| Location |
Multiple sites across the United States |
| Type |
Clinical Trial Network |
| Founded |
2019 (as ACTC); predecessor ADCS established 1991 |
| Funding |
National Institute on Aging (NIA) |
| Website |
nia.nih.gov/actc |
| Focus Areas |
[Alzheimer's Disease](/diseases/alzheimers), Clinical Trials, Therapeutic Development |
| Parent Institution |
[NIH - National Institute on Aging](/institutions/nih-nia) |
The Alzheimer's Clinical Trial Consortium (ACTC) is a national clinical trial network dedicated to accelerating the development of effective treatments for Alzheimer's disease (AD) and related dementias[@nia]. Funded by the National Institute on Aging (NIA), the ACTC provides the infrastructure, expertise, and coordination necessary to conduct large-scale, multi-site clinical trials efficiently and rigorously.
The ACTC represents the next evolution of Alzheimer's clinical research networks, building upon the legacy of the Alzheimer's Disease Cooperative Study (ADCS), which operated from 1991 to 2019. The consortium brings together leading academic medical centers across the United States to create a unified platform for therapeutic development[@alzheimers].
¶ Mission and Objectives
The ACTC's mission is to accelerate the development of effective Alzheimer's disease treatments by:
- Streamlining Clinical Trials: Reducing redundancy and administrative burdens across trial sites
- Standardizing Protocols: Implementing best practices for AD clinical trial design
- Improving Recruitment: Enhancing enrollment strategies to meet recruitment goals
- Data Sharing: Creating harmonized data collection and sharing protocols
- Training: Developing the next generation of AD clinical trialists
The ACTC's predecessor, the Alzheimer's Disease Cooperative Study (ADCS), was established in 1991 as a cooperative agreement between the NIA and academic centers across the United States. The ADCS conducted numerous landmark clinical trials in AD, including:
- Vitamin E and Selegiline trial (1997): One of the first large-scale trials for AD
- Donepezil (Aricept) studies: Supported regulatory approval
- IVIG trial: Investigated intravenous immunoglobulin
- A4 Trial (Anti-Amyloid Treatment in Asymptomatic AD): Pioneered prevention trials in preclinical AD
In 2019, the NIA restructured the ADCS into the Alzheimer's Clinical Trial Consortium, expanding the network and updating its governance structure to meet the evolving needs of AD therapeutic development[@acttc].
¶ Structure and Governance
The ACTC is organized as a distributed network with centralized coordination:
- Clinical Trials Committee: Sets scientific direction and priorities
- Executive Committee: Oversees operations and governance
- Data Coordinating Center: Manages trial data and analytics
The ACTC includes approximately 35-40 leading academic medical centers across the US, including:
- Alzheimer's Disease Research Centers
- Major university medical centers with neurology departments
- Specialized memory disorders clinics
- Disease-modifying therapies: Targeting amyloid, tau, and other pathological proteins
- Symptomatic treatments: Cognitive enhancers, behavioral interventions
- Prevention trials: Interventions in preclinical and prodromal AD
- Repurposing studies: Investigating existing drugs for AD
- Adaptive trials: Flexible designs that allow modifications
- Basket trials: Molecularly-targeted approaches
- Platform trials: Master protocols for multiple treatments
- Digital endpoints: Remote monitoring and digital biomarkers
The ACTC has conducted and continues to support numerous clinical trials, including:
¶ Ongoing and Recent Trials
- Leqembi (lecanemab): Phase 3 trials leading to FDA approval
- Donanemab: Phase 3 TRAILBLAZER-ALZ studies
- Various prevention trials: Trials in cognitively normal individuals with AD biomarkers
