Cleveland Clinic is now enrolling patients in the first U.S. clinical trials designed to test two investigational drugs to treat LBD, which afflicts more than one million Americans. Researchers hope for results next year.
The studies, sponsored by drugmaker Axovant Sciences, involve about two dozen medical centers around the world.
Babak Tousi, M.D., head of the Clinical Trials Program at Cleveland Clinic Lou Ruvo Center for Brain Health is the principal investigator for the Cleveland site.
The six-month study will enroll about 240 patients nationally to test the safety and effectiveness of RVT-101, a tablet that researchers think can restore cognitive function, or thinking skills.
A second clinical trial will be led in Cleveland by James Leverenz, M.D, the director of the Cleveland Clinic Lou Ruvo Center for Brain Health and chair of the Scientific Advisory Council of the national Lewy Body Dementia Association.
The five-month study will investigate the safety and effectiveness of nelotanserin, a medication that researchers think can help people suffering from hallucinations and sleep disturbances.
Both trials are currently recruiting patients with the disease who are between the ages of 50 and 85. Interested participants should call the Lou Ruvo Center for Brain Health at 216-445-9009.
Dementia with Lewy Bodies is caused by the buildup of abnormal protein deposits, called “Lewy Bodies,” in brain cells. It was discovered in the early 1900s by scientist Frederick H. Lewy and can only be confirmed by a post-mortem brain autopsy.
According to Dr. Tousi, LBD may account for more than 15 percent of all cases of dementia. It’s often confused with Alzheimer’s and Parkinson’s diseases, which share causes and symptoms, so patients are often misdiagnosed.
People with Lewy Bodies in their brain often experience rapid decline in their balance, motor skills and memory.
They tend to be younger than people with Alzheimer’s and deteriorate more rapidly, often suffering anxiety attacks, hallucinations and nightmares. Many patients might have experienced acting out dreams for years prior to showing difficulty with thinking.
RVT-101 has been shown to raise levels of acetylcholine, a vital chemical in the brain that affects memory and behavior. Deficits in acetylcholine are a prominent feature of LBD.
Meanwhile, nelotanserin, a drug that has shown promise calming neuropsychiatric disturbances, will be tested for its ability to manage the visual hallucinations brought on by LBD.
For more information about the clinical trials, patients can click HERE
The following is from the drug manufacturer with more information about the Clinical Trials.
FAQ – Axovant Dementia with Lewy Body Clinical Program
What is Lewy Body Dementia?
Lewy body dementia, or LBD, is the second most common cause of neurodegenerative dementia affecting approximately 1.4 million individuals in the United States. It is an umbrella term for two related diagnoses – dementia with Lewy bodies, or DLB, and Parkinson’s disease dementia, or PDD.
Patients living with LBD may e xperience visual hallucinations, Parkinson’s like features, and fluctuations in cognition especially with attention and alertness. Given the varied clinical presentation, LBD is very hard to diagnose and may take more than a year for a doctor to diagnose LBD in a patient.
The distinction between PDD and DLB is somewhat arbitrary; both diseases are thought to be caused by the abnormal buildup of a protein called alpha-synuclein in clusters known as Lewy bodies in the brain. If dementia develops within one year of Parkinsonism, patients are diagnosed with DLB; if later, then they are diagnosed with PDD.
There are no approved therapies for the treatment of DLB in the United States or Europe, though donepezil, a drug that blocks the breakdown of acetylcholine, is approved for the treatment of DLB in Japan and the Philippines.
What drugs is Axovant developing for LBD?
Axovant is currently working on two investigational drugs for the treatment of Lewy body dementia or dementia with Lewy bodies: nelotanserin and intepirdine (RVT-101).
What is nelotanserin?
Nelotanserin is an oral, once-daily, investigational drug candidate currently being evaluated in patients with Lewy body dementia who are experiencing visual hallucinations. Nelotanserin is also being evaluated in patients with dementia with Lewy bodies who are experiencing REM Sleep Behavior disorder (RBD). RBD is a sleep disorder where patients affected physically act out their dreams in ways that may possibly lead to injury of the patient and/or bed partner.
How does nelotanserin work, and what potential benefits does it provide?
Nelotanserin is a potent and highly selective inverse agonist of the 5HT2A receptor. Nelotanserin is thought to work by reducing the activity of the 5HT2A receptor which is implicated in visual hallucinations and other neuropsychiatric disturbances experienced by patients living with Lewy body dementia.
What is the clinical status of nelotanserin?
Originally developed for primary insomnia, nelotanserin has been tested in nearly 800 individuals and appears to be well-tolerated in those studies. A phase 2 clinical trial with nelotanserin demonstrated that nelotanserin improved sleep consolidation and reduced the number of transitions between sleep stages – which may be triggers for RBD.
Nelotanserin is being studied as a once-daily oral pill, administered with or without food.
Nelotanserin is being studied as a potential treatment for the behavioral aspects of the disease, particularly visual hallucinations and REM sleep behavior disorder (RBD). According to the Lewy Body Dementia Association, up to 85% of patients with DLB experience visual hallucinations and up to 80% of patients with DLB experience RBD.
What is intepirdine (RVT-101)?
Intepirdine (RVT-101) is an oral, once-daily investigational drug candidate currently being evaluated in patients with dementia with Lewy bodies (called the HEADWAY-DLB trial) and mild-to-moderate Alzheimer’s disease (called the MINDSET trial).
How does intepirdine (RVT-101) work, and what potential benefits does it provide?
Intepirdine is a potent and selective 5-HT6 receptor antagonist and is thought to work by promoting the release of acetylcholine within the brain. Acetylcholine is a vital chemical necessary for cognition and function. Patients with DLB and AD have deficits in acetylcholine levels in the brain.
What is the clinical status of intepirdine (RVT-101)?
Intepirdine has already been tested in 15 clinical studies, including a 684-subject study in patients with mild to moderate Alzheimer’s disease where the combination of intepirdine and donepezil was observed to provide statistically significant benefits on measurements of cognition and the ability to perform daily living activities, as compared to donepezil alone.
Cholinergic deficits may be even greater in LBD than AD, and cholinesterase inhibitors have shown benefits in Parkinson’s disease dementia and dementia with Lewy bodies. Hence, there is a strong scientific rationale that by boosting acetylcholine levels with intepirdine may positively impact LBD.
Across all 15 clinical studies completed more than 1,300 individuals have received intepirdine, and we have seen a low rate of adverse events in these studies.
Intepirdine is being studied as a once-daily oral pill, administered with or without food.
Intepirdine is being studied as a potential treatment for the cognitive and functional problems seen in mild to moderate Alzheimer’s patients. The ongoing study of intepirdine in DLB patients (HEADWAY) could be the first pivotal study ever conducted in the United States for patients with DLB.
HEADWAY-DLB is a 6-month double-blind study evaluating the safety and effectiveness of intepirdine (RVT-101) for treating dementia with Lewy bodies. Approximately 240 people are expected to participate in the study. For more information, please visit lewybodystudy.com
What does it mean to be an “investigational medication?”
An investigational medication is a drug that is not yet approved by a regulatory authority such as the FDA but is available to patients who participate in clinical research programs that evaluate the safety and efficacy of these drugs. The process of evaluating investigational medications is tightly structured and regulated to protect patient wellbeing. Before being administered in any humans, these investigational medications undergo extensive testing in laboratories and animals. They then enter small phase 1 clinical studies, before being tested in progressively larger studies to establish their safety and efficacy.