The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010.

Background

The overall prevalence of complementary medicine (CM) use among adults in the United States with diabetes has been examined both in representative national samples and in more restricted populations. However, none of these earlier studies attempted to identify predictors of CM use to treat diabetes among the populations sampled, nor looked for a relationship between CM use and diabetes severity.

Methods

Combining data from the 2002 and 2007 National Health Interview Survey (NHIS), we constructed a nationally representative sample of 3,978 U.S. adults aged ≥18 years with self-reported diabetes. Both the 2002 and 2007 NHIS contained extensive questions on the use of CM. We used logistic regression to examine the association between diabetes severity and overall CM use, as well as the use of specific categories of CM.

Results

In adults with type-2 diabetes, 30.9% used CM for any reason, but only 3.4% used CM to treat or manage their type-2 diabetes versus 7.1% of those with type-1 diabetes. Among those using CM to treat/manage their type-2 diabetes, 77% used both CM and conventional prescription medicine for their diabetes. The most prevalent types of CM therapies used were diet-based interventions (35.19%, S.E. 5.11) and non-vitamin/non-mineral dietary supplements (33.74%, S.E. 5.07). After controlling for sociodemographic factors, we found that, based on a count of measures of diabetes severity, persons with the most severe diabetes had nearly twice the odds of using CM as those with less severe disease (OR=1.9, 95%CI 1.2-3.01). Persons who had diabetes 10 years or more (OR=1.66, 95%CI 1.04-3.66) and those that had a functional limitation resulting from their diabetes (OR=1.74, 95%CI 1.09-2.8) had greater odds of using CM than those not reporting these measures. No significant associations were observed between overall CM use and other individual measures of diabetes severity: use of diabetic medications, weak or failing kidneys, coronary heart disease, or severe vision problems.

Conclusions

Our results demonstrate that individuals with more severe diabetes are more likely to use CM independent of sociodemographic factors. Further studies are essential to determine if CM therapies actually improve clinical outcomes when used to treat/manage diabetes.

Abstract

In October 2007, a National Center for Complementary and Alternative Medicine (NCCAM)–sponsored workshop, entitled “Applying Principles from Complex Systems to Studying the Efficacy of CAM Therapies,” was held at Georgetown University in Washington, DC. Over a 2-day period, the workshop engaged a small group of experts from the fields of complementary and alternative medicine (CAM) research and complexity science to discuss and examine ways in which complexity science can be applied to CAM research. After didactic presentations and small-group discussions, a number of salient themes and ideas emerged. This paper article describes the workshop program and summarizes these emergent ideas, which are divided into five broad categories: (1) introduction to complexity; (2) challenges to CAM research; (3) applications of complexity science to CAM; (4) CAM as a model of complexity applied to medicine; and (5) future directions. This discusses possible benefits and challenges associated with applying complexity science to CAM research. By providing an introductory framework for this collaboration and exchange, it is hoped that this article may stimulate further inquiry into this largely unexplored area of research.

Purpose

Evidence from in vitro and in vivo studies suggests that Ginkgo biloba has cancer chemopreventive properties, but epidemiological evidence is sparse. We analyzed cancer as a secondary endpoint in the Ginkgo Evaluation of Memory (GEM) Study, the largest randomized, double-blind, placebo-controlled clinical trial of Ginkgo supplementation to date.

Methods

A total of 3,069 GEM participants 75+ years of age were randomized to twice-daily doses of either 120mg Ginkgo extract (EGb 761) or placebo and followed for a median 6.1 years. We identified hospitalizations for invasive cancer by reviewing hospital admission and discharge records for all reported hospitalizations over follow-up. Using an intention-to-treat approach, we compared the risk of cancer hospitalization between participants assigned to treatment and those assigned to placebo.

Results

During the intervention, there were 148 cancer hospitalizations in the placebo group and 162 in the EGb 761 group (Hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.87–1.36; p=0.46). Among the site-specific cancers analyzed, we observed an increased risk of breast (HR, 2.15; 95% CI, 0.97–4.80; p=0.06) and colorectal (HR, 1.62; 95% CI, 0.92–2.87; p=0.10) cancer, and a reduced risk of prostate cancer (HR, 0.71; 95% CI, 0.43–1.17; p=0.18).

Conclusions

Overall, these results do not support the hypothesis that regular use of Ginkgo biloba reduces the risk of cancer.

Background

Accumulating evidence suggests that ginkgo biloba is cardioprotective, in part, through its vasodilatory and antihypertensive properties. However, definitive data on its blood pressure-lowering effects in humans is lacking.

Methods

We determined the effects of ginkgo biloba extract (240 mg/day) on blood pressure and incident hypertension in 3,069 participants (mean age, 79 yrs; 46% female; 96% White) from the Ginkgo Evaluation of Memory study. We also examined whether the treatment effects are modified by baseline hypertension status.

