When UConn professor William White asked Agnes Cuotto to be part of a study to test the effectiveness of a new cholesterol-lowering drug, she was eager to participate. Cuotto says she feels she is making a contribution to science and society.

“It’s wonderful to be in a study because you are constantly monitored and the doctors and nurses are paying special attention to you. It doesn’t take a lot of time and it’s worth it,” says Cuotto, 75, a retired school secretary who has both high cholesterol and hypertension. She has her blood pressure taken, blood drawn and urine tested three or four times a year as part of the study to see how far the drug Crestor has reduced her cholesterol.

Both Cuotto and her husband have been subjects in clinical trials—research studies that help to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to conclude the final stage of research before a drug or treatment can be approved for use in the general population.

Cuotto, who lives in Avon, Conn., has watched her total cholesterol count drop from more than 280 to under 200 (200 is considered normal). White, a professor of medicine at the UConn Health Center, is delighted that Cuotto’s low-density lipoprotein (bad cholesterol) has dropped from 160 to 100.

A drug like Crestor costs half a billion dollars to develop and can take a decade or more to go from the laboratory to the drugstore, says White. Before any drug goes to clinical trials, it has already been tested in animals and is ready for human testing.

Research and clinical trials may be funded by drug manufacturers, private nonprofit organizations such as the National Cancer Society, or government agencies such as the National Institutes of Health.

The Crestor study is just one of the 300 to 400 active clinical trials of drugs and treatments underway at the University of Connecticut at any given time. The topics of these clinical studies vary from compulsive gambling and alcohol abuse to cancer and alternative medicine, says Herbert Bonkovsky, director of UConn’s General Clinical Research Center.

“Our main goal is to relieve suffering and cure or ameliorate disease. That’s why we’re here. We’re trying to bring the most recent medical advances to the bedside. The only way to do this is by conducting well-designed clinical studies,” Bonkovsky says.

UConn is designated as a Carnegie Foundation Research University, which places it among a select group of only 4 percent of the nation’s higher education institutions. As the state’s only public research university, an essential element of UConn’s mission is to expand human knowledge in a variety of disciplines, including health care. The UConn Health Center has nearly 40 designated centers and departments dedicated to improving human health and patient care as well as to expanding the understanding of disease and working toward finding new ways to treat or cure illness and disease.

Clinical trials are done in phases. In phase I, the drug or treatment is tested in a small number of healthy people (20 to 80) to determine proper dosing and safety and to identify side effects. In phase II, the drug is given to a larger group of people (100 to 300) who have the condition (i.e., high cholesterol) to see if the treatment is safe and effective. Phase III enrolls from 1,000 to 3,000 people and looks at the study drug in comparison to a similar treatment for the condition. Finally, in phase IV trials researchers ask questions about the drug and how it interacts with other medications, such as how cholesterol-lowering drugs would act in a patient taking medications for hypertension and diabetes.

Alcohol abuse researcher Henry Kranzler, professor of psychiatry and associate scientific director of the Alcohol Research Center at the UConn Health Center, recently published the results of a phase III trial showing that monthly injections of the drug naltrexone helped alcoholics abstain from drinking and postpone heavy drinking.

Naltrexone reduces the pleasurable effects of alcohol. It was originally developed as a treatment for heroin addiction; it blocks the effects of narcotic-based drugs. The injections are more effective than oral tablets of naltrexone because patients cannot decide to stop their medication when they want to drink. When the medication is injected, it remains consistent in the patient’s blood for one month.

Kranzler says many alcoholic patients are eager to find help for their disease and are willing to participate in studies. Drugs are not routinely prescribed to fight alcoholism, and most problem drinkers seek assistance through Alcoholics Anonymous meetings or conventional psychotherapy. The use of drug therapy can help alcoholics move to ease their dependence on drinking because many patients feel that they are being treated with respect for the first time, instead of being ridiculed for their addiction, he says.

Complementary or alternative medicine is a growing trend in medical care. The federal government established the National Center for Complementary and Alternative Medicine in 1998 and has allocated $118 million in fiscal year ’04 for studies in areas such as meditation, acupuncture and herbal remedies.

At the UConn Center on Aging, Karen Prestwood is examining whether soy protein, with and without estrogen-like substances in plant protein, known as isoflavones, increases bone density in women in the beginning stages of osteoporosis. Estrogen therapy is a federally approved treatment for osteoporosis.

Illustration by Janet Atkinson

The year-long study, funded by the U.S. Department of Agriculture, measures bone mineral density in four groups of patients to determine the effectiveness of taking soy protein.

“The theory is that the whole food is the best thing for health,” says Prestwood. “Women are taking soy powder and isoflavone tablets, and this will give us an idea about whether the hypothesis is correct.” If this pilot study is correct, then another, larger trial will be done.

