New Results From Four Alzheimer's and Dementia Clinical Trials Highlight "Developing Topics" Reports at AAIC 2012

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Jul 18, 2012, 11:30 ET

- Phase 2b study of a new symptomatic drug -

- One-year extension trial of a medical food -

- 9-month trial of a dietary supplement -

- 18-month study of a home-based care coordination intervention -

VANCOUVER, British Columbia, July 18, 2012 /PRNewswire-USNewswire/ -- Results from four clinical trials reported at the Alzheimer's Association International Conference® 2012 (AAIC® 2012) demonstrate the wide variety of approaches being pursued to improve memory, thinking, quality of life, and quality of care for the millions of people with Alzheimer's, their caregivers and family members.

The four studies were presented as "developing topics" at AAIC 2012, which often include last minute calculations and data analyses. They include:

Six-month, Phase 2b trial results on EVP-6124 (EnVivo Pharmaceuticals), a selective, partial, alpha-7 nicotinic agonist. In people with mild to moderate Alzheimer's, the experimental drug showed statistically significant benefits on several cognitive scales. This is a symptomatic drug with a different mechanism of action than the current FDA-/EMA-approved Alzheimer's drugs.
48-week results of a randomized controlled study plus open label extension in people with mild Alzheimer's of a medical food, Souvenaid (Nutricia/Danone), showed positive results on memory performance sustained for one year. According to the manufacturers, Souvenaid includes a specific nutrient combination designed to support synapse formation and function in Alzheimer's.
IDEALE study is a multi-center study in Italy to assess the effectiveness and safety of oral citicoline in people with mild vascular cognitive impairment. Citicoline is a dietary supplement that may increase the availability of certain neurotransmitters. At nine months, a significant difference was found on the MMSE, a test of memory and cognition, between citicoline users and non-users.
An 18-month study by Johns Hopkins University researchers tested the efficacy of a home-based, care coordination intervention in more than 300 community residing people with memory disorders. Results suggest that the intervention improved care quality, quality of life, and ability to remain in home.

"Ridding the world of Alzheimer's disease and other dementias is a global challenge of the utmost importance," said William Thies, PhD, Alzheimer's Association® Chief Medical and Scientific Officer. "The urgency is clear. With the aging population and the growing prevalence of Alzheimer's, caring for people with dementia will cost more than $1 trillion annually by 2050 in the U.S. alone, creating an enormous strain on the already stressed healthcare system, families, and government budgets."

"As a result, having a diversity of approaches and treatment options in the pipeline is important to drug development and to affected families. While researchers are searching for ways to alter the course and prevent Alzheimer's, we still need better treatments and care options for people who have the disease now," Thies said.

Phase 2b Results of a New Symptomatic Drug

EVP-6124 (EnVivo Pharmaceuticals) is a selective, partial, alpha-7 nicotinic agonist that, in previous testing, has demonstrated cognitive benefits in normal volunteers and in preliminary study participants with schizophrenia or Alzheimer's.

Alpha-7 nicotinic agonists amplify the effects of acetylcholine, a brain chemical that is essential for normal brain and memory function. Acetylcholine is greatly reduced in people with Alzheimer's. While other approved drugs also have this effect, alpha-7 nicotinic agonists achieve the result by a different mechanism of action.

Dana Hilt, MD, Senior Vice President of Clinical Development and Chief Medical Officer of EnVivo and colleagues at the company conducted a 6-month, double blind, placebo-controlled, Phase 2b study of three doses of EVP-6124 in 409 people with mild to moderate Alzheimer's who were either on stable Alzheimer's therapy (donepezil or rivastigmine) or on no therapy. [Placebo (n=104), 0.3 mg/d (n=104), 1 mg/d (n=101), 2 mg/d (n=100).]

Primary efficacy endpoints were two established and accepted scales for measuring memory, language, attention and other cognitive abilities (ADAS-Cog-13 and the CDR-SB). Additional pre-specified endpoints included several measures of cognition, language, mood, and ability to function independently (ADAS-Cog-11, COWAT, CFT, NPI, ADCS-ADL (23)), plus composite measures for cognition, memory, and executive function.