- Clarity AD: Leqembi confirmatory trial in early AD
- TRAILBLAZER-ALZ 3: Prevention trial in cognitively normal subjects
- A4 Trial: Anti-amyloid treatment in preclinical AD
- DIAN-TU: Dominantly Inherited Alzheimer's Network Trials
- Generation Studies: Prevention trials in genetic risk populations
- ADCS Azeliragon Trial: Phase 3 study in early AD
- EXERT Trial: Exercise intervention in MCI
The ACTC maintains a robust pipeline of upcoming trials:
| Phase |
Compound |
Target |
Status |
| Phase 3 |
Lecanemab |
Amyloid-β |
Approved |
| Phase 3 |
Donanemab |
Amyloid-β |
Approved |
| Phase 2 |
Semorinemab |
Tau |
Active |
| Phase 1 |
Various |
Multiple targets |
Recruiting |
The ACTC has made significant contributions to the field:
- Accelerated timelines: Reduced time from concept to trial launch
- Improved efficiency: Streamlined operations across sites
- Data harmonization: Standardized outcomes and biomarkers
- Training pipeline: Developed clinical trialists
- Regulatory engagement: Strong relationships with FDA
- Precision medicine: Biomarker-driven enrollment strategies
- Diversity initiatives: Improved representation in clinical trials
- Lecanemab approval: Contributed to FDA approval of the first disease-modifying therapy for early AD
- Biomarker standardization: Established CSF and PET biomarker protocols used worldwide
- Trial design innovation: Pioneered adaptive and platform trial approaches
- Global impact: Supported trials in over 150 sites across 5 continents
¶ Training and Career Development
The consortium invests heavily in training the next generation of AD clinical researchers:
- Clinical Trials Fellowship: 2-year program for early-career investigators
- Summer Institute: Intensive training in AD clinical trial methodology
- Mentorship Program: Pairing junior investigators with experienced mentors
ACTC trainees have gone on to:
- Lead clinical trials at major academic centers
- Serve as principal investigators in industry-sponsored studies
- Contribute to FDA regulatory reviews
- Direct research programs at non-profit organizations
- NIH/NIA: Primary funder and strategic partner
- Alzheimer's Association: Research and advocacy collaboration
- ACTC Sites: 35+ academic medical centers nationwide
- EU-CTI: European Clinical Trials Initiative
- DIAN-TU: Dominantly Inherited Alzheimer's Network
- APOE Consortium: International genetics collaboration
¶ Governance and Leadership
The ACTC is led by distinguished researchers in the field:
- Principal Investigator: Dr. Ronald C. Petersen (Mayo Clinic)
- Co-Investigators: Leaders from partner institutions
- Scientific Advisory Board: External experts in AD research
- Executive Committee: Strategic direction and operations
- Data Safety Monitoring Board: Independent trial oversight
- Publication Committee: Scientific output coordination
The ACTC is positioned to lead next-generation AD trials:
- Combination therapies: Multi-target approaches
- Precision medicine: Genetic and biomarker stratification
- Digital health: Remote monitoring and digital endpoints
- Prevention trials: Intervening before symptom onset
- Diversity and equity: Expanding trial access
- REACH Initiative: Increasing participation from underrepresented populations
- Global Health: Extending trial networks to low-resource settings
- Data Science: AI/ML for trial optimization
¶ Member Sites and Institutions
The ACTC brings together leading academic medical centers across the United States, each contributing unique expertise and patient populations:
| Site |
Location |
Special Expertise |
| University of California, San Diego |
San Diego, CA |
Early-phase trials, biomarker research |
| Massachusetts General Hospital |
Boston, MA |
Tau imaging, clinical outcomes |
| University of Southern California |
Los Angeles, CA |
Latino/Hispanic populations, prevention trials |
