Clinical Trials

The following is a list of research studies currently being conducted in the Yale Alzheimer’s Disease Research Unit. Studies actively seeking participants are listed first.

Please call us at (203) 764-8100 if you would like more information about any of these studies. Interested patients and 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.

Treatment Studies

Enrolling

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

Solanezumab for Mild Alzheimer's Disease.
Solanezumab (LY2062430) is an anti-AB IgG1 monoclonal antibody that is directed against the amyloid-β protein. This is an 18-month, placebo-controlled, Phase 3 study designed to test the hypothesis that Solanezumab will slow the cognitive and functional decline of individuals with mild Alzheimer’s disease. Subjects will receive Solanezumab 400 mg or placebo once every 4 weeks as an intravenous infusion (50% probability of receiving active study medication; 22 visits total). 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 brain MRI scanning at the beginning and end of the study. They will also be required to have a florbetapir PET scan at the beginning and end of the study. Permits concurrent treatment with cholinesterase inhibitors and memantine. (MMSE 20-26, inclusive) HIC # 1306012209

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

MK-8931 for Mild to Moderate 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 an 18-month, placebo-controlled, Phase 2/3 study to evaluate the efficacy and safety of MK-8931 in individuals with mild to moderate Alzheimer’s disease. To provide further assessment of the safety and tolerability of MK-8931 prior to allowing enrollment into the Main Cohort, the first group of subjects will enrolled in a Safety Cohort and will be monitored more frequently. Subjects enrolled in the Safety Cohort will be randomized to one of four treatment arms and will be required to have six brain MRIs (75% probability of receiving active study medication). Subjects enrolled in the Main Cohort will be randomized to one of three treatment arms and will be required to have four brain MRIs (67% probability of receiving active study medication). All subjects will have the option of participating in a CSF biomarker. Those in the main cohort will also have the option of participating in a PET imaging substudy. At the end of the 78-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 15 to 26 inclusive). HIC #1204009991

BAN2401 for Early Alzheimer’s Disease.
BAN2401 is humanized IgG1 monoclonal antibody that is directed against the amyloid-β protein with high selectivity for soluble Aβ aggregate species (“oligomers”). This is an 18-month, placebo-controlled, phase 2 study to evaluate safety, tolerability, and clinical efficacy of BAN2401 in individuals with early Alzheimer’s disease, defined as mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s disease. Subjects will receive study drug/placebo by infusion at baseline and every two weeks for a total of 39 infusions. They will be randomized to receive placebo or one of 5 treatment arms of BAN2401 (71% probability of receiving active study medication; 43 visits total). Subjects will be required to have 8 brain MRI scans and may also participate in optional PET and cerebrospinal fluid (CSF) substudies. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE 22-30 inclusive) HIC # 1211011120

LMTM (TRx0237) for Mild to Moderate Alzheimer’s Disease.
Leuco-methylthioninium bis(hydromethanesulfonate (LMTM; TRx0237) is a second-generation tau aggregation inhibitor that may reduce the neurodegeneration associated with the formation of neurofibrillary tangles and thereby slow the progression of this disease. This is a 12-month, placebo-controlled, Phase 3 study to evaluate the efficacy and safety of LMTM in individuals with mild to moderate Alzheimer’s disease. Subjects will be randomized to receive placebo or one of two doses of LMTM (60% probability of receiving active study medication). Subjects will take oral doses of study medication twice daily for 52 weeks (9 visits total). Subjects will be required to have 5 brain MRI scans. Subjects may also participate in an optional PET substudy. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE 14-26 inclusive). HIC # 1303011645

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

Closed To Enrollment

AZD0530 for Mild to Moderate Alzheimer’s Disease.
AZD0530 is thought to work by protecting neurons from the damage caused by the oligomeric form of the beta-amyloid protein. This is an 8 to 9 week, placebo-controlled, Phase 1b study designed to evaluate the safety, tolerability, and brain availability of AZD0530 in patients with Alzheimer’s disease (6-9 visits total). Subjects will be randomized to receive daily oral doses of AZD0530 10-125 mg or placebo daily for up to five weeks (75% probability of receiving active study medication). Subjects will be required to have one brain MRI scan, two FDG-PET scans, and one lumbar puncture provide with study participation. Permits concurrent treatment with cholinesterase inhibitors and/or memantine. (MMSE 16-26 inclusive) HIC # 1303011664

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

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