Tagged Clinical Trials

Experimental Stem Cell Treatment Leaves 3 Women Blind

An experimental treatment — which blinded three women after stem cells from abdominal fat were injected into their eyes — was advertised on a government-run clinical trial website but lacked proper safeguards, researchers reported Wednesday.

The report in the New England Journal of Medicine notes that the procedures were part of a national rise in the number of clinics harnessing stem cells from fat to treat a variety of diseases — even though many have not been proven to work. Two of the women thought they were getting treatment as part of a clinical trial because they learned about the procedure on clinicaltrials.gov, a database run by the National Library of Medicine that features thousands of studies, many of which are sanctioned by research organizations and have regulatory oversight.

Jeffrey Goldberg, professor and chairman of ophthalmology at the Byers Eye Institute at Stanford University and co-author of the study, said the report aims to highlight the ethical implications of how clinical research is defined for the public and the dangers of poorly regulated trials.

“I would emphasize it’s a challenge and we can’t expect patients to fully vet these options,” he said. “And that’s where the ethics of the doctors and oversight of regulatory agencies need to play a role in the public health of our community.”

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The women featured in the report sought treatment in 2015 for age-related macular degeneration, a common, progressive eye condition characterized by blurriness in the center field of vision. Their ages ranged from 72 to 88, the report said, and they paid $5,000 for the procedure. Each had both eyes treated at the same time, a protocol that is “both atypical and unsafe,” according to the researchers.

The report did not name the clinics involved in the study or its sponsor. Researchers said in a press release accompanying the study that the clinic is no longer performing the procedures but is still treating patients.

Clinicaltrials.gov shows the trial referenced in the article was sponsored by a stem cell company based in Sunrise, Fla., called Bioheart Inc., now known as U.S. Stem Cell. Dr. Shareen Greenbaum served as the trial’s principal investigator, according to the company’s press release. She is an ophthalmologist working at the Hollywood Eye Institute in Cooper City, Fla.

According to the journal report, clinicians used cells extracted from fat, and treated them with enzymes to obtain the stem cells. Blood was also drawn from the patient and then platelet-dense plasma was extracted. The cells were then mixed with plasma and injected into both eyes.

Within days, the three patients sought medical care for complications related to the procedure. Two patients suffered bleeding and each had retina detachments. The researchers said they are not expected to regain their sight.

The analysis said that the consent forms signed by the women did not mention a clinical trial. It also noted that the patients paid for the procedure and both eyes were treated at the same time, a protocol that is “both atypical and unsafe.” The patients paid for procedures “that had never been studied in a clinical trial, lacked sufficient safety data and was performed in both eyes on the same day,” the researchers wrote.

State insurance records show insurers for Greenbaum, U.S. Stem Cell and a registered nurse paid out more than $3 million in 2016 to patients harmed by stem cell procedures, although it is not clear if those patients are the same ones detailed in the study. U.S. Stem Cell said in a statement Wednesday that it could not comment on these cases but it is committed to “research and development of effective cell technologies.” The statement noted that the company has “successfully conducted more than 7,000 stem cell procedures with less than 0.01% adverse reactions” since 2001. Greenbaum did not return calls for comment.

Stem cells have unique properties that researchers believe may hold promise for new treatments for a host of diseases such as diabetes and arthritis. These cells have the ability to change into different types of specialized cells and act as a repair system for tissues throughout the body.

Hundreds of stem cell clinics have sprung up across the nation offering therapies. But many of these medical interventions have not been vetted through federal protocols for safety and effectiveness. Because stem cells are harvested from the patient who will receive the treatment, many of these clinicians say they do not need the Food and Drug Administration’s approval, said Karen Maschke, a research scholar at the Hastings Center, a bioethics research institute.

In the journal report, the authors hypothesize the adverse effects of the treatment were caused by stem cells transforming into myofibroblasts, or cells that can lead to scarring. Enzymes used to extract the stem cells could have also contaminated the solution.

But the report said even if the treatment had caused no adverse effects, there’s little evidence showing that it would have worked.

Formal clinical trials have several safeguards to protect participants against adverse effects, said Maschke. Biomedical trials are overseen by an institutional review board that is responsible for reviewing the study’s research protocol to ensure participants are being protected. Patients are also required to sign consent forms that outline the risks associated with the experiment.

For large clinical trials, a separate oversight group called a data safety monitoring board conducts reviews throughout the trial to assess the risks and benefits of the experiment, Maschke said. Smaller and less dangerous trials rely on the research team and chief investigators to notify the IRB of any safety issues. Participants can also report their concerns to the Office for Human Research Protections within the Department of Health and Human Services.

Dr. Thomas Albini, one of the co-authors and an associate professor of clinical ophthalmology at the University of Miami, warned consumers that clinical trials with a fee should be carefully reviewed. “I’m not aware of any legitimate research, at least in ophthalmology, that is patient funded,” he said in the press release accompanying the study.

The government website recently expanded its requirements for clinical trials wishing to register on the site. However, Maschke said she isn’t sure whether the new rules will lead to a more rigorous vetting process for prospective listings.

“It’s unclear whether or not anyone is enforcing required postings and what’s supposed to be in them,” she said.

Categories: Cost and Quality, Public Health, Syndicate

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Pursuing the Dream of Healthy Aging

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Credit Paul Rogers

Given their druthers, most people would opt for a long and healthy life. Few relish the idea of spending years, even decades, incapacitated by illness, dependent on caregivers and unable to enjoy the people, places and activities that make life worth living.

In 1980, Dr. James F. Fries, a Stanford University physician who studied chronic disease and aging, proposed that a “compression of morbidity” would enable most people to remain healthy until a certain age, perhaps 85, then die naturally or after only a brief illness.

Now, a prescient group of experts on aging envisions a route to realizing Dr. Fries’s proposal: one or more drugs that can slow the rate of aging and the development of the costly, debilitating chronic ailments that typically accompany it. If successful, not only would their approach make healthy longevity a reality for many more people, but it could also save money. They say that even a 20 percent cut in how fast people age could save more than $7 trillion over the next half-century in the United States alone.

“Aging is by far the best predictor of whether people will develop a chronic disease like atherosclerotic heart disease, stroke, cancer, dementia or osteoarthritis,” Dr. James L. Kirkland, director of the Kogod Center on Aging at the Mayo Clinic, said in an interview. “Aging way outstrips all other risk factors.”

He and fellow researchers, who call themselves “geroscientists,” are hardly hucksters hawking magic elixirs to extend life. Rather, they are university scientists joined together by the American Federation for Aging Research to promote a new approach to healthier aging, which may — or may not — be accompanied by a longer life. They plan to test one or more substances that have already been studied in animals, and which show initial promise in people, in hopes of finding one that will keep more of us healthier longer.

As Dr. Kirkland wrote in a new book, “Aging: The Longevity Dividend”: “By targeting fundamental aging processes, it may be possible to delay, prevent, alleviate or treat the major age-related chronic disorders as a group instead of one at a time.”

His colleague S. Jay Olshansky, a gerontology specialist in the School of Public Health at the University of Illinois in Chicago, said it is often counterproductive to treat one disease at a time. Preventing cardiac death, for example, can leave a person vulnerable to cancer or dementia, he explained.

A better approach, Dr. Kirkland said, would be to target the processes fundamental to aging that underlie all age-related chronic diseases: chronic low-grade inflammation unrelated to infection; cellular degradation; damage to major molecules like DNA, proteins and sugars; and failure of stem cells and other progenitor cells to function properly.

The team, which includes Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in The Bronx, and Steven N. Austad, who heads the biology department at the University of Alabama at Birmingham, plans to study one promising compound, a generic drug called metformin already widely used in people with Type 2 diabetes. They will test the drug in a placebo-controlled trial involving 3,000 elderly people to see if it will delay the development or progression of a variety of age-related ailments, including heart disease, cancer and dementia. Their job now is to raise the $50 million or so needed to conduct the study for the five years they expect it will take to determine whether the concept has merit.

The project represents a radical departure from ordinary drug studies that test treatments for single diseases. However, the group, spearheaded by Dr. Barzilai, said the Food and Drug Administration has endorsed their idea to test a single substance for effectiveness against a range of ailments.

“If metformin turns out not to work, there are several other substances in the pipeline that could be tried,” Dr. Barzilai said. “Under the auspices of the National Institute on Aging, three research centers have tested 16 substances in different animal models and got incredible results with four of them.”

Green tea, one of those tested, bestowed no health or life span benefits, despite its popularity. But the drug rapamycin, an immune modulator used following organ transplants, was most effective among those tested, Dr. Barzilai said.

The team is starting with metformin because it is a cheap oral drug — costing about two cents a pill — with six decades of safe use in people throughout the world. Among those with Type 2 diabetes who have taken it for years, there is evidence suggesting that, in addition to diabetes, it protects against cardiovascular disease, cancer and possibly cognitive impairment, Dr. Kirkland said, adding that “it targets the fundamental processes of aging, which tend to be linked.”

Dr. Barzilai said, “Our goal is to establish the principle of using a drug, or two in combination, to extend health span. The best we can expect from metformin is two or three additional years of healthy aging. But the next generation of drugs will be much more potent.”

Dr. Barzilai is already conducting a complementary study of centenarians, the results of which could identify more drugs to delay age-related diseases. He and colleagues are isolating genes that appear to keep these long-lived men and women healthy for 20 to 30 years longer than other people and shorten the length of illness at life’s end. Several studies have already found that individuals with exceptional longevity experience a compression of morbidity and spend a smaller percentage of their life being ill, Dr. Barzilai and his colleague Dr. Sofiya Milman wrote in the “Aging” book.

By analyzing the action of genes that extend health span, “it should be possible to devise drugs that mimic the genes’ effects,” he said. Two such gene-based drugs that show early promise against age-related diseases are already being tested.

But until definitive studies are completed and substances are shown to be safe as well as effective in prolonging health, Dr. Olshansky cautioned against dosing oneself prematurely with widely touted substances like resveratrol, the antioxidant found in red grapes and wine, or growth hormone.

Consumers must exercise caution, he warned, because “there’s an entire industry out there trying to market the products we’re testing before they are adequately evaluated.”

He also emphasized that taking a drug found to ward off age-related ills is not a license to abandon a healthy lifestyle. Doing so “could completely negate the benefit of a compound that slows aging,” he said.

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