NCCAM's Centers of Excellence: Focusing on the Big--and (Very) Small--Picture
The National Institutes of Health (NIH) is the Nation's medical research agency--making medical discoveries to improve people's health, save lives, and reduce the burdens of illness and disability. As NIH's lead agency for research on complementary and alternative medicine (CAM), NCCAM shares in this pursuit of scientific discovery by supporting research studies on CAM at medical and scientific institutions throughout the United States.
Centers Pursue Topics in Depth
An important piece of NCCAM's extramural research program consists of 21 centers of research at leading medical and scientific institutions. The Research Centers Program is intended to build long-term programs that use expertise from a variety of disciplines, integrate research efforts from the laboratory bench to human studies, and develop and refine research methods and resources.
The Centers of Excellence for Research on CAM (CERCs) represented 9.1 percent of NCCAM's total budget for research in fiscal year 2006. In this issue, CAM at the NIH presents a closer look at the eight CERCs.
What Is a CERC?
Each NCCAM CERC:
- Has a grant that is 5 years long.
- Is pursuing three to four major projects that are related to each other and have a common theme--one or more CAM therapies (and/or themes important in CAM, such as wellness or the placebo effect) and one or more diseases or conditions that are a major health burden in the United States.
- Has a principal investigator highly skilled and experienced in research.
- Focuses on understanding "mechanisms of action"--in other words, how a CAM therapy works at the level of molecules, cells, and systems (for example, in animals). Some CERCs also conduct phase I or phase II clinical trials. In studies of substances like herbs, there may also be laboratory studies on characterization (to improve understanding of the substance's chemical composition), standardization (to improve the consistency of products in studies), and related topics.
- Is "synergistic"--that is, "the whole" (the results of the entire CERC program) is expected to be greater than "the sum of the parts" (the results of individual studies).
- Cuts across disciplines and is collaborative.
- Uses advanced research tools and techniques.
Says Acting NCCAM Director Ruth L. Kirschstein, M.D., "The CERC program is a key part of NCCAM's efforts to build and sustain research capacity across the Nation. Each CERC has put together a program in which several studies add to and play off of one another, and the collaborative approach helps create even more opportunities for discovery."
The following are snapshots of work being done at each of these centers.
Antioxidants for Lou Gehrig's Disease, Heart Disease, and Aging
Balz Frei, Ph.D.
Principal investigator: Balz Frei, Ph.D., director and endowed chair, Linus Pauling Institute, and professor of biochemistry and biophysics, Oregon State University, Corvallis.
Dr. Frei was personally touched by Lou Gehrig's disease, also called ALS (amyotrophic lateral sclerosis), when a good friend died of it at a young age. Lou Gehrig's disease attacks the nerve cells responsible for control of voluntary muscles. The patient's muscles gradually weaken and waste away, although his senses (and, in most cases, his mental abilities) are not impaired. Dr. Frei and his colleagues study antioxidants as possible future therapies for Lou Gehrig's and heart disease, and to possibly counteract the effects of human aging.
An antioxidant is a substance that protects cells from the damage caused by free radicals (unstable molecules made by a process of oxidation during normal metabolism). This process of damage, called oxidative stress, may play a part in certain diseases (including Lou Gehrig's disease and heart disease) and in aging.
The team is studying several antioxidants--including alpha-lipoic acid (also called lipoic acid), vitamin C, and vitamin E. The hope, Dr. Frei says, is that "we can better target treatment and eventually move the work into human studies"--first on heart disease and later on ALS and aging. He adds, "The CERC has been a great vehicle for our institute to bring people together, enhance interactions and collaborations, involve students, and move us to 'the next level.'"
An Herbal Formula for Asthma
Xiu-Min Li, M.D.
Principal investigator: Xiu-Min Li, M.D., associate professor of pediatric allergy/immunology, Mount Sinai School of Medicine, New York, New York.
Dr. Li and her colleagues are studying a three-herb Chinese formula called ASHMI as a therapy for asthma. ASHMI, which was developed at Mount Sinai, is based on a formula that Dr. Li was familiar with from her practice of medicine in China. Dr. Li notes that there is not yet any effective therapy for persistent, severe asthma, nor any way to prevent it. Also, while conventional therapies can be helpful for many asthma patients, she says, corticosteroids (the cornerstone of treatment) often cause serious side effects and, if the medication is stopped, worsen the disease.