| Washington University in St. Louis |
St. Louis, MO |
DIAN-TU, dominantly inherited AD |
| University of Michigan |
Ann Arbor, MI |
Clinical operations, recruitment |
| University of Kentucky |
Lexington, KY |
Rural populations, diverse cohorts |
| Emory University |
Atlanta, GA |
African American populations |
| Stanford University |
Palo Alto, CA |
Technology-enabled trials, digital biomarkers |
| Cleveland Clinic |
Cleveland, OH |
Clinical care integration |
| Mount Sinai |
New York, NY |
Biomarker development, genomics |
- Prevention-focused sites: California Pacific Medical Center, Banner Sun Health Research Institute
- Early AD sites: Multiple sites with expertise in preclinical and prodromal populations
- Diverse population sites: USC, Emory, University of Florida for underrepresented populations
The ACTC supports clinical trials across all phases of development:
- First-in-human studies
- Dose-escalation studies
- Safety and tolerability assessments
- Pharmacokinetic/pharmacodynamic studies
- Dose-finding studies
- Preliminary efficacy assessments
- Biomarker validation
- Proof-of-concept studies
- Pivotal registration trials
- Large-scale efficacy studies
- Comparative effectiveness
- Long-term safety studies
¶ Infrastructure and Resources
The ACTC provides shared infrastructure including:
- ClinicalTrials.gov registration: Standardized trial registration
- EDC systems: Electronic data capture across all sites
- Central laboratory: Standardized biomarker assays
- Imaging core: MRI, PET, CT imaging standardization
- Statistical core: Power calculations, statistical analysis plans
The ACTC has been at the forefront of implementing adaptive trial designs in AD:
- Interim analyses allowing sample size adjustments
- Predictive probability approaches
- Bayesian adaptive methods
- Drop-loser designs eliminating ineffective arms
- Platform trial master protocols
- Multi-arm multi-stage (MAMS) designs
- Biomarker-based enrichment
- Genetic stratification (APOE, TREM2)
- Cognitive reserve adjustments
The ACTC has pioneered Bayesian methods in AD trials:
- Bayesian adaptive randomization: More patients receive potentially effective treatments
- Historical data borrowing: Leveraging prior trial information
- Predictive probability: Early termination decisions
- Subgroup treatment effects: Personalized medicine approaches
Recent ACTC trials incorporate digital health technologies:
- Digital cognitive assessments: Cambridge Neuropsychological Test Automated Battery (CANTAB)
- Wearable devices: Activity monitoring, sleep tracking
- Remote monitoring: Digital biomarkers for disease progression
- Telehealth: Virtual visits, remote consent
The ACTC maintains standardized biomarker collection:
- Amyloid-β (Aβ40, Aβ42)
- Total tau (t-tau)
- Phosphorylated tau (p-tau181, p-tau217)
- Neurofilament light chain (NfL)
- Plasma Aβ (Aβ40, Aβ42, Aβ42/40 ratio)
- Plasma tau (p-tau181, p-tau217, p-tau231)
- NfL, GFAP
- Emerging multiplex assays
- Amyloid PET (Pittsburgh compound B, florbetapir)
- Tau PET (AV-1451, MK-6240)
- Structural MRI (hippocampal volume, cortical thickness)
- FDG-PET (glucose metabolism)
The ACTC has established rigorous validation protocols:
- Assay standardization: Central laboratory processing
- Longitudinal stability: Characterizing within-subject variability
- Clinical validation: Correlation with clinical endpoints
- Regulatory acceptance: FDA/EMA biomarker qualification
¶ Patient Recruitment and Diversity
The ACTC has implemented innovative recruitment approaches:
- Alzheimer's Prevention Registry
- Brain Health Registry
- Local ADRC registries
- Faith-based partnerships
- Community health centers
- Minority-serving institutions
- Social media campaigns
- Online advertising
- Clinical trial marketplace platforms
¶ Diversity, Equity, and Inclusion
The ACTC has prioritized increasing representation:
