Thomas A. Cavalieri, DO, professor and chair, Department of Medicine, and founding director, Center for Aging, UMDNJ-School of Osteopathic Medicine (SOM); and Anita Chopra, MD, professor of medicine and director of the Center for Aging at SOM

Historically certain groups have been excluded from participating in clinical research, either intentionally or by default. For example, from the late 1970s to the mid-1990s, in an effort to protect them from exploitation and harm, participation by women and children was limited to low risk research, a situation that NIH policy has since attempted to rectify. Less explicitly, a lack of insurance has also tended to affect a patient’s participation in clinical research, a situation that has been cited as a reason for exclusion of the elderly. An executive order by President Bill Clinton regarding Medicare coverage and medical expenses associated with clinical trials has attempted to rectify this inequity. However, the elderly continue to be underrepresented in clinical trials. Since they haven’t been deliberately excluded from clinical trials, nor encouraged to participate, the real reasons for this underrepresentation remain elusive and complicated.

A myriad of factors contribute to both the lack of referrals of elderly patients to clinical trials and their refusal to consent. Apprehension on the part of providers regarding the effects of aging, and/or aging physiology, on drug metabolism, and the existence of co-morbidities discourage participation, as do the patients’ fears of potential side effects, possible adverse drug interactions, and reduced quality of life. Issues such as frailty and competency come into play and a focus on chronological age rather than physiological age confounds recruitment. While concerns about practical matters such as lack of transportation and access, or social and home care support, may not be routinely considered in the recruitment of younger subjects, they may play a role in the recruitment of the elderly.

This underrepresentation is a concern because people older than 65 represent more than 12% of the total U.S. population today and these numbers will more than double by 2030. The elderly also utilize a disproportionate amount of healthcare resources. Expenditures for someone 65 years or older are now three to five times greater than for someone younger than 65. Most older people have at least one chronic condition and many have co-morbidities that result in additional medication use in general, as well as multiple medication regimens, and an increase in adverse drug interactions. It would seem imperative that the safety and efficacy of the drugs that will be used by the elderly be tested in the elderly.

A survey of the American pharmaceutical industry indicates that more than 800 medicines are currently in development for diseases of aging. The Center for Aging and SOM’s Department of Medicine are working collaboratively to support this effort. We will address the need to identify new medications that can safely and effectively improve the health and quality of life of America’s seniors.

We are conducting numerous clinical trials on Alzheimer’s disease (AD) and dementia, including a current study related to the treatment of cognitive function and global function in men with mild to moderate AD. This double-blind, placebo-controlled study will assess the safety and efficacy of a 48-week regimen of the drug leuprolide acetate. The study population includes non-institutionalized males 65 years or older with mild to moderate AD. The total number of patients enrolled is approximately 90, with 30 subjects randomized to each of three treatment groups: leuprolide acetate (22.5 mg per 12 weeks); leuprolide acetate (33.75 mg per 12 weeks); and placebo.

Leuprolide acetate, which is manufactured by Voyager Pharmaceutical Corporation, is administered at 12-week intervals. Patients randomized to placebo are receiving two placebo injections per 12 weeks. Safety assessments include vital signs, laboratory tests and queries about adverse events. Blood levels of testosterone and PSA will be monitored. Efficacy assessments include: Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL); ADCS-Clinical Global Impression of Change (ADCS-CGIC) (rating of change severity) performed at baseline and final visits only; and Burden Interview. Additional measures will also be taken. Patients were pooled from our existing patient base and through referral sources and outreach efforts.

Another study currently in progress examines the contribution of moderate to severe leukoaraiosis to the neuropsychological and instrumental activities of daily living deficits in patients with AD. Current Alzheimer’s disease studies are conducted in conjunction with Janssen Pharmaceutica Products, L.P., Easai, Inc., Eli Lilly and Company, and Bayer Pharmaceuticals Corporation.

The primary prevention of cardiovascular events in elderly patients with low levels of LDL cholesterol and elevated levels of C-reactive protein are being investigated in another clinical trial supported by AstraZeneca Pharmaceuticals, L.P. Of the roughly 64.4 million Americans with one or more types of cardiovascular disease, 25.3 million are estimated to be older than 65. In 2004, cardiovascular disease accounted for approximately $368.4 billion in estimated direct and indirect costs nationally. Cardiovascular disease has been the number one killer in the nation every year since 1900, except 1918. It claims more lives each year than the next five leading causes of death, at the rate of about one death every 34 seconds. Eighty-four percent of cardiovascular-related deaths are in people 65 and older.

As new drugs aimed at enhancing the quality of life in the later years emerge, we will be ready to participate in the clinical investigations necessary to facilitate the drugs’ availability to promote successful aging in the patients we serve.

Thomas A. Cavalieri, DO, FACOI, FACP, is professor of medicine and chair of the Department of Medicine at SOM. He is the former (founding) director of the Center for Aging. His research interests focus on end-of-life and ethical issues. Dr. Cavalieri has provided leadership to numerous state and federal committees. He currently serves as vice chair of the Advisory Committee on Interdisciplinary, Community-Based Linkages for the Health Resources and Services Administration. Dr. Cavalieri is also president of the American College of Osteopathic Internists. He has been recognized as one of the area’s “Top Docs” in Philadelphia Magazine, Consumer Union Checkbook, New Jersey Monthly, and South Jersey Magazine.

Anita Chopra, MD, FACP, is a professor of medicine at SOM as well as the director of the Center for Aging. She is also director of the New Jersey Geriatric Education Center and co-director of the geriatric medicine, dentistry and psychiatry fellowship program. Dr. Chopra is president of the New Jersey Medical Directors Association and serves on the board of directors for the Alzheimer’s Association Delaware Valley Chapter, Senior Citizens United Community Services, Promise Alternative Day Care Center, and New Jersey Geriatric Society. She has been recognized as one of the area’s “Top Docs” in Philadelphia Magazine and South Jersey Magazine. §