Alzheimer's, Dementia & Mental Health
Clinical Trial Stops the Cognitive Decline for
Alzheimer’s Patients, Slows Brain Shrinkage
Phase II study is first to show combined benefits
of IGIV on clinical outcomes
April 13, 2010 – A Phase II clinical trial using
naturally occurring antibodies in human blood has stopped the decline in
the thinking abilities of mild-to moderate-stage Alzheimer’s patents
over 18 months. It also significantly reduced the rate of shrinkage of
their brains, which is common in AD patients.
These and other findings from the Phase II clinical
trial of GAMMAGARD LIQUID and GAMMAGARD S/D Immune Globulin Intravenous
(Human) (IGIV) for Alzheimer's disease (AD) at the New York-Presbyterian
Hospital/Weill Cornell Medical Center were presented today at the
American Academy of Neurology (AAN) meeting in Toronto.
|
|
Related Stories |
|
|
|
Worsening Memory May Be Too Quickly Dismissed:
Could Lead to Alzheimer's
 ‘Concept of mild cognitive impairment as a
predementia manifestation of Alzheimer's disease is substantiated’
April 5, 2010
Self-Administered Test to Screen for Early Dementia,
Alzheimer's Available Online
 Ohio State Neurologist says it takes less than 15
minutes to complete, is a reliable tool for evaluating cognitive
abilities
March 31, 2010
Research Leader Says Discovery Offers Hope Early
Alzheimer’s Disease Can Be Cured
 Team uncovers new explanation for the spread of key
protein, Tau, within the brain
March 1, 2010
Remember Magnesium If You Want to Remember at Any
Age
Study finds new synthetic supplement improves memory
and staves off age-related memory loss
Feb. 22, 2010
Hypertension Predicts Dementia in Seniors Losing
Ability to Organize, Make Decisions
 Control of high blood pressure in this senior
citizen group could cut in half the projected 50% five-year rate of
progression to dementia’
Feb. 8, 2010
Drowsiness, Staring, Other Mental Lapses by Senior
Citizens May Signal Alzheimer's Disease
Seniors with mental lapses were 4.6 times more
likely to have dementia than those without mental lapses
Jan. 18, 2010
Seniors with Subjective Memory Loss (where did I put
keys?) at Increased Risk of Dementia
Significant percentage of people with early
subjective symptoms may experience further cognitive decline; few
without these symptoms decline
Jan. 12, 2010
Read the latest news on
Alzheimer's, Dementia & Mental Health |
|
In a Late-Breaking News presentation at the AAN on
Wednesday, April 14, at 7:30 am, Dr. Norman Relkin, director of the
Memory Disorders Program at New York-Presbyterian/Weill Cornell, will
report that patients receiving IGIV once or twice a month for 18 months
had significantly lower rates of ventricular enlargement (6.7% vs 12.7%
per year) and less whole-brain atrophy (1.6% vs 2.2% per year) than
control subjects who initially received placebo.
Dr. Relkin's findings were based on two independent
analyses of brain-imaging data from 20 patients who underwent serial MRI
scans during the Phase II study of IGIV for AD.
"Past AD studies that used MRI measures found no
change or an accelerated rate of brain shrinkage after investigational
treatments," Dr. Relkin notes.
"To the best of my knowledge, this is the first
trial in which long-term clinical benefits in Alzheimer's patients were
accompanied by objective signs of reduced brain degeneration."
Dr. Relkin is also an associate professor of
clinical neurology and neuroscience at Weill Cornell Medical College in
New York City. He was the principal investigator in the Phase II study
and is currently leading a multicenter Phase III study of IGIV for
Alzheimer's.
A typical AD patient's brain shrinks three to four
times faster than a healthy older adult's as a consequence of
accelerated brain cell death. This shrinkage of brain tissue causes the
fluid-filled ventricles at the center of the brain to enlarge at a
faster than normal rate. Changes in the size of the brain and ventricles
can be measured accurately by analyzing results from two or more MRI
scans obtained at an interval of at least several months apart.
The unprecedented reductions in these measures
after IGIV reported by Dr. Relkin and his colleagues could indicate that
IGIV exerts a disease-modifying effect that the current generation of
approved AD treatments lack.
Dr. Relkin also found that rates of brain shrinkage
after IGIV intervention were independent of the subject's age, gender
and brain volume at the start of the study but strongly correlated with
dose of IGIV and the clinical outcomes after 18 months of intervention.