After 23 weeks of treatment, the researchers found that, compared to the placebo group, the 2 mg treatment group had statistically significant benefits on the ADAS-Cog-13 and CDR-SB. They also saw a significant effect on the ADAS-Cog 11, COWAT, cognition composite, memory composite, and executive function composite. They reported that EVP-6124 was safe and well tolerated with some mild to moderate gastrointestinal side effects in a minority of patients in both the 1 and 2 mg dose groups.

"In our study, EVP-6124 provided significant benefits for people with mild to moderate Alzheimer's whether they were on currently-approved therapy or not," Hilt said. "While the currently approved Alzheimer's drugs provide modest improvement in cognition and function, additional symptomatic therapies are desirable. We believe that, with further testing, EVP-6124 potentially could be used as a monotherapy or added on to other approved Alzheimer's drugs. These results support studying the drug in further Phase 3 studies."

One-year Results in Mild Alzheimer's Disease with a Medical Food Product

Souvenaid® (Nutricia/Danone) is a medical food* product that, according to the manufacturers, contains a specific nutrient combination designed to support the formation and function of brain connections known as synapses.

Synapses are where brain cells pass chemical signals to other cells, and are essential to proper brain function. Alzheimer's disease destroys synapses and disrupts both the way electrical charges travel within cells and the activity of brain chemicals known as neurotransmitters.

In the 24-week, double-blind, randomized, controlled study known as Souvenir II, 259 people with mild Alzheimer's who were not taking any Alzheimer's drugs were randomized to receive either Souvenaid 125 ml once daily or a control drink. A 24-week open label extension (OLE) study, reported at AAIC 2012, enrolled patients who completed Souvenir II. In the OLE study, which was conducted at 26 study centers in six European countries (the Netherlands, Germany, France, Belgium, Italy and Spain), all patients received Souvenaid 125 ml once daily. The primary objective was to investigate long term safety and compliance following the initial double blind study. Compliance was assessed using a daily diary and by studying (nutritional) biomarkers of compliance. The memory domain score from the Neuropsychological Test Battery (NTB), the primary endpoint of the initial study, was included as an exploratory outcome in the OLE study.

The Souvenir II study recently reported a statistically significant beneficial effect on memory (Scheltens, et al. J Alz Dis, 2012). Of the 238 patients who completed that study, 198 patients entered the OLE study; 183 completed it. The OLE study results showed that 48-week use of Souvenaid was safe and well-tolerated, with high compliance (>90%). Additionally, it indicated that:

Memory performance continued to improve significantly in study participants with mild Alzheimer's who received Souvenaid for the full 48 weeks.
In the group that received placebo for the first 24 weeks, there was a significant improvement in memory scores during the OLE.

About 25% of study participants started taking approved Alzheimer drugs during the OLE; the scientists found memory improvement to be consistent across both groups.

"Souvenir II is the second positive trial showing the potential of this nutritional intervention in the early stages of Alzheimer's, and the open label data further extends our understanding. An EU-funded trial of the concept is underway, targeting patients with prodromal Alzheimer's. We look forward with great interest to the outcome," said Philip Scheltens, MD, PhD, Professor of Cognitive Neurology and Director of the Alzheimer Center at the VU University Medical Center in Amsterdam, and principal investigator of the trial.

* A medical food is defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) as "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."

Citicoline Supplement Tested in Older Adults with Mild Vascular Cognitive Impairment

The IDEALE study, led by Pietro Gareri, MD, PhD, of the Ambulatory Center for Dementia, Catanzaro, Italy, is a multicenter study in six regions of Italy to assess the effectiveness and safety of citicoline in 265 people aged 65+ with mild vascular cognitive impairment.

Citicoline is a dietary supplement available in more than 70 countries. Citicoline may increase the availability of certain neurotransmitters, including acetylcholine (an important brain neurotransmitter for memory processes), norepinephrine, and dopamine; and neuronal membrane phospholipids, chiefly phosphatidylcholine, which are major constituents of cell membranes.

Participants in IDEALE included older adults with MMSE (Mini Mental State Examination) scores less than or equal to 21 or people with subjective memory complaints, no evidence of deficits on MMSE and evidence of vascular lesions on brain scans. People with probable Alzheimer's disease were excluded. The study group received 500 mg of oral citicoline twice a day. Participants underwent brain imaging scans, and testing for thyroid function, cognition/memory (MMSE), independent functioning (ADL, IADL), and mood at the beginning of the study, after three months, and after nine months.