This CERC's three studies are looking at the mechanism of action of ASHMI in an animal model, finding out more about its active components, and investigating it in phase I and phase II clinical trials. So far, the team has found that ASHMI has broad therapeutic actions on multiple asthma-related mechanisms in an animal model, and that the effects are long lasting. They have almost completed their phase I study and are moving toward a proposed phase II clinical trial. "The beauty of a CERC," says Dr. Li, "is that we have three independent but highly interactive projects and experts from many fields. Studying and developing a first-generation botanical drug is a very big project."
MBSR Meditation in Early Stage HIV
Principal investigator: Susan Folkman, Ph.D., director, Osher Center for Integrative Medicine, professor of medicine and Osher Foundation distinguished professor of integrative medicine, University of California, San Francisco, School of Medicine.
© Krzysztof Chrystowski
Physicians faced with a patient who has been diagnosed with early-stage HIV (the virus that causes AIDS) are in an uncertain position. Anti-HIV drugs are typically used only once the disease has advanced; it is not clear what, if anything, should be recommended to maintain immune function in earlier stages. Dr. Folkman and her colleagues hope to help change that situation by studying whether a type of meditation can benefit people in early stage HIV and improve their ability to cope with the stress of the disease. The researchers' work is based on prior studies showing that stress and depression are linked to the progression of HIV disease.
The research group's "Staying Well" study is a large, randomized, controlled trial on whether mindfulness-based stress reduction (MBSR) meditation can slow the progression of HIV, delay the need to start anti-HIV drugs (which have difficult side effects), and help participants with depression and quality of life. The control group attends an educational session covering many topics on living with HIV. Two related projects are examining the effects of MBSR on biological structures and processes, especially on the autonomic nervous system, secretion of the stress hormone cortisol, and immune system function.
"The CERC grant has greatly expanded our capacity to do research (including through infrastructure support), train researchers, and attract additional grant support," says Dr. Folkman. "We've had to wrestle with the question of 'what's a good comparison group?' for a mind-body therapy in which blinding is not possible, and I think we have one. When we do a clinical study at the Osher Center now, we also develop hypotheses about how the effects may be happening and test them. I think this should be the standard--not just in CAM, but in all clinical research, when possible."
CAM Therapies for Alcohol and Drug Abuse
Principal investigator: David Yue-Wei Lee, Ph.D., director, Bio-organic and Natural Products Laboratory, McLean Hospital, Belmont, Massachusetts, and associate professor of psychiatry, Harvard Medical School. (This CERC is cofunded by the National Institute on Alcohol Abuse and Alcoholism.)
"It's a huge problem; it's the tip of the iceberg, and there's no cure." So Dr. David Lee sums up what has compelled him to turn a doctoral degree in natural products chemistry, an interest in Chinese herbal medicine, and the resources of Harvard's McLean Hospital toward a very challenging health problem: drug and alcohol abuse.
Addiction problems will cost the United States an estimated $426 billion in 2007, says Dr. Lee. There is no uniformly effective treatment for drug and alcohol abuse, and the small number of prescription drug treatments available have side effects and a low success rate. Could two herbal remedies developed in China to treat opium smoking and alcohol intoxication be helpful? Dr. Lee and his colleagues are seeking to answer this question.
Kudzu (Pueraria lobata) is a primary ingredient of the Chinese herbal formula XJL (NPI-028).
© Alternative Nature Herbals
One of the herbal formulas, YGT (NPI-025), was developed because of a crisis that began in the mid-19th century in China, during which it is estimated that many millions of Chinese people became addicted to opium. Dr. Lee's team is also testing a traditional formula called XJL (NPI-028) to treat alcohol intoxication, and a device that delivers electrical stimulation to acupuncture points on the hand and wrist. The device has been successfully used in China as a combination treatment with herbal remedies.
The therapies are being studied on several levels: in a laboratory study on brain receptors, in animal models of alcohol and drug addiction, in a preclinical evaluation of the electrical device, and in future clinical studies. Dr. Lee says, "This packaged approach of a CERC grant works well for us, step by step, and has facilitated close working relationships within our group and with collaborators," including at Temple University, the University of North Carolina, and a national botanicals institute in China.
Millimeter Wave Therapy
Dr. Ziskin works with participant Ashok Bhanushali in a study of millimeter wave therapy for hypoalgesia.
Principal investigator: Marvin C. Ziskin, M.D., professor of radiology and director of the Center for Biomedical Physics, Temple University School of Medicine, Philadelphia.
Millimeter wave (MW) therapy is part of the CAM domain of energy medicine. It is based on a technology originally developed in the Soviet Union, during the Cold War, for military purposes. For health purposes, a MW device delivers a low-intensity electromagnetic beam to the skin at targeted points (for example, at an acupuncture point or a painful joint). The beam is absorbed by the skin at a shallow level.
