All Posts tagged trials

Placebos may work – even when the patient knows

For most of us, the “placebo effect” is synonymous with the power of positive thinking; it works because you believe you're taking a real drug. But a new study rattles this assumption.Researchers at Harvard Medical School's Osher Research Center and Beth Israel Deaconess Medical Center (BIDMC) have found that placebos work even when administered without the seemingly requisite deception.

Placebos—or dummy pills—are typically used in clinical trials as controls for potential new medications. Even though they contain no active ingredients, patients often respond to them. In fact, data on placebos is so compelling that many American physicians (one study estimates 50 percent) secretly give placebos to unsuspecting patients. Because such “deception” is ethically questionable, HMS associate professor of medicine Ted Kaptchuk teamed up with colleagues at BIDMC to explore whether or not the power of placebos can be harnessed honestly and respectfully.

To do this, 80 patients suffering from irritable bowel syndrome (IBS) were divided into two groups: one group, the controls, received no treatment, while the other group received a regimen of placebos—honestly described as “like sugar pills”—which they were instructed to take twice daily. “Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had 'placebo' printed on the bottle,” says Kaptchuk. “We told the patients that they didn't have to even believe in the placebo effect. Just take the pills.”

For a three-week period, the patients were monitored. By the end of the trial, nearly twice as many patients treated with the placebo reported adequate symptom relief as compared to the control group (59 percent vs. 35 percent). Also, on other outcome measures, patients taking the placebo doubled their rates of improvement to a degree roughly equivalent to the effects of the most powerful IBS medications. “I didn't think it would work,” says senior author Anthony Lembo, HMS associate professor of medicine at BIDMC and an expert on IBS. “I felt awkward asking patients to literally take a placebo. But to my surprise, it seemed to work for many of them.”

The authors caution that this study is small and limited in scope and simply opens the door to the notion that placebos are effective even for the fully informed patient—a hypothesis that will need to be confirmed in larger trials. “Nevertheless,” says Kaptchuk, “these findings suggest that rather than mere positive thinking, there may be significant benefit to the very performance of medical ritual. I'm excited about studying this further. Placebo may work even if patients knows it is a placebo.”

This study was funded by the National Center for Complementary and Alternative Medicine and Osher Research Center, Harvard Medical School.

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Replace Saturated Fat with Polyunsaturated Dat

Over the past several decades, the food industry has reduced the amount of saturated fat in many products, and the public has reduced the amount of saturated fat in their diet. However, there has been a wide variation in the types of nutrients that have replaced this saturated fat. For example, in many products saturated fats were replaced with trans fats, which have since been determined to be detrimental; and in the overall American diet saturated fat was generally replaced with increased consumption of refined carbohydrates and grains.

“The specific replacement nutrient for saturated fat may be very important,” said lead author Dariush Mozaffarian, assistant professor in the department of epidemiology at HSPH and the department of medicine at Harvard Medical School. “Our findings suggest that polyunsaturated fats would be a preferred replacement for saturated fats for better heart health.”

Results from prior individual randomized controlled trials of saturated fat reduction and heart disease events were very mixed, with most showing no significant effects. Other trials focused only on blood cholesterol levels, which are an indirect marker of risk. Large observational studies have also generally shown no relationship between saturated fat consumption and risk of heart disease events; for example, earlier this month in the American Journal of Clinical Nutrition, researchers from HSPH and Children's Hospital Oakland Research Institute performed a pooled meta-analysis of prior observational studies and found no evidence that overall consumption of saturated fat was related to risk of coronary heart disease or stroke events.

Some of these mixed findings may relate to absence of prior focus on the specific replacement nutrient for saturated fat; in other words, was saturated fat replaced primarily with carbohydrate, monounsaturated fats such as in olive oil, or polyunsaturated fats such as in most vegetable oils?

Mozaffarian and his HSPH colleagues, Renata Micha and Sarah Wallace, performed a systematic review and meta-analysis of all randomized controlled trials through June 2009 in which participants specifically increased their polyunsaturated fat consumption as a replacement for saturated fat and in which coronary heart disease events were documented. Eight trials met the inclusion criteria, totaling 13,614 participants with 1,042 coronary heart disease events.

The meta-analysis of the trials showed that increasing polyunsaturated fat consumption as a replacement for saturated fat reduced the risk of coronary heart disease events by 19%. For every 5% increase (measured as total energy) in polyunsaturated fat consumption, coronary heart disease risk was reduced by 10%. This is now just the second dietary intervention–consuming long-chain omega-3 fatty acids is the first — to show a reduction in coronary heart disease events in randomized controlled trials.

Currently, the Institute of Medicine guidelines recommend that a range of 5%-10% energy consumption come from polyunsaturated fats. In addition, some scientists and organizations have recently suggested that consumption of polyunsaturated fats (largely “omega-6” fatty acids) should actually be reduced due to theoretical concerns that such consumption could increase coronary heart disease risk.

The results from this study suggest that polyunsaturated fats from vegetable oils may be an optimal replacement for saturated fats, an important finding for dietary guidelines and for when food manufacturers and restaurants are making decisions on how to reduce saturated fat in their products. The findings also suggest that an upper limit of 10% energy consumption from polyunsaturated fats may be too low, as the participants in these trials who reduced their risk were consuming about 15% energy from polyunsaturated fats.

Support for this study was provided by the National Heart, Lung, and Blood Institute, NIH and a Searle Scholar Award from the Searle Funds at the Chicago Community Trust.

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Benefits of Calcium and Vitamin D

Led by researchers at Copenhagen University in Denmark, Robbins and an international team of colleagues analyzed the results of seven large clinical trials from around the world to assess the effectiveness of vitamin D alone or with calcium in reducing fractures among people averaging 70 years or older. The researchers could not identify any significant effects for people who only take vitamin D supplements.

Among the clinical trial results analyzed was Robbins' WHI research, which was part of a 15-year, national program to address the most common causes of death, disability and poor quality of life in postmenopausal women such as cardiovascular disease, cancer and osteoporosis. Those trials were primarily designed to study the effect of calcium and vitamin D supplementation in preventing hip fractures, with a secondary objective of testing the supplements on spine and other types of fractures, as well as on colorectal cancer. The results were published in the Feb. 16, 2006 edition of the New England Journal of Medicine.

Fractures are a major cause of disability, loss of independence and death for older people. The injuries are often the result of osteoporosis, or porous bone, a disease characterized by low bone mass and bone fragility. The National Osteoporosis Foundation estimates that about 10 million Americans have osteoporosis; 80 percent of them are women. Four of 10 women over age 50 will experience a fracture of the hip, spine or wrist in their lifetime, and osteoporosis-related fractures were responsible for an estimated $19 billion in health-related costs in 2005.

“This study supports a growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing a variety of fractures,” said Robbins. “Interestingly, this combination of supplements benefits both women and men of all ages, which is not something we fully expected to find. We now need to investigate the best dosage, duration and optimal way for people to take it.”

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