence of inflammatory diseases.

Thus, Moskowitz speculates that use of these medications could reduce the severe, debilitating response that many people experience after exposure to influenza, West Nile virus (WNV), and the SARS-related coronavirus.

To find an answer, Moskowitz last summer designed a similar clinical trial to test whether ACE inhibitors and ARBs were effective treatments for West Nile virus.

The study only had 14 participants, but 11 of those participants did not experience severe complications due to WNV. Of the three treatment failures, two patients were in a coma state when treatment was initiated, and the third was already immunocompromised when the study began. The data were useful in determining that the treatment would not work in patients whose illness had already progressed to coma and in patients who are immunosuppressed.

So in the current trial, only healthy, immunocompetent subjects will be included.

The subjects themselves will decide whether to: a) begin taking the drug immediately in hopes of preventing the development of flu at all; and b) whether to take an ACE inhibitor or ARB.

"If enough people hear about the study, they will fill out both limbs [ensuring enough data to have statistically significant results]," Moskowitz says. "This is very much a study concept based on the concept of If you make it available, they will come.’"

For comparison, the researchers will use the seasonal influenza morbidity and attack rate data collected by the CDC to determine whether their subjects did better than the population as a whole.

In follow-up e-mails to subjects, Moskowitz intends to ask about any adverse reactions or side effects, although the risk for this is small, he says. The drugs have been on the market for decades and have been demonstrated to be very safe.

An IRB is not monitoring the clinical trial because, Moskowitz says, there is no one IRB with jurisdiction, and the trial is not supported by any entity that would require IRB supervision.

"We receive no money from any agency that requires the use of an IRB, nor are we performing the research for the benefit of any agency, such as the FDA, which requires an IRB," he points out. "The essence of the Nuremberg laws about medical research in 1946 was informed consent. IRBs were added only in the 1950s. In fact, each person’s physician will be functioning in the capacity of an IRB, as a learned, objective, dispassionate observer with their patients’ best interests at heart. In this capacity, a physician will be even more stringent than a remote, IRB-for-hire. "

At some point, the company hopes to be able to afford to hire an IRB to monitor future studies, but in the meantime, Moskowitz says he believes it is important for this type of low-risk, potentially high-benefit study to proceed.

The difficulty in conducting randomized, controlled trials for every medication or planned treatment is that each trial costs an exorbitant amount of money, he explains.

"In the very old days, pre-1960s, the NIH would pay for many of these kinds of trials; then the drug companies picked up most of the tab," Moskowitz continues. "With the tremendous consolidation of the research pharmaceutical industry beginning 10-15 years ago, much clinical research has gone unfunded."

Investigators must try to do the best they can with the limited amount of funding available, he says. It is important for researchers examining potential new uses for existing drugs to operate with more flexibility.

"I think we’re back to the early days of medicine in the 19th and early 20th centuries, when individual physicians would collect consecutive case series and report about them," he adds. "The randomized, controlled trial is a luxury that we simply cannot afford. As we discover more disease-causing genes, society needs to get used to the idea that research techniques will regress in sophistication for the next few decades — the alternative is no to harvest the riches before us, which any clinician will tell you is morally and professionally unacceptable."

For more information about the GenoMed studies, visit the company’s web site at www.genomed.com.