- Caucasian: ~80%
- African American: ~10%
- Hispanic/Latino: ~7%
- Asian: ~3%
- LATINOS program: Spanish-language outreach
- AFA partnership: African American engagement
- Site selection: Geographic diversity
- Inclusion criteria: Expanding eligible populations
The ACTC maintains active regulatory relationships:
- Regulatory strategy consultation
- Study design feedback
- Biomarker qualification pathways
- End-of-phase 2 meetings
- Pre-phase 3 meetings
- Breakthrough therapy designation support
- Real-world evidence generation
- Label expansion studies
- Registry-based studies
- Parallel scientific advice
- Global trial coordination
- Regulatory harmonization efforts
¶ Data Sharing and Open Science
The ACTC supports open science:
- Qualified researcher access: Controlled access to trial data
- Summary results posting: ClinicalTrials.gov results posting
- Publication of negative results: No publication bias
- Code sharing: Analysis code on GitHub
- AMP-AD: Partnership with NIH Accelerating Medicines Partnership
- NIADS: Data sharing across neurodegenerative disease trials
- GAAIN: Global Alzheimer's Association Interactive Network
¶ Training and Career Development
The ACTC invests in developing the next generation:
- Clinical trial methodology fellowships
- Clinical research methodology degrees
- Sub-specialty training in AD trials
- Junior investigator mentorship
- Protocol development mentorship
- Leadership development
- GCP certification requirements
- Protocol-specific training
- Cognitive assessment certification (ADAS-Cog, CDR)
- Biomarker collection training
¶ Funding and Financial Model
The ACTC receives funding from multiple sources:
| Source |
Percentage |
Focus |
| NIA Grants |
~70% |
Core infrastructure, specific trials |
| Industry |
~25% |
Pharmaceutical company trials |
| Foundation |
~5% |
Prevention trials, special programs |
- Per-patient costs: $15,000-30,000 depending on complexity
- Site startup: $50,000-150,000 per site
- Central operations: $2-5 million annually
- Phase 3 trial costs: $50-100 million total
¶ Landmark ADCS Trials
The ACTC's predecessor conducted numerous pivotal trials:
- Vitamin E and Selegiline (1997): First large-scale AD symptomatic trial
- Donepezil studies: Supported FDA approval of cholinesterase inhibitors
- IVIG (Gammagard): First immunotherapy trial in AD
- A4 Trial: Pioneered preclinical AD prevention trials[@a4trial]
- DIAN-TU: First trials in dominantly inherited AD[@dian]
- Leqembi (lecanemab): Phase 3 Clarity-AD trial leading to FDA approval[@lecanemab]
- Donanemab: Phase 3 TRAILBLAZER studies[@donanemab]
- ACI-35: Phospho-tau vaccine trial
- Multiple prevention trials: Generation studies, EARLY trial
The ACTC is focusing on:
- Combination therapy trials: Multi-target approaches
- Resilience and prevention: Intervention before symptoms
- Precision medicine: Biomarker-guided treatments
- Point-of-care diagnostics: Decentralized trials
- Digital twins: Computational modeling of disease progression
- AI/ML: Predictive enrollment, outcome prediction
- Remote trials: Home-based assessments
- Continuous monitoring: Digital biomarkers
| Metric |
Value |
| Member Sites |
35-40 |
| Trials Conducted |
50+ |
| Patients Enrolled |
15,000+ |
| Annual Budget |
~$30M |
| Publications/year |
100+ |
| Active Trials |
10+ |
- NIA Alzheimer's Clinical Trial Consortium
- Alzheimer's Disease Cooperative Study History
- ACT-TC Overview and Structure
- A4 Trial: Anti-Amyloid Treatment in Asymptomatic AD. Salloway et al. 2014
- Lecanemab for Early Alzheimer's Disease. van Dyck et al. 2023
- Donanemab in Early Alzheimer's Disease. Sims et al. 2023
- DIAN-TU: Dominantly Inherited Alzheimer's Network Trials. Bateman et al. 2020
- Clinical Outcomes in Alzheimer's Disease Trials. Cummings et al. 2022
- Biomarker Development in Alzheimer's Clinical Trials. Jack et al. 2020