Aggressive efforts to develop therapies for Alzheimer’s disease continue around the world in hopes of understanding, slowing, and even stopping the ravages of the ailment. Now, you may be able to help in research efforts to bring new treatments that improve quality of life for those who suffer from Alzheimer’s and other dementia-related diseases by joining a study that looks at excess cortisol in the brain.

In collaboration with drugmaker Actinogen, Charter Research is seeking volunteers in a new clinical trial of Xanamem, an oral medication designed to treat individuals with mild or moderate dementia due to Alzheimer’s. Xanamem was developed in response to evidence of a strong association between chronically-raised cortisol levels and the development of cognitive impairment in Alzheimer’s disease. The drug is designed to target and block production of cortisol inside brain neurons.

About Xanamem and the clinical trial

As you may know, Alzheimer’s is characterized by progressive cognitive decline and significant interference in daily function. The first observable declines in daily functioning may typically involve cognitively complex activities such as performing household duties, grocery shopping, or paying bills.

While no single clear cause has been identified for the development of Alzheimer’s disease, there is strong evidence to support an association between excess cortisol and the development and progression of Alzheimer’s disease. The Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL), published in 2017, provides some of the most powerful evidence supporting the cortisol hypothesis. The study demonstrated that healthy, elderly individuals with higher cortisol levels were significantly more likely to develop Alzheimer’s disease than those with lower cortisol levels. The study authors concluded that therapies aimed at lowering cortisol levels should be considered as a potential way of addressing the development of Alzheimer’s disease.

Cortisol, informally known as the “stress hormone,” is produced in times of stressful physical and mental  events. While this response is normal, prolonged elevated cortisol levels can become toxic to the neurons (nerve cells) in the brain. Individuals with higher cortisol include those with diabetes, depression, schizophrenia, bipolar disorder, and post-traumatic stress disorder (PTSD).

Blood cortisol levels are known to rise naturally with normal aging. What’s more, increasing age is the single biggest risk factor for developing Alzheimer’s disease, and more than half of cognitively normal 65-year-olds have been shown to have persistently raised cortisol.

Xanamem’s novel approach inhibits an enzyme that converts inactive cortisone into active cortisol. The enzyme is present at high levels in the hippocampus and frontal cortex, areas of the brain associated with cognitive impairment in neurological diseases, including Alzheimer’s disease.

A promising start

Dr. Edgardo Rivera, Charter Research Medical Director in Orlando, said earlier trials suggest Xanamem has promise in reducing the progression of cognitive decline. Indeed, Actinogen’s Phase 1 Xanamem trial showed rapid improvements in cognition for attention tests and good tolerability in healthy older volunteers who received daily doses of 5 mg or 10 mg. This supports the results from another Phase 1 trial in healthy older volunteers treated with 20mg doses.

Xanamem is different from currently available Alzheimer treatments, many of which are based on monoclonal antibodies. Those drugs, the first FDA-approved therapies for Alzheimer’s shown to slow the rate of cognitive decline by reducing amyloid protein deposits, which along with tau proteins have been linked to Alzheimer’s.

Rivera noted that in early trials Xanamem has a better safety profile than the monoclonal antibodies drugs. Side effects of currently available treatments can include chills, fever, nausea, joint pain and increased risk of intercranial bleeding or hemorrhagic stroke.

“I’m not saying that they are dangerous, but they do have some side effects that can be serious,” he said. “This other medicine has not had those types of problems yet.”

Why volunteer?

While finding an effective treatment for Alzheimer’s is the hope of all who suffer from the disease, the primary goal of clinical trials is to advance medicine, Rivera said.

“Our main goal should be to advance medicine and help find a cure or treatment for these diseases for our fellow citizens, for your family members that are coming behind you,” he said. “Because people like you did this in the past for other treatments like blood pressure medications, insulin, and even aspirin, that’s where the hope should be. That this particular medicine is going to prove to be good and therefore help treat the rest of society.”

Some trial participants who place a lot of hope on their personal condition are disappointed if they don’t see any improvement, Rivera said. But anyone considering volunteering should understand that improved personal health, while very important, is a secondary benefit of any clinical trial.

“I had a patient who was very upfront and blunt,” Rivera recalled. “He said, ‘I am 70, and I don’t know if I’ll last another two years, five years, 10 years. But what I do know is that my kids and my grandkids are now starting to live. So, I’m doing this for them. Not so much for me. My timecard is almost punched.’”

What to expect when you apply

Candidates for the trial will first go through prescreening that includes reviewing medical and medication histories and performing baseline memory testing. That information will be used to match candidates to the best possible study for them.

If the Xanamem trial is best for them based on the prescreening, additional trial-specific screening will be done. This process may take up to 10 weeks. Candidates who meet all the inclusion criteria and have no exclusion criteria will be enrolled in the study.

The clinical trial will include approximately 220 participants from around the world. Participants will be randomly assigned into either the drug or placebo group and will help assess the safety, tolerability, and efficacy of Xanamem.

How long will the trial last?

Successful candidates will take part in the trial for up to approximately 11 ½  months. The trial consists of a pre-screening period of up to six weeks, an additional screening period of up to four weeks, a treatment period of nine months, and a four-week follow-up period.

To learn more about this new potential medication, call Charter Research at 407-337-3000 (Orlando) or 352-441-2000 (The Villages). You can also fill out the form on the Alzheimer’s Cortisol Study page, and one of our representatives will call you within 24 hours (excluding weekends).