The results of a recently completed pilot study have cleared the way for more large-scale clinical trials to determine the efficacy and safety of using pioglitazone (Actos) to treat Alzheimer’s disease.
A drug that reduces the amount of glucose in the blood, pioglitazone is commonly used for the treatment of type II diabetes.
Led by David S. Geldmacher, M.D., of the University of Virginia Health System in Charlottesville, the pilot was a double-blind, placebo-controlled trial conducted at two academic medical center outpatient clinics. The randomized controlled trial lasted 18 months.
According to the research team, the drug was well tolerated by patients. Peripheral edema was the only issue of note and was found to occur in four out of fourteen patients.
The online report, published in the Archives of Neurology, suggested that the risks for peripheral edema, heart failure and other cardiovascular issues be closely monitored with clinical trials involving thiazolidinedione agents for Alzheimer’s disease going forward.
While the drug was well tolerated, the study did not reveal the drug’s effectiveness in slowing the progression of Alzheimer’s. The Alzheimer’s Disease Assessment Scale (ADAS) measured only a slight difference in cognition with an average change of only 0.746 points each month.
“The small and nonsignificant differences suggest that mild to moderate Alzheimer’s disease is not likely to be an appropriate population for further study of thiazolidinediones,” the researchers wrote.
The report went on to suggest that the small study was not appropriately powered to make a fully-researched determination about efficacy. The primary outcome measure centered on the presence of adverse effects in patients, and functions such as cognition, activities of daily living and neuropsychiatric symptoms were secondary measures.
The trial included 29 elderly, non-diabetic patients presenting with Alzheimer’s disease who were provided either 45 mg of pioglitazone daily or a placebo that was accompanied by 200 IU of vitamin E daily.
Patients continued use of cholinesterase inhibitors, a commonly prescribed drug used to prevent breakdown of acetylcholine in Alzheimer’s patients. Acetylcholine is a chemical messenger important for learning and memory.
Patients were also allowed to initiate memantine (Namenda) therapy during the trial, another widely prescribed intervention for Alzheimer’s disease.
Based on the results, researchers suggested that future studies be conducted at earlier stages of Alzheimer’s progression and focus down on the effects that pioglitazone may have toward positively impacting inflammation caused by microglial activation. The report suggested the use of nuclear imaging techniques as an effective tool or biomarker for this type of research.
Because thiazolidinediones—including pioglitazone and rosiglitazone (Avandia)—have the ability to suppress microglial inflammation, it was suggested that further study was warranted.
Previous studies had suggested promise with rosiglitazone, but when that particular drug was cleared for larger clinical trials, it failed.
Researchers promoted further study of thiazolidinediones but also cautioned that the drugs may simply not have enough of an effect on microglial activation to be clinically relevant going forward.
More than 5 million people in the U.S. alone currently have Alzheimer’s disease, and this number is expected to jump to 13.5 million by 2050.
Source: Archives of Neurology