Carolyn Runowicz ’73 (CLAS), director of UConn’s Carole and Ray Neag Comprehensive Cancer Center, has been a principal investigator in many clinical trials of drugs to fight women’s cancers. One study is trying to determine if the drug OvaRex can prevent the recurrence of cancer in ovarian cancer patients. Runowicz would like to organize a statewide clinical trials network. She has already met with cancer researchers at some of the major programs in Connecticut, including Yale-New Haven Hospital and Hartford Hospital. Proposed clinical trials would test drugs to fight breast, colon, ovarian and lung cancers.

“In building this network, we are trying to bring state-of-the art treatments to the people of Connecticut,” Runowicz says. In one innovative new study, Zihai Li is looking at tumor biology and correlating it with treatment. Forty to 60 percent of ovarian cancer patients have a relapse of the disease, so by taking tissue from a patient’s tumor, Li and his team are trying to create a vaccine to prevent that specific ovarian cancer tumor from growing again.

Runowicz notes that nationally almost all pediatric cancer patients are enrolled in clinical trials, but only about 10 percent of adult patients participate. She says she would like UConn to meet or exceed having 10 percent of patients enlist in clinical trials.

Bonkovsky, the director of the UConn Health Center’s General Clinical Research Center, sums up the importance of clinical trials, saying “Clinical research is ‘where the rubber meets the road’; where the advances in basic biology and medicine are translated into the relief of human suffering and disease. Our efforts are important to every citizen of Connecticut—and of the wider world.”

This is a partial listing of the active clinical trials underway at the UConn Health Center. The list of trials changes as new studies begin and others conclude. For a complete list, go to following Web site: http://health.uchc.edu/clinicaltrials/index.asp

BEHAVIORAL
Depression: A multi-center study of differing doses of a medication to treat patients with major depressive disorder.

Schizophrenia: Comparing two marketed medications to treat schizophrenia and schizoaffective disorder in patients with weight and health problems.

Drug Dependence: Researchers are studying four different ways to treat heavy marijuana users.

Alcohol Dependence: A number of studies under way, including evaluating treatments for adolescents with problem drinking with or without accompanying substance abuse disorders.

Nicotine Dependence: Trying to determine whether nicotine gum is safe and if it helps women quit smoking in order to avoid serious pregnancy problems and increase the chance of having a healthy baby.

Compulsive Gambling: Reviewing therapy treatments for pathological gambling.

BONE METABOLISM
Osteoporosis: Examining the effect of the hormone estrogen on the cells that build and break down bone.

CANCER
Breast Cancer: Nine studies under way, including one to evaluate the safety and effectiveness of two chemotherapy drugs for advanced breast cancer. Another will determine if a new drug can reduce the recurrence of breast cancer.

Cervical Cancer: Testing whether injections of an investigational vaccine can stimulate the immune system to react with a certain type of human papillomavirus (HPV).

Colorectal Cancer: Two chemotherapy/radiation therapy treatments for rectal cancer to see positive results and what side effects, if any, the therapies produce.

Lung Cancer: Studying whether dietary supplementation with selenium, a normally occurring trace element in humans, will help prevent a recurrence of cancer following complete surgical removal of the tumor.

Melanoma: Three investigations are underway, including one for a drug based on a substance normally produced by the body’s immune system and used with early melanoma that is removed surgically.

Prostate Cancer: Four studies, including a pilot study of bone health in men over age 60 years who are receiving injections as treatment for prostate cancer.

CARDIOLOGY
Hypertension: Postmenopausal women ages 45-75 years are using a new hormone replacement therapy that may also help to lower blood pressure.

INFECTIOUS DISEASE
Adult HIV: A large trial that compares two strategies for management of anti-retroviral therapy.

ORAL DISEASES
Oral Mucositis: Testing the effectiveness of an investigational new drug to reduce the severity of mouth sores caused by radiation therapy.

RHEUMATIC DISEASES
Osteoarthritis: Determining the effectiveness of three injections of a viscosupplement in reducing pain and restoring function to anyone with osteoarthritis of the shoulder.

Scleroderma: Patients with painful finger ulcers are being studied to see whether a new medication will promote healing of the ulcer over a certain time period.

SURGERY
Angioplasty: Testing the safety and effectiveness of a drug in keeping the leg arteries open after a successful angioplasty in men and women 40 years of age or older who have been diagnosed with peripheral arterial disease.

OTHER
Anterior Cruciate Ligament: Seeking a possible cause of anterior cruciate ligament (ACL) tears in women by testing the looseness of the ACL and comparing it to hormone levels in the blood.

Chronic Bronchitis: Determining the safety and effectiveness of a high-dose, short-course of one drug in comparison with two other drugs in men and women at least 18 years of age who have an acute exacerbation of chronic bronchitis.

Hepatitis B: Using an experimental drug for chronic hepatitis B for patients who are resistant to other drugs and who have decompensated liver disease.

Parkinson’s Disease: Determining whether a new medication will help to delay or stop some types of cell death believed to be involved in the development of Parkinson’s Disease.