NCT06911944: ALADDIN

Amyloid Lowering for Alzheimer's in Down's With Donanemab Investigation

Not yet recruiting Phase 4 Last updated 24 November 2025

What this trial tests

Phase 4 trial testing Donanemab in Down Syndrome (DS) in 60 participants. Not yet recruiting.

Timeline

1 August 2026

Primary endpoint
31 December 2028

31 December 2028

Quick facts

Lead sponsor	Michael Rafii, MD, PhD
Phase	Phase 4
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	60
Start date	1 August 2026
Primary completion	31 December 2028
Estimated completion	31 December 2028

Drugs / interventions tested

• Donanemab (DONANEMAB) — full drug profile →
• Placebo

Conditions studied

• Down Syndrome (DS) — all drugs for Down Syndrome (DS) →
• Down Syndrome (Trisomy 21) — all drugs for Down Syndrome (Trisomy 21) →
• Alzheimer Disease — all drugs for Alzheimer Disease →
• Amyloid Beta Protein — all drugs for Amyloid Beta Protein →

Sponsor

Michael Rafii, MD, PhD

Who can join

Adults 35 to 50, any sex, with Down Syndrome (DS) or Down Syndrome (Trisomy 21). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The goal of this clinical trial is to learn if donanemab can reduce levels of amyloid in the brain, and if donanemab is safe and well-tolerated in participants with Down syndrome.

The main questions it aims to answer are: Does donanemab reduce amyloid in the brain? Is donanemab safe and well-tolerated in people with Down syndrome? Researchers will compare donanemab to a placebo (a look-alike substance that contains no drug) to see if donanemab works to reduce levels of amyloid in the brain.

Participants in the study will be 35-50 years old and will be in the study for 12 months. Participants will then stay in the study for an additional 12 months in an long-term extension where all participants will receive donanemab. Participants who had a reduction in amyloid (measured by amyloid brain scan) by the end of the first 12 months will receive placebo for the long-term extension, while participants who did not have an amyloid reduction will receive study donanemab for the long-term extension. Everyone (participants and study staff) will remain blinded to treatment for the duration of the study.

Participants will:

* Have intravenous (IV) infusions of donanemab (or placebo) every 4 weeks
* Visit the clinic once every other month for checkups and tests. These tests will include brain scans (magnetic resonance imaging \[MRI\] and positron emission tomography \[PET\] ), blood draws and memory tests.
* Have a study partner who who can provide information about the participant and can join participant for some of the study visits.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current advances and unmet needs in Alzheimer's disease trials for individuals with Down syndrome: Navigating new therapeutic frontiers.
   Barroeta I, Videla L, Carmona-Iragui M, Fortea J, et al · · 2025 · cited 10× · PMID 40528298 · DOI 10.1002/alz.70258
2. Reviewing the possible connection between cerebral amyloid angiopathy and blood-brain barrier integrity in Down syndrome.
   Valay L, Potier MC. · · 2025 · cited 1× · PMID 41137626 · DOI 10.1002/alz.70814
3. Use of anti-amyloid-β monoclonal antibodies in persons with Down syndrome Alzheimer's disease.
   Farrell C, Saini F, Beidas MM, Ryan NS, et al · · 2026 · PMID 42043831 · DOI 10.1002/alz.71404