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

JNJ-54861911 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 or cerebrospinal fluid) are at increased risk for cognitive decline and progression to Alzheimer’s dementia. JNJ-54861911 is a 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 4.5-year, placebo-controlled, Phase 2b/3 study designed to evaluate the efficacy of JNJ-54861911 in individuals who are asymptomatic and at risk for Alzheimer’s disease symptoms. During the double-blind period, participants will be randomized to receive study drug (5 mg or 25 mg) or placebo that will be administered orally (67% probability of receiving active study medication). Subjects will have up to 7 brain MRI scans and may have up to 3 PET scans and up to 3 lumbar punctures provided with study participation. HIC# 1608018299

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. 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. Subjects in Group 1 will be randomized to receive either CAD106 or placebo as an intravenous (IV) infusion once every 13 weeks (five in eight chance—or 63% probability—of receiving active CAD106). Subjects in Group 2 will be randomized to receive either CNP520 or placebo as an oral medication taken daily (three in five chance—or 60% probability—of receiving active 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

CNP520 for Individuals at Risk for Alzheimer’s Disease
Clinically “normal” older individuals who are have at least one APOE4 allele may be at a higher risk of developing symptoms of Alzheimer’s disease. CNP520 is an orally active BACE-1 inhibitor that is being tested for safety and efficacy in subjects at risk for the onset of symptoms of Alzheimer’s disease. This is a 5 to 8-year, placebo-controlled, Phase 2/3 study designed to evaluate the safety and efficacy of CNP520 in individuals who have at least one APOE4 allele and are age 60-75 years. Subjects who have only one APOE4 allele will also need evidence of elevated brain amyloid for study eligibility. Subjects will be randomized to receive either 15 mg or 50 mg of CNP520 or placebo as an oral medication taken daily (three in five chance—or 60% probability—of receiving active CNP520). Subjects will be required to have 8-11 brain MRI scans and 1 18F-florbetapir PET scan provided with study participation. (MMSE 24-30, inclusive). HIC# 2000021334

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

LY3314814 for Mild Alzheimer’s Disease
LY3314814 is a BACE1 inhibitor that may impact the production of β-amyloid to slow the progression of Alzheimer’s disease. This phase 3 study includes a 78-week double-blind, placebo-controlled period and a 78-week delayed-start period designed to evaluate the efficacy of LY3314814 in individuals with mild Alzheimer’s disease. During the 78-week double-blind period, participants will be randomized to receive study drug (20 mg or 50 mg) or placebo that will be administered orally (67% probability of receiving active study medication). During the 78-week delayed-start period, participants will receive LY3314814 20 mg or 50 mg. Subjects will have up to 4 brain MRI scans and up to 3 PET scans provided with study participation, along with the option for 7 additional PET scans. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE 20-26, inclusive). HIC# 1605017755

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

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

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

PET Imaging of Synaptic Density in Alzheimer’s Disease
Since synaptic loss is a robust and consistent component of Alzheimer’s disease (AD) pathology, direct measurement of synaptic density could be an important step for understanding disease progression. We recently developed [11C]APP311, a PET tracer for quantitative measurement of a vesicle membrane protein present in virtually all synapses. The purpose of this research is to examine these synapses, as measured using Positron Emission Tomography (PET) scanning and the tracer [11C]APP311, in participants between the ages of 55 and 90 with mild cognitive impairment (MCI) or dementia due to AD, as well as participants without cognitive impairment. The study procedures include medical history and physical exam, blood and urine samples, memory testing, an MRI scan, and up to 3 PET scans. Length of participation is approximately 6 months. Participants will be compensated up to $800 for their time. HIC# 1608018300

Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI 3)
At present, the development of drugs for patients with Alzheimer’s disease is costly and time consuming. The validation of suitable biomarkers that track the progression of the disease and reflect underlying pathology is critical to streamlining this process. This is a multi-center observational research study designed to look at the relationships between clinical, cognitive, imaging, genetic, and biomarker tests in order to understand the full spectrum of Alzheimer’s disease (AD) from its earliest stage. It will enroll 1,070 to 2,000 total participants ages 55–90 (inclusive) across three cohorts: cognitively normal, mild cognitive impairment, and mild AD dementia. Approximately 700-800 of those participants will have also been in the ADNI-2 study. Study participation will last 3-5 years based on cohort (up to 6 visits total). All subjects will undergo MRI scans, up to 8 PET scans, and up to 3 lumbar punctures. They will also have the option to participate in a brain donation program. HIC# 1608018296

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