The Weill Cornell research team also found that AD
patients who responded best to IGIV did not measurably decline over 18
months, and had an average rate of brain shrinkage and average rate of
ventricular enlargement comparable to the rate previously reported in
normal elderly individuals.
"A dose-related effect of an Alzheimer's
intervention on brain ventricular enlargement has never been seen
before, and it suggests that IGIV may, indeed, be sparing brain tissue,"
says Dr. James Brewer, a neurologist and assistant professor of
neurology at the University of California at San Diego.
Dr. Brewer independently analyzed the MRIs from the
Phase II IGIV study, and his findings closely matched those obtained by
Dr. Dana Moore, a postdoctoral fellow working with Dr. Relkin at Weill
Cornell.
"I am particularly looking forward to examining the
Phase III data when that study is completed," Dr. Brewer states. "Since
it involves a considerably larger group of patients, it will permit us
to obtain more detailed measures of atrophy in the brain regions
specifically vulnerable to Alzheimer's disease."
More details about the study's cognitive testing
results will be reported in a later presentation at the AAN meeting by
Dr. Diamanto Tsakanikas, who performed cognitive and other testing of
the study's participants. Dr. Tsakanikas is a clinical assistant
attending neuropsychologist at New York-Presbyterian Hospital/Weill
Cornell Medical Center and an instructor of neuropsychology in the
Department of Neurology and Neuroscience at Weill Cornell Medical
College.
While conducting the testing, Dr. Tsakanikas was
blinded to whether patients were receiving IGIV or placebo and to the
IGIV dose.
When the unblinded study results were later
analyzed, her testing indicated that AD patients who received
uninterrupted IGIV for 18 months showed significantly less decline in
their overall function and thinking abilities than AD patients initially
given an inactive placebo.
In some cases, IGIV intervention resulted in
improvements in certain areas of cognitive functioning. "Functions
mediated by the frontal regions of the brain showed the most consistent
benefits in IGIV responders," says Dr. Tsakanikas.
The Phase II study involved 24 patients with mild
to moderate Alzheimer's disease who were randomly assigned to receive
IGIV (16 patients) or saline placebo (eight patients) for six months.
Over the following 12 months, the initially
placebo-treated group were subsequently received various doses of IGIV
while the other 16 patients had uninterrupted IGIV at the initially
assigned dose. The study included a comparison of four dosing regimens
of IGIV, with doses ranging from 0.2 g/kg every two weeks to 0.8 g/kg
every four weeks.
"The Phase II study was carried out with the
explicit goal of determining whether further testing of IGIV for
Alzheimer's was justified," Dr. Relkin points out.
"It succeeded in achieving that goal with a
relatively small number of subjects. However, we now have to await the
results of the larger, pivotal Phase III study to establish the
magnitude of its effects on rate of brain atrophy and to confirm whether
IGIV is safe and effective for treating AD."
IGIV is being tested as a potential agent for AD
immunotherapy because it contains antibodies against beta-amyloid (A?),
which is the main constituent of amyloid plaques in the brains of AD
patients.
IGIV is not approved to treat Alzheimer's disease
but it is approved in the United States and other countries for certain
immune deficiency and autoimmune disorders. A critical Phase III study
of IGIV for AD, supported jointly by the National Institutes of Health (NIH)
and Baxter Healthcare, is currently enrolling patients at 35 sites in
North America (see more below).
The Phase II study was supported by Baxter
Healthcare, the Citigroup Foundation and The Clinical Translational
Science Center (CTSC) of Weill Cornell Medical College.
Enrollment in Phase III Trial
The trial includes 35 actively enrolling sites at
leading academic centers in the United States that are members of The
Alzheimer's Disease Cooperative Study (ADCS), with an additional 12
sites pending in the U.S. and Canada. The involvement of the ADCS and
NIH in the conduct of the Phase III trial will ensure the highest level
of independent scientific evaluation of the potential role of IGIV in
the treatment of Alzheimer's patients. For more information about
enrolling in the ongoing Phase III trial, please visit
www.GAPSTUDY.com or contact Jeffree Itrich at the Alzheimer's
Disease Cooperative Study at (858) 622-5827 or
jitrich@ucsd.edu.
New York-Presbyterian Hospital/Weill Cornell
Medical Center
New York-Presbyterian Hospital/Weill Cornell
Medical Center, located in New York City, is one of the leading academic
medical centers in the world, comprising the teaching hospital New
York-Presbyterian and Weill Cornell Medical College, the medical school
of Cornell University.
www.med.cornell.edu.
