Researchers investigate if drug for leg cramps can prevent a second stroke

A second ischemic stroke, the most common stroke type, is associated with double the risk of death and triple the risk of long-term disability. A drug that has shown effectiveness in patients in Japan and China may change these odds. 

Next week, UC San Francisco will start enrolling patients in a study that uses cilostazol, a drug approved to treat leg cramping and numbing in patients with peripheral artery disease. Researchers hope that cilostazol will cut stroke recurrence by 50%.

Stroke is the fourth leading cause of death in the United States, and approximately 87% of strokes are ischemic, which affects between 1 in 6 to 1 in 7 Americans. 

The trial is funded by the National Institute of Neurological Disorders and Stroke (NINDS) and is open to patients diagnosed within the last six months with an ischemic stroke or high-risk transient ischemic attack (TIA). Both conditions are caused by a blood clot or narrowing of an artery, restricting the flow of oxygenated blood to the brain. 

After a first stroke, the brain relies on neuroplasticity to use surrounding tissue to rewire undamaged brain networks to take over lost functions, like movement and speech. With a second stroke, these newly recruited pathways may be further damaged, leading to fewer healthy nerve cells. The brain loses its ability to compensate, making recovery slower and more challenging." 

Anirudh Sreekrishnan, MD, site principal investigator for the study and director, UCSF Stroke Clinic

Researchers hope to enroll more than 2,000 stroke patients from sites across the country. The study is conducted by NIH StrokeNet, a national research network for stroke prevention, acute treatment, and recovery. Anthony S, Kim, MD, medical director of the UCSF Comprehensive Stroke Center, is the principal investigator for the network's regional coordinating center and is responsible for trial execution and oversight at UCSF and partner StrokeNet sites. 

Principal investigators of the national trial are Adam de Havenon, MD, and Kevin Sheth, MD, of Yale, and Maarten Lansberg, MD, PhD, of Stanford. 

Can U.S. study duplicate Japan's success?

The U.S. researchers were galvanized by studies in Japan, China, and other East Asian countries. Notably, a 2019 study in Japan compared the effects of standard therapy, aspirin, or clopidogrel, which reduces recurrence by preventing blood from clumping and forming clots, to standard therapy plus cilostazol, which has the added advantage of protecting the lining of brain arteries without increasing the risk of brain bleeds.

The study found that within four years of a stroke, 11.4% of patients on standard therapy experienced a subsequent stroke versus 4.7% for those who added cilostazol. Prevalence of side effects, including serious bleeding, was similar for both groups

However, unlike the upcoming StrokeNet study, the Japanese study was not a double-blinded placebo trial, in which neither doctors nor patients know who is receiving treatment and who is receiving placebo. "Without this gold standard, there's the potential to introduce bias," said Kim. 

Additionally, "2 in 3 participants were male and all were Japanese," noted Sreekrishnan. "It is not yet known if this level of effectiveness can be replicated in the United States with its racially diverse population."

The study will be conducted at 100 sites throughout the U.S. and participants will be followed for up to five years. More information can be found at the StrokeNet Clarity Trial site.