Clinical Trials

January 2017

Here is a brief synopsis of clinical research studies available in the Alzheimer’s Disease Research Unit. 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.

Treatment Studies

Enrolling

Aducanumab for Early Alzheimer’s Disease
Aducanumab is a human monoclonal antibody that is administered by intravenous infusion and is directed against the amyloid-β protein. This is a 2-year, placebo-controlled, Phase 3 study designed to evaluate the safety and efficacy of aducanumab in individuals with early Alzheimer’s disease (33 clinic visits). Participants will be randomized to receive study drug or placebo that will be administered by intravenous infusion once four weeks (20 infusions; 67% probability of receiving active study medication). Subjects will have 8 brain MRI scans and one PET scan provided with study participation. Subjects may also participate in an optional PET substudy and an optional cerebrospinal fluid substudy. After the 2-year placebo-controlled period, participants will have the option of entering a 2-year long-term extension of the study. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE 24-30, inclusive). HIC #1505015817

Crenezumab for Prodromal to Mild Alzheimer’s Disease.
Crenezumab is a humanized monoclonal antibody that binds to all potentially toxic forms of Aβ, including monomers, oligomers, and fibrils. Because crenezumab is a human IgG4 backbone antibody, it has reduced Fcγ receptor binding affinity compared with human IgG1 or IgG2, which may result in a more favorable safety profile. This is a 2-year, placebo-controlled, Phase 3 study designed to evaluate the safety and efficacy of crenezumab. Participants will be randomized to receive study drug or placebo that will be administered by intravenous infusion every 4 weeks (50% probability of receiving active study medication). Subjects will have 7 brain MRI scans, up to 3 PET scans, and up to 3 lumbar punctures provided with study participation. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE ≥ 22). HIC# 1601017095

CAD106 and CNP520 for Individuals at Risk for Alzheimer’s Disease.
Clinically “normal” older individuals who are homozygous for APOE4 are at particularly high risk of developing symptoms of Alzheimer’s disease. CAD106 is an active vaccine against amyloid-β that is administered by intramuscular injection. CNP520 is an orally active BACE-1 inhibitor that is taken orally. This is a 5 to 8-year, placebo-controlled, Phase 2/3 study designed to evaluate the safety and efficacy of CAD106 and CNP520 in individuals who are APOE4 homozygotes age 60-75 years. The study is currently enrolling Cohort I, in which subjects will be randomized in an 8:3 ratio to receive either CAD106 or placebo as an intramuscular injection every 13 weeks (62% probability of receiving active drug). No subjects are currently being assigned to CNP520. Subjects will be required to have 7-10 brain MRI scans and 2 18F-florbetapir PET scans provided with study participation. (MMSE 24-30, inclusive). HIC# 1601017111

Solanezumab for Individuals at Risk for Alzheimer’s Disease.
A stage of “preclinical Alzheimer’s disease” has recently been defined based on biomarker evidence of amyloid-β pathology before the stage of clinical symptoms. Clinically “normal” older individuals with elevated Aβ pathology (by PET scan) are at increased risk for cognitive decline and progression to Alzheimer’s dementia. Solanezumab (LY2062430) is an anti-AB IgG1 monoclonal antibody that is directed against the amyloid-β protein. This is a 3-year, placebo-controlled, Phase 3 study designed to test the hypothesis that Solanezumab will slow cognitive decline in individuals with preclinical Alzheimer’s disease. Subjects will receive Solanezumab 400 mg or placebo as an intravenous (IV) infusion once every 4 weeks (50% probability of receiving active study medication). Subjects who complete this study may be eligible to receive Solanezumab as part of an additional open-label extension study. Subjects will be required to have 4 brain MRI scans and 2 florbetapir PET scans provided with study participation. Subjects can also participate in 2 optional lumbar punctures during the study. HIC #1311013008

MK-8931 for Prodromal Alzheimer’s Disease.
MK-8931 is an oral molecule of β-site amyloid protein cleaving enzyme (BACE1) inhibitor with the potential to inhibit the synthesis of β-amyloid and thereby to slow the clinical progression of Alzheimer’s disease. This is a 24-month, placebo-controlled, Phase 3 study to evaluate the efficacy and safety of MK-8931 in individuals with prodromal Alzheimer’s disease. Subjects will be randomized to receive one of two active dose arms of MK-8931 or placebo for 24 months (67% probability of receiving active study medication). Subjects will be required to have five brain MRIs and one PET scan. All subjects will have the option of participating in a PET imaging substudy involving an additional PET scan. Subjects will also have the option of participating in a lumbar puncture substudy. At the end of the 104-week treatment period, all subjects who have completed the study may be eligible for enrollment in an open-label extension study. Permits concurrent treatment with cholinesterase inhibitors and memantine. (MMSE ≥ 24 at screening). HIC #1309012771

Intranasal Insulin for Mild Cognitive Impairment and Mild Alzheimer’s Disease.
Insulin resistance, reduced cerebrospinal fluid insulin levels, and reduced brain insulin signals have been found in individuals with Alzheimer’s disease, suggesting that a therapy aimed at correcting these deficiencies may improve cognition and slow Alzheimer’s disease pathogenesis. This is a Phase II/III, double blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of intranasal insulin in approximately 240 individuals with amnestic mild cognitive impairment or mild Alzheimer’s disease. Subjects will be randomly assigned to receive 20 IU Humulin® R U-100 or placebo, administered intranasally (as a nasal spray), twice daily for 12 months (50% probability of receiving active study medication), followed by 6 months in which all subjects will receive intranasal insulin (11 visits total). Subjects will be required to have 2 brain MRI scans and 2 lumbar punctures provided with study participation. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE ≥20). HIC #1309012698