Results

At baseline 54% of the study participants were hypertensive, 28% were pre-hypertensive, and 17% were normotensive. Over a median follow-up of 6.1 years, there were similar changes in blood pressure and pulse pressure in the ginkgo biloba and placebo groups. Although baseline hypertension status did not modify the antihypertensive effects of ginkgo biloba, it did influence the changes in blood pressure variables observed during follow-up, with decreases in hypertensives, increases in normotensives, and no changes in pre-hypertensives. Among participants who were not on antihypertensive medications at baseline, there was no difference between treatment groups in medication use over time, as the OR (95% CI) for being a never-user in the ginkgo biloba group was 0.75 (0.48–1.16). The rate of incident hypertension also did not differ between participants assigned to ginkgo biloba vs. placebo (HR, 0.99, 95% CI, 0.84–1.15).

Conclusions

Our data indicate that ginkgo biloba does not reduce blood pressure or the incidence of hypertension in elderly men and women.

Background

We hypothesize that a substantial portion of individuals who forgo conventional care in a given year turn to some form of alternative medicine. This study also examines whether individuals who use only alternative medicine will differ substantially in health and sociodemographic status from individuals using neither alternative medicine nor conventional care in a given year. To identify those factors that predict alternative medicine use in those not using conventional care, we employed the socio-behavioral model of healthcare utilization.

Methods

The current study is a cross-sectional regression analysis using data from the 2002 National Health Interview Survey. Data were collected in-person from 31,044 adults throughout the 50 states and the District of Columbia.

Results

19.3% of adults (38.3 million) did not use conventional care in a 12 month period, although 39.5% of these individuals (14.7 million) reported having one or more problems with their health. Of those not using conventional care, 24.8% (9.5 million) used alternative medicine. Users of alternative medicine had more health needs and were more likely to delay conventional care because of both cost and non-cost factors compared to those not using alternative medicine. While individual predisposing factors (gender, education) were positively associated with alternative medicine use, enabling factors (poverty status, insurance coverage) were not.

Conclusions

We found that a quarter of individuals who forgo conventional care in a given year turn towards alternative medicine. Our study suggests that the potential determinants of using only alternative medicine are multifactorial. Future research is needed to examine the decision process behind an individual's choice to use alternative medicine but not conventional medicine and the clinical outcomes of this choice.

The NIH sponsored a scientific workshop, “Soy Protein/Isoflavone Research: Challenges in Designing and Evaluating Intervention Studies,” July 28–29, 2009. The workshop goal was to provide guidance for the next generation of soy protein/isoflavone human research. Session topics included population exposure to soy; the variability of the human response to soy; product composition; methods, tools, and resources available to estimate exposure and protocol adherence; and analytical methods to assess soy in foods and supplements and analytes in biologic fluids and other tissues. The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy. Prior NIH workshops and an evidence-based review questioned the quality of data from human soy studies. If clinical studies are pursued, investigators need to ensure that the experimental designs are optimal and the studies properly executed. The workshop participants identified methodological issues that may confound study results and interpretation. Scientifically sound and useful options for dealing with these issues were discussed. The resulting guidance is presented in this document with a brief rationale. The guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies. This guidance may be used by investigators, journal editors, study sponsors, and protocol reviewers for a variety of purposes, including designing and implementing trials, reporting results, and interpreting published epidemiological and clinical studies.

Background

Surveys have generally found that individuals more likely to use complementary and alternative medicine are female, live in the western United States, are likely to have a health complaint, and have a higher socioeconomic status than do nonusers. What is not known is the extent to which those who use complementary and alternative medicine also engage in positive health behaviors, such as smoking cessation or increased physical activity and/or exhibit fewer health risk factors such as obesity. This has been identified as a key research question in a recent Institute of Medicine report. In the present study we sought to determine whether the use of complementary and alternative medicine is associated with health behaviors or risk factors known to impact on health status.

Methods

The current study is a cross-sectional regression analysis using data from the 2002 National Health Interview Survey. Data were collected in-person from 31,044 adults throughout the 50 states and the District of Columbia.

Results

After controlling for a range of other factors, we found that engaging in leisure-time physical activity, having consumed alcohol in one's life but not being a current heavy drinker, and being a former smoker are independently associated with the use of CAM. Obese individuals are slightly less likely to use CAM than individuals with a healthy body-mass index. No significant associations were observed between receipt of an influenza vaccine and CAM use.

Conclusion

Those engaging in positive health behaviors and exhibiting fewer health risk factors are more likely to use CAM than those who forgo positive health behaviors or exhibit more health risk factors. The fact that users of CAM tend to pursue generally healthy lifestyles suggests that they may be open to additional recommendations toward optimizing their health.

Context

Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G biloba on dementia incidence are lacking.

Objective

To determine effectiveness of G biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI).

Design, Setting, and Participants

Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n=2587) or MCI (n=482) at study entry were assessed every 6 months for incident dementia.

Intervention

Twice-daily dose of 120-mg extract of G biloba (n=1545) or placebo (n=1524).

Main Outcome Measures

Incident dementia and AD determined by expert panel consensus.

Results

Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94–1.33; P=.21) and for AD, 1.16 (95% CI, 0.97–1.39; P=.11). G biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85–1.50; P=.39).

Conclusions

In this study, G biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI.