CLINICAL TRIALS
The following is a list of research studies currently being conducted in the Yale Alzheimer’s Disease Research Unit. Those studies that are actively seeking participants are listed first:
TREATMENT STUDIES
Enrolling
Bapineuzumab for mild to moderate AD. Bapineuzumab (formerly known as AAB-001) is a humanized monoclonal antibody that is administered by intravenous infusion and is directed against the ß-amyloid protein. This is an 18-month, placebo-controlled, Phase 3 study of the efficacy and safety of Bapineuzumab (with a total of approximately 20 visits). Permits concurrent treatment with cholinesterase inhibitors and memantine. Subjects will be required to have five brain MRIs provided with study participation. (MMSE 16-26) HIC#0801003387 and HIC#0801003388
LY450139 for mild to moderate AD. LY450139 has a novel mechanism of action as a functional inhibitor of gamma-secretase with the ability to inhibit the synthesis of ß-amyloid, potentially slowing the underlying rate of Alzheimer’s disease progression. This is a 20-month, placebo-controlled, Phase 3 study of the efficacy and safety of LY450139 (100 mg, 140 mg, or placebo once daily; 66.7% of subjects will receive active medication) involving a total of 20 visits. Permits concurrent treatment with cholinesterase inhibitors and memantine. (MMSE 16-26) HIC#0803003585
Dimebon for mild to moderate AD. Dimebon is an oral small molecule with multiple pharmacological effects. Although the mechanism of Dimebon is unclear, the most potent effect established to date is the inhibition of mitochondrial depolarization which may result in improved neuronal function and survival in Alzheimer’s disease. Results from a 6-month trial of Dimebon conducted in Russia in patients with Alzheimer’s disease demonstrated statistically significant improvement in cognition, activities of daily living, and global function. The present trial is a 6-month, placebo-controlled, Phase 3 study of the efficacy and safety of Dimebon (5 mg, 20 mg, or placebo three times daily; 66.7% of subjects will receive active medication) involving a total of 8 visits. Does not permit concurrent treatment with cholinesterase inhibitors or memantine. (MMSE 10-24) HIC#0805003830
ELND005 for mild to moderate AD. ELND005 (formerly known as AZD-103) is a compound that has been shown to inhibit ß-amyloid aggregation and reduce ß-amyloid plaque load while improving cognitive deficits in transgenic mice. (ß-amyloid plaques are thought to be chiefly responsible for the neurodegeneration associated with AD.) This is a 19-month, placebo-controlled, Phase 2 study of the efficacy and safety of ELND005 (250, 1000, or 2000 mg twice daily; 75% of subjects will receive active medication) involving a total of 16 visits. Permits concurrent treatment with cholinesterase inhibitors and memantine. (MMSE 16-26) HIC#0712003331
PF-04494700 for mild to moderate AD. PF-04494700 (formerly TTP488) is an antagonist of the Receptor for Advanced Glycation Endproducts (RAGE) that is being developed as a potential treatment for AD. RAGE is known to be involved in the transport of ß-amyloid from peripheral to central compartments, so antagonism of the receptor may modulate ß-amyloid transport resulting in changes in both plasma and cerebrospinal fluid (CSF) levels. This is a 20-month, placebo-controlled, Phase 2 study of the efficacy and safety of PF-04494700 (5 mg and 20 mg daily; 66.7% of subjects will receive active medication) involving a total of 8 visits. Permits concurrent treatment with cholinesterase inhibitors and memantine. (MMSE 14-26) HIC#0801003458
ACC-001 for mild to moderate AD. ACC-001 is an active immunization against the ß-amyloid protein that is administered by intramuscular injection to stimulate clearance of amyloid plaques. This is a 27-month, placebo-controlled, Phase 2a multiple-ascending dose study of ACC-001 with and without QS-21 adjuvant (involving approximately 25 visits). Permits concurrent treatment with cholinesterase inhibitors and memantine. Subjects will be required to have five brain MRIs provided with study participation. (MMSE 16-26) HIC#0709003057
ABT-089 for mild to moderate AD. Nicotinic agonists offer the potential benefit of direct and selective activation of neuronal nicotinic receptors (NNRs) even where acetylcholine levels are diminished by AD. Preclinical data suggest that selective activation of NNRs may produce symptomatic improvement in AD and limit the side effects observed with the cholinesterase inhibitors. ABT-089 is a NNR partial agonist that has demonstrated efficacy in animal models of attention, learning, and memory.
