AHEAD 3-45 is a global multicenter clinical trial aimed at preventing memory loss due to Alzheimer's disease, designed and conducted by the Alzheimer's Clinical Trials Consortium (ACTC) in collaboration with Eisai. Funding is through a public-private partnership with National Institute on Aging (NIA), part of the National Institutes of Health (NIH), Eisai, and several philanthropic organizations. It is led by three academic principal investigators: Dr. Paul Aisen from University of Southern California, and Drs. Reisa Sperling and Keith Johnson from Brigham and Women’s Hospital and Massachusetts General Hospital, Harvard Medical School.
AHEAD 3-45 combines two studies with distinct participant groups but with common screening and recruitment to increase efficiency. More details on each study are below.
We anticipate enrollment for AHEAD 3-45 to begin in the first half of 2020. One way to take steps toward participating in AHEAD 3-45, is to enroll in the Alzheimer Prevention Trials (APT) Webstudy today. The APT Webstudy aims to identify participants who may be good future candidates for AHEAD 3-45. Information on how to register for the APT Webstudy can be found above.
The A3 Study aims to get closer to primary prevention of AD, through preventing amyloid build-up in the brain. The study targets cognitively normal individuals who are currently below the threshold for amyloid elevation on amyloid PET but are at high risk for further Aβ accumulation. The A3 Study is a global, multicenter, double-blind, randomized trial to compare the effects of low dose BAN-2401 vs. placebo, to test whether an anti-amyloid beta antibody targeted at protofibrils can slow brain amyloid accumulation at this very early stage of disease. The A3 Study also measures accumulation of tangle pathology using tau PET and exploratory cognitive outcomes.
The A45 Study targets the preclinical (pre-symptomatic) stage of AD. The study will enroll clinically normal participants (little to no cognitive impairment) who have elevated levels of amyloid in brain and are at high risk for progression to mild cognitive impairment and AD dementia. The A45 Study is a global, multicenter, double-blinded, placebo-controlled, randomized trial of a treatment regimen consisting of an anti-amyloid beta antibody targeted at protofibrils to prevent cognitive decline and delay biomarkers of pathological progression versus placebo. In the active arm, individuals will be treated with high-dose BAN2401 to clear amyloid deposits and Aβ protofibrils from the brain, followed by low-dose BAN2401 to prevent re-accumulation of amyloid. The aim of this study is to slow or prevent decline in cognitive performance.Pls: Paul Aisen, MD, Reisa Sperling, MD, Keith Johnson, MDDuration: 4 yearsNIA/NIH Grant #: R01AG054029 (A3), R01AG061848 (A45)
Alzheimer Prevention Trials (APT) Webstudy
If you are 50 years of age or older, you can monitor your own cognitive health by participating in the Alzheimer Prevention Trials (APT) Webstudy. The APT Webstudy is designed to identify people who may have an increased risk for developing Alzheimer’s disease, using the latest technology to monitor their cognitive performance through regular online memory testing. Volunteers of the APT Webstudy participate at their convenience, anywhere they have access to the internet. APT Webstudy participants benefit by:
- Having their cognitive health assessed over time;
- Being on the ‘fast track’ for relevant clinical trials to prevent Alzheimer’s;
- Making an invaluable contribution to advancing Alzheimer’s research, perhaps helping those in the research field find the first Alzheimer’s survivor; and
- Helping ensure that future generations do not experience Alzheimer’s and its difficult challenges.
The APT Webstudy is being conducted by the University of Southern California Alzheimer’s Therapeutic Research Institute (USC ATRI), funded by NIA.
To participate in the APT Webstudy or to learn more, please visit www.aptwebstudy.org. Those identified from the APT Webstudy to have a potential increased risk for memory loss will be referred to participating TRC-PAD (below) site locations. You do not have to participate in the TRC-PAD in-person study to participate in the online APT Webstudy.Pls: Paul Aisen, MD, Reisa Sperling, MD, Jeffrey L. Cummings, MD, ScDDuration: 5 yearsIRB #: HS-17-00746NIA/NIH Grant #: R01AG053798
Trial Ready Cohort for the Prevention of Alzheimer’s Dementia (TRC-PAD)
Those identified to have a potential increased risk for memory loss caused by Alzheimer’s disease, will be referred from the APT Webstudy (above) to the Trial Ready Cohort for the Prevention of Alzheimer’s Dementia (TRC-PAD) in-person study. The purpose of TRC-PAD is to find as many people as possible (also called a “cohort”) who are interested in participating in clinical trials aimed at discovering treatments that will reduce the risk of developing Alzheimer’s dementia. TRC-PAD will help researchers enroll participants into these trials quickly to allow new treatments to be discovered as soon as possible. Participants do not have to participate in the TRC-PAD study in order to participate in the online APT Webstudy.
TRC-PAD is being conducted by the University of Southern California Alzheimer’s Therapeutic Research Institute (USC ATRI), funded by the National Institute on Aging (NIA), and is non-interventional.
