Synaptic Therapy Alzheimer’s Research Trial (START)

Alzheimer’s disease is characterized by the accumulation of a substance called amyloid (or Aβ) in the brain, the most toxic forms being 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.

This clinical trial is inviting 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). Participants are 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.

The START website is updated on an ongoing basis as new sites begin screening participants: www.start-study.org 

ACTC Solution

ACTC worked closely with the company that developed this new treatment to design the best study. The Research Participant Advisory Board provided in depth feedback on the study consent form and study name, as well as suggestions on how to make the study more inclusive and accessible to all communities. The ACTC Biomarker Unit is implementing a novel study in some of the START participants measuring new markers in the CSF and blood.