This is a 12-week, placebo-controlled, Phase 2 dose-ranging study of the efficacy and safety of ABT-089 (involving a total of 8 visits). Subjects must be receiving stable doses of cholinesterase inhibitors for at least 90 days prior to study drug administration. (MMSE 12-26) HIC# 0711003285
Home-Based Assessment for healthy elderly subjects. This is not a drug trial, but a study designed to help us determine the best home-based assessment method for future AD prevention trials in elderly subjects at risk for memory problems and AD. Currently, prevention trials require large numbers of subjects to receive several time-consuming clinic evaluations. This is a 4-year study in which healthy subjects (age 75 or older) are randomized into one of three different at-home methods of test administration and data collection (mail-in survey, automated telephone survey, and computer-based assessment). As part of the study, all participants will be given a multi-vitamin to be taken twice daily. (MMSE≥26) HIC#709003080
Closed To Enrollment
DHA for mild to moderate AD. Abundant evidence supports the choice of docosahexaenoic acid (DHA), an omega-3 fatty acid, as a treatment to slow the rate of cognitive decline AD. Epidemiologic studies show a reduced risk of AD associated with DHA consumption, and studies in mouse models of AD show that dietary DHA reduces brain levels of ß-amyloid, ß-amyloid-mediated oxidative damage, and neurotoxicity. This is an 18-month, placebo-controlled study of the efficacy and safety of DHA 2 grams per day (involving a total of 8 visits). Permits concurrent treatment with cholinesterase inhibitors and memantine. (MMSE 14-26) HIC#0610001926
NEUROIMAGING STUDIES
Enrolling
PET Amyloid Imaging in First-Degree Relatives. A very important question is whether ß-amyloid plaques—a hallmark of AD—can be measured in the brains of people who have no symptoms but are at future risk for AD. The purpose of this research is to examine whether ß-amyloid plaques, as measured using PET (Positron Emission Tomography) scanning and the tracer [11C]PIB, are increased in healthy people with a family history of Alzheimer’s disease who also carry the genetic risk factor known as ApoE4. This is a study for individuals between the ages of 50 and 70 who have no memory problems and have at least one first degree relative (brother, sister, mother, or father) with probable Alzheimer’s disease. The study procedures include a medical history and physical, blood and urine samples, memory and cognitive tests, an MRI scan, and a PET scan. Length of participation is approximately 6 months. Subjects will be compensated up to $500 for their time. HIC#0702002301
PET Imaging of the Norepinephrine Transporter in Healthy Subjects and Patients with Adult ADHD. The purpose of this study is to compare norepinephrine transporter (NET) levels between adults with Attention Deficit Hyperactivity Disorder (ADHD) and healthy individuals using PET (Positron Emission Tomography) scanning and the tracer [11C]MRB. In addition, this study examines the NET occupancy after a range of doses of methylphenidate (Ritalin) to illuminate whether this occupancy may play a role in the therapeutic effect of methylphenidate treatment in ADHD. We are currently looking for people aged 18-50 in good health to have a total of three PET scanning sessions. Subjects who complete all procedures will receive up to $1,600. HIC# 0709003102
Closed To Enrollment
Alzheimer’s Disease Neuroimaging Initiative (ADNI). The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a 5-year public-private partnership to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), additional biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD). There are three major goals of ADNI. The first goal is to develop improved methods that will lead to uniform standards for acquiring data on patients with AD, MCI, and elderly controls. The second goal is to create an accessible data repository that describes longitudinal changes in brain structure and metabolism while acquiring clinical, cognitive and biomarker data for validation of further imaging studies. The final goal is to determine those methods that provide maximum power to determine treatment effects in trials involving these patient groups. Cholinesterase inhibitors and Memantine are allowed if stable for at least 4 weeks prior to screening. Ages 55-90 inclusive. Controls: MMSE 24-30; MCI: MMSE 24-30; AD subjects: MMSE 20-26. Length of participation is approximately 2-3 years. HIC#0503027511
GENETICS STUDIES
Enrolling
Apolipoprotein E and Other Genetic Factors in Alzheimer’s Disease. Apolipoprotein E (ApoE) is the major genetic risk factor for AD. The purpose of this research is to determine whether ApoE is related to differences among patients with AD, for example in the rate of progression, associated symptoms, and brain imaging features. We may also study other genes thought to be related to AD or brain function. Subjects participating in other studies in the ADRU may also participate in this study by providing a blood sample for genetic testing. HIC# 0505008171
Please call us at (203) 764-8100 if you would like more information about any of these studies. Interested patients/caregivers are also more than welcome to call us if they are interested in participating in any of our research studies or would like more information.
