# DIAN-TU: Next Generation Prevention Trial

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $6,473,282

## Abstract

PROJECT SUMMARY
 The DIAN-TU was formed to design and manage interventional therapeutic trials and find a treatment that
provides cognitive benefit for those certain to develop autosomal dominant AD (ADAD). The DIAN-TU trial
platform is now fully operational in 6 countries, 24 sites, 3 languages with ~100% completion of all
assessments and ~3% attrition, and has completed enrollment in November 2015 for the first two drugs. Initial
funding for the DIAN-TU trial platform established the infrastructure and operations for executing clinical trials
in ADAD and acknowledged the need for evolution within this platform.
 The DIAN-TU Next Generation Prevention Trial will add a new drug arm to the DIAN-TU trial platform and
implement key design changes that allow the platform to test additional drugs with diverse mechanisms of
action more quickly. Significant innovations and specific aims include implementation of: (1) a planned
cognitive run-in period prior to drug administration to provide greater power to detect drug effects,
(2) self-
administered cognitive testing, (3) pre-defined dose escalation algorithm to safely maximize target
engagement, (4) four plus year cognitive endpoint adaptive trial design for asymptomatic subjects that
includes both early biomarker and later cognitive interims to inform early efficacy or futility, and maximize
power in a limited study population, (5) novel imaging (e.g. Tau PET and
MRI) and cerebrospinal fluid (CSF) measures, and (6) ADAD Disease Progression Model (DPM) to detect
changes in cognition earlier. These innovative approaches promise to accelerate identification of effective
drugs for prevention and treatment of AD.
diffusion basis spectrum imaging
Many disease modifying therapies currently in development target
Aβ, which is believed to be the initiator and earliest change in the AD process. These Aβ therapies may be
most beneficial in the ADAD population and earlier in the disease to delay the onset of dementia. A
fundamental and unresolved question is which target will provide the best cognitive response.
 The NexGen trial design is a multi-center, double blind, randomized, pooled placebo-controlled, four plus
year cognitive composite endpoint registration study of a potential disease modifying therapy in 204
individuals at risk for or with dominantly inherited AD. The primary aim of this study will test the ability of a
beta secretase inhibitor (BACEi) to prevent or slow cognitive decline in 100 asymptomatic (CDR 0) ADAD
mutation carriers in the range of -15 to +10 years with respect to estimated age of symptom onset. A
secondary aim of the study is to slow cognitive decline and progression in 140 CDR ≤1 mutation carrier
subjects. Subjects will receive either drug or placebo with 3:1 randomization for an average of 5.1 years to
determine clinical benefit of the primary outcome of the DIAN-TU cognitive composite and secondary
outcomes including multiple cognitive measures and fluid and imaging biomarkers.

## Key facts

- **NIH application ID:** 10263141
- **Project number:** 5R01AG053267-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** RANDALL J BATEMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $6,473,282
- **Award type:** 5
- **Project period:** 2017-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263141

## Citation

> US National Institutes of Health, RePORTER application 10263141, DIAN-TU: Next Generation Prevention Trial (5R01AG053267-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10263141. Licensed CC0.

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