Low-Dose Radiotherapy for Alzheimer's Disease (LDRT-MIND)

July 3, 2026 updated by: Evan Thomas

Low-Dose Radiotherapy for Alzheimer's Disease: A Phase I/II Open-Label Feasibility and Safety Study (LDRT-MIND Trial)

To evaluate the safety and tolerability of low-dose whole brain radiotherapy (WBRT) delivered as an induction course of 0.3 Gy × 10 fractions (3.0 Gy total) followed by 12 months of monthly maintenance LDRT (0.3 Gy × 10 fractions; 3.0 Gy total) in patients with Alzheimer's disease or dementia with inflammatory components

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥50 years at time of enrollment
  2. Externally confirmed diagnosis by a neurologist or geriatric psychiatrist (at Renaissance Institute, collaborating neurologist Dr. Sherif Makar, MD of Charis Neurology is available for diagnostic consultation) of one of the following: a. Alzheimer's disease (per NIA-AA 2011 or 2018 criteria) b. Frontotemporal dementia with documented inflammatory features c. Dementia with Lewy bodies with elevated inflammatory CSF markers d. Other neurodegenerative dementia with confirmed inflammatory component (elevated CSF IL-6, IL-1β, or TNF-α; or neuroimaging evidence of neuroinflammation)
  3. MoCA score 10-25 at baseline screening (moderate-to-mild cognitive impairment range)
  4. Karnofsky Performance Status (KPS) ≥60 or ECOG Performance Status ≤2
  5. Medically stable and capable of receiving radiation therapy as assessed by the treating radiation oncologist
  6. Reliable caregiver or informant able to accompany the patient to ≥80% of scheduled visits
  7. Written informed consent from patient (if decision-making capacity is preserved) and/or legally authorized representative (LAR); caregiver co-consent required
  8. Life expectancy ≥18 months in the opinion of the treating physician

  9. Ability and willingness to comply with monthly clinic visits for the 12-month maintenance period

    --------------------------------------------------------------------------------------

Exclusion Criteria:

  1. Prior whole brain or partial brain radiotherapy of any dose at any time
  2. Active systemic malignancy requiring concurrent oncologic treatment
  3. Implanted device contraindicated with radiation therapy (pacemaker, cochlear implant, deep brain stimulator, or equivalent)
  4. Brain MRI demonstrating any of the following: (a) more than 4 cerebral microhemorrhages on susceptibility-weighted imaging (SWI) or gradient echo (GRE) sequences; (b) more than 1 area of superficial cortical siderosis; (c) severe white matter disease (Fazekas grade 3); or (d) any macrohemorrhage or hemosiderin-stained lesion >10 mm. These thresholds are adapted from established AD trial imaging exclusion criteria to minimize enrollment of patients with advanced cerebrovascular disease or pre-existing hemorrhagic risk factors.
  5. Known active cerebral amyloid angiopathy-related inflammation (CAA-ri) or amyloid-related beta-angiitis (ABRA), whether confirmed by biopsy, CSF analysis, or neuroimaging features consistent with active leptomeningeal or parenchymal amyloid-related inflammation
  6. Active autoimmune encephalitis in acute phase (patients in stable chronic phase are eligible)
  7. Uncontrolled systemic infection or active sepsis at enrollment
  8. Severe psychiatric comorbidity (active psychosis, active suicidal ideation) impairing protocol compliance or safety assessment
  9. Concurrent enrollment in another interventional trial targeting cognitive decline or neuroinflammation
  10. Pregnancy or lactation; women of childbearing potential must use adequate contraception
  11. Inability to lie flat and still for radiation delivery (approximately 10-15 minutes per session)
  12. MoCA <10 at baseline screening (severe dementia; insufficient cognitive range for endpoint assessment)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Group
Low dose radiotherapy in 10 induction treatments followed by 10 maintenance treatments spread across each month starting at 2 month post- induction
Radiation: Low Dose Radiation Therapy
Low dose whole brain radiotherapy delivered as an induction course of 10 fractions followed by 12 months of monthly maintenance LDRT in 10 fractions starting 2 months post-induction

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety, As Measured By Incidence of Grade 3 or Higher Treatment-Related Adverse Events
Time Frame: From the first induction radiotherapy fraction through 30 days after the final monthly maintenance fraction (acute monitoring period), approximately 13 to 15 months
The primary endpoint is the proportion of participants who experience at least one treatment-related adverse event of Grade 3 or higher, graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events are assessed continuously and attributed to study treatment (induction plus monthly maintenance low-dose whole-brain radiotherapy) by the investigator. Feasibility is defined by an acceptable rate of Grade 3 or higher treatment-related events: 15% or lower during the Phase I lead-in (first 10 participants) and 20% or lower across the full study population (N=50). Safety is monitored continuously using a Bayesian Beta-Binomial model; the study pauses for Data Safety Monitoring Board review if the posterior probability that the true Grade 3 or higher rate exceeds 20% reaches 0.80 or greater.
From the first induction radiotherapy fraction through 30 days after the final monthly maintenance fraction (acute monitoring period), approximately 13 to 15 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive Preservation, As Measured By Change in Montreal Cognitive Assessment (MoCA) Score From Baseline to Month 12
Time Frame: Baseline to Month 12, with MoCA assessed longitudinally across the maintenance period and at a standalone Month 12 cognitive endpoint visit
This secondary endpoint evaluates change in cognitive function measured by the Montreal Cognitive Assessment (MoCA), a 30-point scale on which higher scores indicate better cognition. The measure is the change in MoCA score from baseline to Month 12. The trajectory observed in the study cohort (N=50) is compared against a pooled published historical-control decline rate of 2.5 points per year (Tremont 2022; Julayanont 2014) using a Bayesian longitudinal mixed model for repeated measures with a robust meta-analytic-predictive historical-control prior. The prespecified hypothesis is that participants experience stabilization or a slower rate of MoCA decline than the historical reference. To mitigate practice effects, MoCA is administered on a rotating three-form schedule (Original, 7.1, 7.2), with rater identity and form version locked before prior scores become visible.
Baseline to Month 12, with MoCA assessed longitudinally across the maintenance period and at a standalone Month 12 cognitive endpoint visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Evan Thomas

Investigators

  • Principal Investigator: Evan Thomas, MD, PhD, Renaissance Institute of Precision Oncology and Radiosurgery

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 15, 2026

Primary Completion (Estimated)

May 21, 2029

Study Completion (Estimated)

May 21, 2029

Study Registration Dates

First Submitted

June 13, 2026

First Submitted That Met QC Criteria

July 3, 2026

First Posted (Actual)

July 9, 2026

Study Record Updates

Last Update Posted (Actual)

July 9, 2026

Last Update Submitted That Met QC Criteria

July 3, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LDRT-MIND

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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