To get involved with the TRC-PAD in-person study, please register and participate in the APT Webstudy first at www.aptwebstudy.org. Those identified from the APT Webstudy to have a potential increased risk for memory loss will be referred to participating TRC-PAD site locations.Pls: Paul Aisen, MD, Reisa Sperling, MD, Jeffrey L. Cummings, MD, ScDDuration: 5 yearsIRB #: HS-17-00746
Life’s End Benefits of Cannabidiol and Tetrahydrocannabinol (LiBBY)
Approximately fifty percent of people diagnosed with Alzheimer’s disease (AD) or other types of dementia will receive hospice care at the end of their life. Of these, over seventy percent will be prescribed psychiatric medications for management of agitation. There are no approved treatments or guidelines to assist clinicians in addressing end of life agitation in dementia. In the absence of appropriate evidence-based guidelines, patients are typically prescribed a combination of anti-psychotics, sedatives, and opiates. These medications often lead to undesirable side effects including confusion, constipation, itching, tremors, and muscle contractions, all of which tend to make the situation even worse, lowering quality of life for patients, and adding burden to their care partners.
Recent research suggests that derivatives of cannabis (some of the chemicals found in marijuana) can be beneficial in controlling agitation and distress without the side effects of medications commonly used to treat agitation. In this project, we have chosen to use a combination of two medications, THC and CBD.
Specifically, this project aims to test the efficacy of an oral combination of two cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), for the treatment of agitation in participants with a diagnosis of dementia who are eligible for hospice and experiencing agitation. We propose a 12-week, phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, with primary outcomes evaluating the efficacy and tolerability of a THC/CBD oral combination at week 2 and week 12. A total daily dose of 8 mg of THC and 400 mg of CBD dissolved in digestible oil will be administered 2 times per day with a maximum of 4 mg of THC and 200 mg of CBD per dose.
The study will recruit 150 participants from 15 clinical trial sites in the United States over a 2-year period. To facilitate recruitment and retention and to monitor long-term safety of the THC/CBD combination, completers of the double-blind study will then have the option to participate in a 6-month, open-label extension study.Pls: Jacobo Mintzer, MD, MBA, Brigid Reynolds, NPDuration: 4 yearsNIA/NIH Grant #: R01 AG068324-01
Synaptic Therapy Alzheimer’s Research Trial
Alzheimer’s disease is characterized by the accumulation of a substance called amyloid (or Aβ) in the brain. The most toxic forms of amyloid are small aggregates of amyloid peptide called oligomers.
This study will investigate whether CT1812, a novel and promising therapeutic candidate can halt or slow the process of Alzheimer’s disease.
CT1812 is a small-molecule drug that has been shown to pass into the brain in high concentrations where it binds to a specific set of proteins on synapses called the sigma-2 receptor complex. The sigma-2 receptor responds to and regulates damage to cells, like that inflicted on neurons by Aβ oligomers during Alzheimer’s disease. When CT1812 is bound to the sigma-2 receptor, previous studies have shown that toxic Aβ oligomers are removed from synapses and are unable to bind again. This mechanism is unique among Alzheimer’s therapeutics in development and may offer an indirect means of addressing the toxic insult of Aβ oligomers, potentially protecting against the damage to and destruction of synapses that is characteristic of neurodegenerative diseases such as Alzheimer’s disease.
In 2022 a nationwide randomized controlled clinical trial will enroll approximately 540 individuals from Alzheimer’s Clinical Trial Consortium (ACTC) sites and sites from other partnering institutions. Participants aged 50 to 85 with mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s disease (MMSE 20-30) who have elevated Aβ (as measured by PET or CSF) will be sought. Participants will be randomized to receive CT1812 or placebo for 18 months. In addition to a battery of cognitive measures, the study will use a variety of biomarkers to evaluate target engagement and assess changes in neurodegeneration and disease progression. This study will leverage the centralized resources, shared expertise, and experienced trial sites of the ACTC to investigate the potential of CT1812 to preserve cognitive function for individuals with early Alzheimer’s disease.Pls: Anthony O. Caggiano, MD, PhD, Christopher van Dyck, MDDuration: 18 monthsNIA/NIH Grant #: R01 AG065248-01
A4 Open Label Extension
Evidence suggests that the process of Alzheimer's disease (AD) begins more than a decade before the clinical stage we now recognize as AD dementia. We have undertaken a trial in clinically normal older individuals with biomarker evidence of AD pathology, the A4 Study. The overall goal of the A4 Study is to test the hypothesis that decreasing "upstream" Aβ burden in the preclinical stages of AD will impact biomarkers of "downstream" neurodegeneration and slow the rate of cognitive decline towards MCI and AD dementia. The A4 Open Label Extension (A4 OLE) of the study allows for active treatment continuation of all participants enrolled into the study until top line study results are available. The A4 Study is a Phase 3 blinded study and is being conducted in partnership with Eli Lilly.Pls: Reisa Sperling, MD, Paul Aisen, MDDuration: until release of primary efficacy results (end of 2022)