Methylphenidate for Apathy in Dementia.
Apathy is one of the most prevalent and challenging neuropsychiatric symptoms in Alzheimer’s disease. Convergent evidence has suggested that apathy in Alzheimer’s disease is related to disruptions in the brain’s dopaminergic system, and two small pilot trials have suggested a benefit of methylphenidate for this syndrome. This is a 6-month, placebo-controlled, phase 3 study to examine the efficacy and safety of methylphenidate as treatment for clinically significant apathy in individuals with Alzheimer’s disease (7 clinic visits). Subjects will be randomized to receive study drug or placebo twice daily for 6 months (50% probability of receiving active study medication). Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE 10-28, inclusive). HIC #1503015481

Aerobic Exercise for Mild Cognitive Impairment.
This is an 18-month, Phase 3, randomized study designed to evaluate the efficacy of aerobic exercise in individuals with mild cognitive impairment (5 clinic visits). Participants will be randomized to moderate/high intensity aerobic training or stretching/balance/range of motion training (50% probability of being assigned to each training condition). Subjects will exercise at local YMCAs four (4) times per week for 18 months. During the first 12 months of the study, two of the four weekly sessions will be supervised by a study-certified YMCA trainer. In the final 6 months, participants will continue to complete their assigned exercise program at the YMCA without supervision. Subjects will have two (2) brain MRI scans provided with study participation. Subjects may also participate in an optional cerebrospinal fluid substudy (2 lumbar punctures). Permits concurrent treatment with cholinesterase inhibitors. (MMSE ≥ 24). HIC1605017787

Gantenerumab or Solanezumab for Individuals at Risk for and with Dominantly Inherited Alzheimer’s Disease.
Mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) are associated with autosomal dominant Alzheimer’s disease. This study targets individuals who are either known to have a disease-causing mutation or who are at risk for such a mutation (the child or sibling of a proband with a known mutation) and unaware of their genetic status. Gantenerumab and solanezumab are monoclonal antibodies that are directed against the amyloid-β protein. This is a 2-year, double-blind, placebo-controlled, Phase II/III study designed to assess the safety, tolerability, and biomarker efficacy of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Subjects will be randomized to receive gantenerumab 225mg, solanezumab 400 mg, or placebo as a subcutaneous (SC) injection or intravenous (IV) infusion once every 4 weeks for 100 weeks (35 visits total). Subjects who do not carry a disease-causing mutation will be assigned to the placebo group within each treatment arm. Subjects who do carry such a mutation will be randomized in a 3:1 ratio to receive the active drug (solanezumab or gantenerumab) (75% probability of receiving active drug; 25% probability of receiving placebo). Subjects and research staff will remain blinded to the results of genetic testing and also to treatment assignment. Subjects will be required to have 9 brain MRI scans, 8 PET scans, and 3 lumbar punctures during the study. Permits concurrent treatment with cholinesterase inhibitors and memantine. HIC #1308012526

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

Glutamate Receptor Imaging in Individuals with and at Risk for Alzheimer’s Disease.
Since amyloid beta (Aß) seems to have a key role in the pathogenesis of Alzheimer’s disease, understanding how Aß oligomers interact with neurons in the brain to trigger downstream damage is of great importance. One way in which Aß oligomers seem to damage neurons is through activation of the metabotropic glutamate receptor subtype 5 (mGluR5). The purpose of this research is to examine whether mGluR5, as measured using Positron Emission Tomography (PET) scanning and the tracer [18F]FPEB, are decreased in subjects with mild cognitive impairment (MCI) or Alzheimer’s dementia. This is a study for individuals between the ages of 55 to 90 years old that have MCI, AD or no memory problems. The study procedures include medical history and physical exam, blood and urine samples, memory testing, an MRI scan and 2 PET scans. Length of participation is approximately 2-3 months. Participants will be compensated up to $750 for their time. HIC #1410014799

Caregiver Support Group

In addition to our clinical research studies, we offer a free monthly support group for caregivers of AD patients, whether or not they are participating in our research studies. Interested caregivers can call (203) 764-8100 and ask for Susan.

Closed To Enrollment

Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI-2)
The Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI-2) is a public-private partnership to determine the relationships among the clinical, cognitive, imaging, genetic, and biochemical biomarker characteristics of the entire spectrum of Alzheimer’s disease, as the pathology evolves from normal aging through very mild symptoms, to mild cognitive impairment (MCI), to dementia. There are four major goals of ADNI-2. The first goal is to determine and define those biomarkers which best predict future cognitive decline and conversion to MCI/dementia at the various stages of the progression from normal cognition to dementia. The second goal is to determine and define those biomarkers that best serve as outcome measures to quantify the rate of progress at the various stages from controls to dementia. The third goal is to improve clinical trials by developing various clinical trial protocol scenarios, which use clinical, cognitive, and biomarker measures as selection criteria, as covariates, and as outcome measures, with maximum statistical power to detect treatment effects. The final goal is to perform pathological examination on brains obtained by autopsy to validate the antemortum diagnoses. Length of participation is approximately 6 years. All subjects will be required to undergo lumbar puncture for CSF protein analysis. HIC#1011007597

Genetic 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