Scientific research is a long-term investment with the goal of improving public health and health care. Over the last 20 years, NCCIH has invested in numerous clinical trials, which were built upon countless previous scientific investigations. Here we look back at a few of these trials and evaluate the impacts of those investments.
The AREDS trials: The Age-Related Eye Disease Study (AREDS) began in 1992, before NCCIH was created. This clinical trial was sponsored by the National Eye Institute (NEI) and sought to evaluate the effects of a nutritional supplement, called the AREDS formulation, on the progression of age-related macular degeneration (AMD). AMD is one the leading causes of visual impairment and blindness in the United States. The results from this study were published in 2001 and showed that the AREDS formulation significantly reduced the risk of advanced AMD and its associated vision loss. These results were exciting and represented the first intervention shown to reduce the risk of advanced AMD. The AREDS formulation contains high doses of vitamin C, vitamin E, beta-carotene, and zinc, and while it was shown to be effective there were concerns about the high concentration of beta-carotene. Other studies completed while AREDS was in progress showed that high concentrations of beta-carotene were associated with an increased risk of lung cancer in smokers. So in 2006, a second clinical trial, called AREDS2, was launched to determine if the AREDS formulation could still be effective if beta-carotene was removed. NCCIH contributed approximately $1.5 million to this study. The effort was led by NEI and received additional funds from other NIH Institutes. In the AREDS2 trial, the antioxidants lutein and zeaxanthin, which are in the same family of nutrients as beta-carotene, were added to the AREDS formulation as a substitute for beta-carotene. The study found that lutein and zeaxanthin together appeared to be a safe and effective alternative to beta-carotene. The scientific investments made in the AREDS trials helped identify nutritional supplements that reduced the risk of developing advanced stages of AMD by about 25 percent and the risk of central vision loss by 19 percent in people with high risk of developing the disease. The AREDS and AREDS2 formulations have undergone phase 3 clinical trials and are available over the counter in the United States.
The TACT trials: The Trial to Assess Chelation Therapy (TACT) began in 2002. This clinical trial was sponsored by NCCIH and the National Heart, Lung, and Blood Institute (NHLBI). The trial sought to determine the safety and efficacy of disodium EDTA (ethylene diamine tetra-acetic acid) chelation therapy in individuals with coronary artery disease–the leading cause of death for both men and women in the United States. Chelation is a chemical process where a substance is used to tightly bind metals or minerals. The FDA has approved chelation with EDTA for the treatment of lead poisoning or exposure to other heavy metals. Before the TACT clinical trial, some physicians and alternative medicine practitioners were recommending EDTA chelation as a complementary treatment for heart disease, without evidence to support its safety or efficacy and sometimes in lieu of proven conventional therapies. The 5-year TACT study was designed to determine if this practice was safe and effective. The results of this study showed EDTA chelation therapy resulted in a modest reduction in cardiovascular events overall. However, among participants with diabetes there was an impressive 41 percent reduction in the risk of any cardiovascular event; a 52 percent reduction in recurrent heart attacks; and a 43 percent reduction in death from any cause. In 2016, NCCIH, NHLBI, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Environmental Health Sciences (NIEHS) supported a large follow-up study. The goal of this study, called TACT2, was to repeat the results of the first TACT study–but only in patients with diabetes and a prior heart attack–to see if the apparent benefit could be replicated. It is anticipated that the TACT2 phase 3 clinical trial will be complete in FY 2023. In total, NCCIH has invested approximately $54.9 million in the TACT trials. This scientific investment will help the FDA determine whether disodium EDTA chelation therapy should be an approved intervention to reduce the risk of further cardiovascular events in patients with both coronary artery disease and diabetes.
The cytisine trials: In 2015, NCCIH started a public-private partnership with Achieve Life Sciences, Inc., to advance clinical trials of cytisine, a natural product for smoking cessation. Cytisine is isolated from the plant Laburnum anagyroides and has been used as a smoking cessation aid, primarily in eastern European countries, for several decades. Cytisine clinical trials conducted outside of the United States showed promise in helping participants stop smoking, but those studies did not conform to U.S. FDA standards. Clinical trials needed to be conducted under Investigational New Drug (IND) guidelines before cytisine could be made available in the United States. Achieve Life Sciences, Inc., was interested in bringing cytisine to the United States but was struggling to find private investment to support the preclinical safety and toxicology studies needed to begin U.S. clinical trials. NCCIH decided to help Achieve Life Sciences, Inc., overcome this bottleneck, supported the necessary preclinical trials, and used the NIH Blueprint Neurotherapeutic Network to conduct the studies. This approximate $1.7 million investment enabled FDA acceptance of the IND application for cytisine and made it possible for Achieve Life Sciences, Inc., to begin clinical trials and raise private funds to conduct them. Since 2015, Achieve Life Sciences, Inc., has successfully completed a phase 2b clinical trial. The company plans to begin the phase 3 clinical trial in 2021 to complete its New Drug Application to the FDA. These investments may lead to the wide availability of a new smoking cessation option to address the major public health issues associated with tobacco use.