Subjects wanted: Cooley Dickinson launches clinical trials

By LISA LINSLEY Bulletin Contributing Writer

Published on February 05, 2010

You may have received one of the neon-yellow fliers in the mail: "Are you or someone you know ...75 years of age or older and not taking a Vitamin D supplement? ..."

If you read it closely instead of tossing it out, you would have learned that the flier, sent by Jennifer Higgins at Cooley Dickinson Hospital in Northampton, is recruiting candidates for a study to determine whether or not taking the vitamin affects cognitive performance, that is, the way a person processes information or applies knowledge.

It's the first of several clinical trial studies planned at Cooley Dickinson in a collaborative venture the hospital has forged with Massachusetts General Hospital in Boston, according to Higgins, coordinator of the local program.

The study, a Phase IV trial that has low risk to participants, aims to gauge the effects of Vitamin D. "There is a large body of scientific literature supporting a relationship between Vitamin D levels and neurological function," said Higgins. Yet, she says, as far as she can tell, the Cooley Dickinson study is the first to administer Vitamin D in an attempt to influence cognitive performance.

Conducted by Dr. David Alpern of Northampton, the research will involve 50 people 75 years and older who will be randomly assigned to take either a Vitamin D supplement or a placebo over a three- to six-month period.

Before and after taking the Vitamin D supplements participants will take written tests to determine how they are processing information. Currently 45 patients are being prescreened, says Higgins.

Selling the program

Higgins, a graduate of the Ph.D. program in gerontology at the University of Massachusetts, was hired in April to head the clinical trials program at Cooley Dickinson. She says a study focused on heart failure will be next, followed by studies of various cancers. Funded by the National Cancer Institute, these will focus on breast, colon, rectal, bladder and blood cancers, she says, and will test the effects of medications and various combinations of medications. The tests are still awaiting approval by the International Review Board of the National Research Center in Boulder, Colo., she says, and will be available later in the month.

To explain the hospital's new program, and to recruit participants, Higgins has been using the mail, distributing fliers and holding public forums, like one at the Amherst Senior Center at the Bangs Community Center in Amherst last month.

Through a PowerPoint presentation and question-and-answer session Higgins explained that clinical trial research, which tests new drugs, surgeries or devices, must follow safety and ethics rules set out by the International Review Board and the Belmont Report, which was issued by the United States Department of Health and Human Services following a string of unethical research experiments.

In addition to obtaining informed consent from the participants before a study begins, researchers must follow guidelines for protecting the participants' physical and emotional well-being and communicating diagnoses, results and effects of the tests, she said. Higgins noted that a clinical trial would be discontinued if it was found to be causing ill effects in subjects. In addition, participants are allowed to leave a study at any time, she said.

Clinical trials can be both public and privately funded, Higgins told the group. In its association with Mass General, Cooley Dickinson is receiving money through the National Cancer Institute, specifically the Cancer and Leukemia Group B (CALGB).

Levels of risk

The Cooley Dickinson trials are categorized as Phase III or Phase IV studies in a five-tier system that reflects the degree of invasiveness and risk, said Higgins. Phase 0 is a study in which the tiniest trace of a substance first being used in humans is introduced to the body. It is not a treatment; instead it tests how the body processes a drug and whether it produces the same results in humans as in preclinical studies, she said. This phase usually includes only 10 to 15 participants.

Phase I is technically the first step in testing a new treatment in humans, said Higgins. "These studies usually include only a limited number of patients who would not be helped by other known treatments," she said. They are designed for people who are at the end stages of their lives, according to Higgins. A medication to treat HIV or terminal cancer would fall into the Phase I category.

Phase II studies focus on the effects of treatments that have already passed Phase I safety testing. They are performed on larger groups of up to 300 participants and examine, for instance, whether a new treatment shrinks a tumor or improves blood test results. Phase II testing will not be offered at Cooley Dickinson, said Higgins. It is more likely to be done at teaching hospitals, like Mass General.

A Phase III trial may include hundreds of people across the country and looks at treatment as it progresses. Studies would only move into Phase III after treatment shows promise in Phases I and II, Higgins said. "Phase IV is the next growing body of clinical trials," she said. "Phase IV is referred to as post-market studies, at the behest of sponsors. They are generally longer term and very low risk to participants." Phase IV studies include medications or treatments that have already been approved for use. The Vitamin D study would fall into the category of a Phase IV study because Vitamin D supplements are already on the market and used for other purposes, Higgins said.

A Phase IV trial also involves testing another function of a product or medication, such as the link between Vitamin D and cognition.

Benefits anticipated

While the hospital and society at large can benefit from trials such as those conducted at Cooley Dickinson, Higgins stressed in her talk that there are benefits for participants as well.

Patients, she pointed out, will have access to treatments and medications that would not be available elsewhere, and, they receive this treatment at no cost. In addition, some of the studies offer stipends to subjects to reimburse them for their time, transportation expenses or inconvenience. However, Higgins has found that many patients find promising medication or treatment a more motivating factor than payment. "Others may want to give back to their family, or science, mankind. For instance, if a disease is common in their family, they may want to participate in research for that disease," Higgins said.

Some members of the Amherst audience expressed concern about receiving a placebo rather than the actual medication. "For me it's difficult," said Richard Koffler, 74. "If you have a need to know or if you are a person who likes to be in control, knowing whether you are getting a placebo would be important to me."

Cooley Dickinson Hospital, Higgins said, intends to expand its clinical trials program over time, offering the community increased access to cutting-edge medications and treatments.

"Prior to Cooley Dickinson offering these trials, they were only offered in metropolitan areas," she said. "We want to make them locally available for those who have limiting factors such as difficulty accessing transportation."

The heart failure trials up next, which will be conducted by Dr. James Kirchhoffer of Northampton Cardiology Associates and Cooley Dickinson Hospital, will test a new defibrillator, an external device to treat heart attacks, said Higgins. Kirchhoffer is seeking 10 participants who have had recent heart attacks and who are at least 18 years old.

According to the National Cancer Institute, an estimated 70 percent of patients express willingness to participate in clinical trials, and 98 percent of trial participants report feeling satisfied with their participation.

"The community benefit of the trials," says Higgins, "is that it enables the extension of education and treatment and prevention into the community."

In the case of the Vitamin D study, she said, "We anticipate these findings will be most dramatically evident in the over-75-year age group. As the population of older adults continues to rise, any intervention which can stave off cognitive decline would be quite beneficial to our society."

For more information about the clinical trials at Cooley Dickinson, contact Jennifer Higgins at 582-4969 or jennifer_higgins@cooley-dickinson.org.