The researchers found that, after nine months, the people taking citicoline showed a slight but not significant benefit in MMSE score (22.4 at baseline, 22.9 after nine months). Those who were not taking citicoline declined (21.5 at baseline, 19.6 at nine months). The difference between the two groups was statistically significant. No adverse events were recorded.

"This study showed that citicoline is effective and well tolerated in mild vascular cognitive impairment," Gareri said "When cognitive testing scores over nine months remain unchanged in people developing cognitive impairment, we think this may be considered a good outcome."

Care Coordination Program Improves Quality of Care and Quality of Life of People with Dementia

Previous research shows that people with Alzheimer's and other dementia disorders are at increased risk for disability, medical and mental health conditions, and placement in assisted living or nursing home settings. Similarly, their caregivers are also at increased risk for a host of medical, mental health, social and economic difficulties.

Evidence also suggests that education about and management of the disease, focused on identifying and treating symptoms and providing practical and emotional support, can provide multiple benefits for those with Alzheimer's and their loved ones by minimizing the risk of complications and improving quality of life, mood, overall health, and prolonging independence.

Quincy Miles Samus, PhD, and colleagues at the Johns Hopkins University School of Medicine tested the efficacy of a multidimensional care coordination model to improve quality of care and other outcomes for community residing people with memory disorders, known as The Maximizing Independence at Home (MIND at Home) trial.

The 18-month controlled trial included 303 people with cognitive disorders (265 with dementia; 38 with mild cognitive impairment) age 70+, living at home in 28 zip codes near Baltimore, MD. Participants were randomized to receive the care coordination intervention (n=110) or augmented usual care (n=193). The intervention team included paraprofessionals specially trained in evidence-based dementia care, a psychiatric nurse, and a geriatric psychiatrist. The team implemented a standardized care coordination protocol consisting of a multidimensional needs assessment, community resource referrals, memory disorder education, counseling, and problem-solving, which were supported by a customized web-based application to monitor care progress.

Primary outcomes included unmet needs and time to transfer out of the home. Secondary outcomes were participant quality of life, neuropsychiatric symptoms, and depression.

The researchers found that study participants had a wide range of unmet needs. Home and personal safety issues, general medical care, meaningful activities, and legal issues were the most common. The intervention group had a greater decrease in total unmet needs from the beginning of the study to 18 months compared to the control group, with the most significant reductions in safety and legal issues. In addition, intervention participants were less likely to permanently leave their home or die compared to controls (30.0% vs. 45.6%) and had a significant reduction in time to leaving the home for any reason. Self-reported quality of life was better in the intervention group at 18 months. No group differences were found on proxy-rated quality of life, neuropsychiatric symptoms, or depression.

"Our study provides promising preliminary evidence that the intervention can promote the ability to age in place and improve care quality," Samus said. "We are hopeful this study will help guide how community-based dementia care can be effectively and efficiently delivered in the future."

"Further work is needed to evaluate how beneficial this intervention would be in other communities, such as those who live in disadvantaged areas. Plus, we need to work out how it might be paid for, sustained, and made available to larger groups of people over the long term," Samus said.

Recently, the Alzheimer's Association launched a new online assessment program, Alzheimer's Navigator™ (www.alzheimersnavigator.org), to help caregivers and people with dementia evaluate their needs, identify action steps and connect with local programs and services. Developed with feedback from people living with Alzheimer's and caregivers, Alzheimer's Navigator allows users to reassess needs and adjust care plans as the disease progresses. Users can create and manage care teams so that multiple people, including long-distance caregivers, can access and participate in the customized action plan.

Alzheimer's Association chapters nationwide facilitate more than 4,500 support groups and conduct 20,000 education programs annually. The Association provides consultation to 250,000 people in need each year through its toll-free 24/7 Helpline (1-800-272-3900). The only one of its kind, the Helpline is staffed by masters-level counselors and provides information and guidance in more than 170 languages and dialects.

About AAIC

The Alzheimer's Association International Conference (AAIC) is the world's largest conference of its kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

About the Alzheimer's Association

The Alzheimer's Association is the world's leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. For more information, visit www.alz.org or call 800-272-3900.

SOURCE Alzheimer's Association