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South Florida researchers investigate if diabetes drug can prevent Alzheimer's

http://www.sun-sentinel.com/health/fl-alzheimers-drug-cleveland-trial-20140502,0,3192997.story

Takeda Pharmaceutical Co., based in Japan, is one of the manufacturers of the diabetes drug Actos, being tested for preventing Alzheimer's disease. (ARND WIEGMANN / REUTERS / April 8, 2014)

By Diane C. Lade, Staff writer
8:12 p.m. EDT, May 2, 2014

Is one of the most common chronic medical conditions among seniors connected to one of the most feared?

South Florida researchers have joined a worldwide clinical trial investigating whether a well-known medication for Type 2 diabetes could delay or prevent Alzheimer's disease, an incurable neurological condition affecting almost a half-million Floridians.

As part of what's called the TOMORROW study, Cleveland Clinic in Weston is looking to enroll 120 participants, ages 65 to 83, without any serious medical conditions including diabetes or Alzheimer's.

Research has been showing such a strong connection between the two conditions that some scientists are calling Alzheimer's "Type 3 diabetes," said Dr. H. Murray Todd, medical director of the Memory Disorder Center at Broward Health North in Deerfield Beach.

That means Type 2 diabetics, or those who are not dependent on insulin injections, could be much more likely to end up with Alzheimer's, Todd said.


"Two disorders that seem very dissimilar may, in the long scheme of things, turn out to be very similar in terms of what is going on in the brain," Todd said.

Type 2 diabetes is common among seniors, with 27 percent of U.S. residents older than 65 having the disease and another 13 percent being pre-diabetic, said Dr. Kenneth Burke, board director for the American Diabetes Association chapter in Fort Lauderdale. Yet many patients and their doctors probably aren't aware of the elevated Alzheimer's risk, Burke said.

While good diet, exercise and medication can allow most diabetics to live normal lives, "there is not much yet we can do about the advance of Alzheimer's," Burke said.

What makes the new TOMORROW clinical trial at Cleveland Clinic unique is that it will follow healthy seniors instead of those already diagnosed with Alzheimer's, said study co-investigator Dr. Po-Heng Tsai.

"Most of the [Alzheimer's] studies and treatments so far have focused on disease modification," he said. "There hasn't been much on prevention."

All candidates will undergo a genetic blood test to determine whether they have the TOMM40 and APOE genes. Research has shown APOE carriers are predisposed to Alzheimer's, and scientists suspect TOMM40 also may be a biomarker.

The double-blind trial will enroll seniors with and without the genes but will not disclose who tested positive to either participants or physicians. Some enrollees will be given the Type 2 diabetes medication Actos, others a placebo. All will be tracked up to five years.

The goal: to see whether, among genetically high-risk seniors, those who take Actos are less likely to develop Alzheimer's, or show symptoms later, than those on the placebo, Tsai said. The study also will examine if TOMM40 indeed is a predictor for Alzheimer's.

Actos came under the scrutiny of the Food and Drug Administration in 2010, following reports that the medication might be associated with bladder cancer in men. At the time, the FDA called for a 10-year study of the medication, to see if it posed a cancer risk, but did not withdraw Actos from the market.

Federal investigators also noted that the cancer reports involved patients who had the highest cumulative doses of Actos, with some having taken the drug for years.

Dr. Jeffrey Cummings, director of Cleveland Clinic's Lou Ruvo Center for Brain Health in Las Vegas, said TOMORROW study participants will take only a .8-milligram dose daily, much lower than the standard diabetic treatment, which will keep them at safe cumulative dose levels.

There currently are just a few FDA approved drugs for Alzheimer's, mostly cholinesterase inhibitors like Aricept, and they are prescribed after symptoms appear. Most work for only a short time or not at all, Tsai said, and do nothing to stop the disease's progress.

Scientists stumbled on off-label Alzheimer's treatment possibilities for pioglitazone, also called AD-4833 and the active ingredient in Actos, when previous clinical and animal studies suggested its anti-inflammatory properties might protect the brain.

Exactly why diabetes and Alzheimer's could be connected still isn't known, Broward Health North's Todd said. It may be partly because Type 2 diabetes affects the way the brain uses glucose (or blood sugar) and insulin, a hormone that helps blood sugar move into cells. Scans have shown Alzheimer's patients' brains also don't properly metabolize glucose.

The TOMORROW study, a phase III trial that will enroll about 5,800 people at 50 facilities worldwide, is financed through Actos partners Takeda Pharmaceuticals and Zinfandel Pharmaceuticals.

Multiple lawsuits have been filed against pharmaceutical manufacturers regarding Actos, alleging patients developed bladder cancer after using the drug. Last month, a jury in a Louisiana federal court ordered Takeda and Eli Lilly & Co. to pay a combined $9 billion in punitive damages, finding that the companies had hidden Actos' cancer risk, according to Bloomberg News.

The companies have said they will appeal the ruling, one of the largest levied in the United States against a drug manufacturer for improper handling of a product.

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Interested?

To participate in the TOMORROW study, call Cleveland Clinic in Weston at 954-659-6428