MW therapy has been used in Eastern Europe for over 30 years to treat a wide variety of conditions, including skin diseases, wound healing, certain cancers, and gastrointestinal and cardiovascular diseases. "Reports of benefit have been mostly in the Russian literature," says Alexander Radzievsky, M.D., Ph.D., research assistant professor at Temple. "Hypoalgesia [lessened pain response], immunomodulation [activation or suppression of the immune system], and stimulation of repair are among its most important reported biological effects." He adds that a lack of quantitative study and/or blinding in past research and of precise explanations about the therapy are two reasons it is largely unknown in Western medicine.
This CERC is seeking to evaluate the biological effects of MW exposure, find the mechanisms of action, and develop strict indications for treatment. MW therapy is being studied in animal models for chronic neuropathic pain and pruritus (intense itching). "Chronic neuropathic pain, as one might have from an injury to the nerves or as a complication of diabetes, is very difficult to manage medically," says Dr. Radzievsky. "Sometimes even morphine or morphine-containing drugs don't help. MW therapy might offer another option. We hope our results will provide an appropriate theoretical basis for future clinical use. So far, the results have been very promising."
CAM Approaches for Arthritis
Coprincipal investigators: Brian Berman, M.D., professor and director, and Lixing Lao, Ph.D., L.Ac., associate professor and director of traditional Chinese medicine research, Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore.
Dr. Berman is leading a team studying approaches from traditional Chinese medicine for treating arthritis. They are partnering in this endeavor with colleagues at McLean Hospital and the University of Illinois at Chicago. This CERC is preparing to conduct a clinical trial on HLXL, a traditional Chinese formula made up of 11 herbs, to treat osteoarthritis of the knee. They are also exploring HLXL's mechanism of action.
Dr. Berman says, "Arthritis is a big problem in our society, especially in the elderly. There is no cure, and conventional treatments to manage it can have issues for many people. We're trying to find out whether this formula could potentially offer another option." He adds, "The grant is also giving us the opportunity to meet the challenges involved in a clinical trial of an herbal formula--such as addressing quality control and quality assurance, developing a convincing placebo, and preparing an Investigational New Drug application for the Food and Drug Administration." In addition, this CERC is conducting two mechanism-of-action studies: on acupuncture to treat inflammatory pain and on HLXL to treat rheumatoid arthritis.
Acupuncture and Brain Activity
Bruce Rosen, M.D., Ph.D.
© Bob Stockfield
Principal investigator: Bruce Rosen, M.D., Ph.D., director, Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, and professor of radiology, Harvard Medical School, Boston.
Dr. Rosen and his colleagues are working to increase knowledge of the possible pathways and circuitries in the brain involved in the effects of acupuncture. They are using functional magnetic resonance imaging (fMRI), a noninvasive neuroimaging technique used to observe the brain's functioning by detecting changes in oxygen content in the blood flowing to different brain regions. Their projects include:
- Characterizing the brain's response to acupuncture stimulation
- Studying acupuncture-induced sensation
- Exploring acupuncture's effects on the brain's response to amphetamine
- Defining parts of the brain involved in expectancy and the placebo effect in acupuncture.
"By looking directly into the brains of our subjects as they receive acupuncture, we can begin to tease out the complex mechanisms that underlie this ancient therapy," says Dr. Rosen. "With better understanding, we can then better design treatments that take advantage of acupuncture's unique properties." Currently, they are beginning to apply their findings in conditions such as arthritis and carpal tunnel syndrome (CTS). Results of preliminary studies, Dr. Rosen says, suggest that acupuncture can not only improve symptoms in CTS, but also affect objective measures of nerve function at the wrist and CTS-affected circuitry in the brain.
Antioxidants for Asthma
Principal investigator: David B. Peden, M.D., M.S., professor of pediatrics, medicine, and toxicology, and director of the Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina School of Medicine, Chapel Hill.
This CERC is conducting bench-to-bedside research on antioxidant CAM therapies for asthma. In the laboratory, Dr. Peden and his colleagues are seeking to understand the mechanisms of action and the effects of antioxidants that are vitamins and compounds derived from soy and red wine. In clinical studies, they will attempt to discover whether these treatments can decrease inflammation of the airway in response to common asthma triggers, such as ozone or inhaled allergens. One of the current clinical studies is on gamma tocopherol, a naturally occurring form of vitamin E that is found in many foods and is also manufactured as a supplement.
You can read more on these CERCs' grants by searching the CRISP database and on published results to date by searching the PubMed database.
